pdf version - Helmholtz Zentrum München

Transcription

2012
– 13
BIENNIAL REPORT
YOUNG
SCIENTISTS
TALENT
MANAGEMENT
3 YEARS OF
HELENA
RESEARCH
HIGHLIGHTS
Junior research groups
as opportunity for
young researchers
Specific training
for science and
administration
International success
model Helmholtz Graduate School Environmental Health
Selected publications
from the research
programs
At a
glance.
Helmholtz Zentrum München is currently organized in 39 research institutes
and independent units, which are linked via programs and topics. The Center
has various technology platforms and central service units. In order to
facilitate the transfer of results from basic research into medical applications,
scientists of Helmholtz Zentrum München collaborate closely in translational
centers and clinical cooperation groups with medical partners at Munich’s
universities and hospitals.
22
joint appointments with the
Munich elite
universities
39
institutes and
independent
research units
2
information
services i
328 doctoral students
2234 employees
150
18 spin-offs since 1997
1062
publications in
international
journals 2012
1178
publications in
international
journals 2013
3
translational
centers
patent families
224
million
euros
finance volume 2013
11
clinical
cooperation groups
19
junior research
groups
63
trainee places
in 8 professions
3 Biennial Report 2012-2013
CONT ENTS
CONT ENTS
4 5 Table of Contents
6EDITORIAL
50RESEARCH IN SCIENTIFIC PROGRAMS
77
Faster Production of Disease Models
100
INNOVATION AND TRANSLATION
Promotion of Young Scientists at Helmholtz Zentrum
München – a Success Model
Major Common Diseases and the Role of Genes and
the Environment
Programs at the Center and their integration into the
research areas of the Helmholtz Association
78
Human Glial Cells Can Be Reprogrammed
79
Trnp1 Regulates Expansion of Mammalian
Cerebral Cortex
From Basic Research to Applications
Examples of promising approaches for therapy
and prevention
80-81
How Roquin Family Proteins Control T Cells
82-83
Personalized Leukemia Therapy Appears within Reach
84-85
Further Decryption of the Epigenetic Code
106-107 Spearhead of Diabetes Prevention
Florian Haupt, Ruth Chmiel
86
Intellectual Disability Is Caused by
Spontaneous Mutation
108
87
New Insights into the Genetic Mechanisms
of Red Blood Cell Formation
8-15
TIMELINE 2012–2013
Overview of events at the Center
52
INTERVIEWS WITH THE MANAGING DIRECTORS
IMPORTANT RESULTS 2012/2013
We present selected examples from the
2240 publications of the last two years
16-27
Challenges and Perspectives
Günther Wess, CEO, Nikolaus Blum, CFO, and
Alfons Enhsen, CTO, comment on the future
development of Helmholtz Zentrum München
RESEARCH HIGHLIGHTS
54-55
Brain Signal Regulates Body Weight
56
Hormones against Metabolic Syndrome
57
Hormone Duo Promotes Loss of Fat Reserves
58
Predictive Biomarker for Gastric Bypass
88-89
DNA Methylation Plays Important Role
in Human Metabolism
104-105 Antipsychotic Drugs Tested Against Malignant
Lymphomas
Daniel Krappmann
TALENT MANAGEMENT
Qualification Training at the Center
Strategic personnel management develops target
group-oriented employee competence
28
MAIN THEME:
PROMOTION OF YOUNG SCIENTISTS
30-31
Countries of Origin of HELENA Doctoral Students
59
Evolution of Energy Metabolism
90
Detecting the Identities of “Unknown Metabolites”
32-35
Three Years of HELENA
Doctoral training plus leadership skills
60-61
Biomarkers of Pre-diabetes
91
Two Imaging Modalities Better Than One
36-37
38-39
Portraits of Junior Research Groups
We present six of the 19 junior research groups
at Helmholtz Zentrum München
62
Role of Genetics in Type 2 Diabetes Pathogenesis
92-93
Lifestyle Factors affect Metabolite Profile
63
Relationship between PTSD and Type 2 Diabetes
94-95
Bioinformatics for Stem Cell Research
Insights into the World of Mitochondria
Fabiana Perocchi 64-65
Breastfeeding Reduces Risk of Type 2 Diabetes
96
Mapping of the Barley and Bread Wheat Genomes
66
Air Pollution Promotes Insulin Resistance
97
Casting Light on the Evolution of Nightshades
40-41
Peacekeeping Troops of the Immune System
against Type 1 Diabetes
Carolin Daniel
67
Type 1 Diabetes Is Predicted by Autoantibodies
98-99
How Roots Branch Out
68
Progression of Type 1 Diabetes
42-43
Communication Factors under Surveillance
Stefanie Eyerich
69
Infections Increase Type 1 Diabetes Risk
44-45
Searching for the Origin
Micha Drukker
70
Interplay of Cytokines in Asthma
126ORGANIZATION
71
More Risk Genes for Allergies
46-47
Proteins under the Hammer
Tobias Madl
72-73
Cost of Medical Care in Early Stages of COPD
48-49
Signals for the Protection of Plants
Corina Vlot-Schuster
74-75
Key to Neurogenesis
76
Oligodendrocytes and Multiple Sclerosis
112-113 Recruiting and Promoting Talent in Science
Administration
Barbara Ferwagner, Theresia Schmitt, Uwe Bott
114
FACTS & FIGURES
Administrative Statistics for 2012 and 2013
Increase in number of staff and successful
grant acquisition
116-117Staff
118-119 Finances 2012
120-121 Finances 2013
122-125 Project Funding and Research Cooperations
Research Units, Management and Advisory Bodies
Research structure and overview of contact
persons and addresses
128-131 Institutes, Departments, Research Units
and Translational Units
132-133Organization
EDITORIAL
EDITORIAL
6 7 Promotion of Young Scientists
at Helmholtz Zentrum
München – a Success Model
Helmholtz Zentrum München has consolidated its position as one of the world’s leading
institutions in the field of health and the environment. In summer 2013 this was the
assessment of the expert review for the third period of program-oriented funding,
which provides the framework for our scientific work. In its review report, the panel of
international experts commended the Center for its outstanding research achievements
and strategic positioning. In addition, the reviewers specially commended the Center’s
efforts to promote young scientists. In particular, they pointed to the Helmholtz Graduate
School Environmental Health (HELENA), established only three years ago together with
Technische Universität München and Ludwig-Maximilians-Universität, as an international
success model. Currently, approximately 330 young people are working under the
umbrella of HELENA in interdisciplinary teams toward their PhD degrees and are
acquiring additional skills for future leadership positions in science and industry.
As a major theme in this biennial report, we present examples of our successful
training program for young scientists. Read on page 32 how doctoral students use
the opportunities of the Helmholtz Graduate School Environmental Health to begin
their academic or professional careers.
Another focus of the promotion of young scientists at Helmholtz Zentrum München is on
the appointment of talented young researchers to head their own junior research groups.
Equipped with their own budgets and with responsibility for their own staff, the
researchers can establish themselves internationally in their subject area within a
period of five years. In 2012 and 2013, 13 junior research groups were launched.
Altogether, there are 19 junior research groups at the Center, 13 of which are headed
by women. Seven of these are funded by Starting Grants of the European Research
Council. Starting on page 38 we present six junior research groups. At the same time,
each portrait stands for a topic of the research programs of the Center.
At the end of 2013, the Center closed a gap in its strategic concept to promote young
scientists with the first call for applications for an international postdoctoral program.
Up to 16 excellent young scientists will develop and implement their personal career
plan over the course of three years, within the framework of this program and with the
support of scientific mentors and personal coaches.
An important component of talent management at Helmholtz Zentrum München is
the promotion of well-trained science administrators, who serve as bridge between
the needs of the research and the requirements of the administration. Oriented on the
strategic objectives of its research, the Center offers its young professionals in science,
administration and infrastructure a wide range of qualification opportunities. On page
112 you can read how Helmholtz Zentrum München promotes talented young people
in science administration.
Of course, the focus of our work is on successful research and the publication of research
results in international journals. Both the number of publications and their impact
ranking have risen steadily in recent years. In 2012, 1062 publications with 6298 impact
points resulted from research at the Center. In 2013 the publication output increased
to 1178 publications and 7568 impact points. Since 2005 the Center has nearly doubled
the number of its publications and has tripled its impact factors. As highlights of the
Center’s scientific work, we present 34 selected publications starting on page 54.
Research at Helmholtz Zentrum München has successfully met the criteria of scientific
evaluation. In doing so, the Center has never lost sight of its overarching objective:
to contribute to a better understanding of gene-environment associated diseases and
to the development of new therapies – especially for widespread common diseases
such as diabetes, lung diseases and allergies. To ensure that progress in knowledge
rapidly benefits society, translational research and innovation are key elements of our
strategy. Two examples of particularly promising approaches in cancer treatment and
for the prevention of type 1 diabetes can be found on page 104.
In 2013 Helmholtz Zentrum München achieved outstanding results in the review of its
content and strategic development as well as its repositioning within the framework of
program-oriented funding. Our task in the coming years will be to retain this position
and to expand it further. Managing Directors Prof. Dr. Günther Wess, Dr. Nikolaus Blum
and Dr. Alfons Enhsen explain in interviews starting on page 16 how we shall approach
and master this task and describe the challenges that may lie ahead.
The Board of Directors would like to take the opportunity here to express its thanks
to all employees of the Center and to the members of the Supervisory Board and the
Scientific Advisory Board. All have contributed to the successful positioning of the
Center internationally and to strengthening the Center for the future.
The Editors
T IMELINE 2012
T IMELINE 2012
8 9 Timeline 2012
JANUARY 1st
JANUARY 26th
MARCH 27th
Good Clinical Practice: The Center
establishes an internal policy for the
production of clinical trial samples
and for studies that are carried out
together with clinical partners.
The Center expands allergy research:
Under the direction of Prof. Dr.
Carsten Schmidt-Weber – who at the
same time holds the Chair of Molecular Allergology and Environmental
Research at Technische Universität
München – the newly founded Institute of Allergy Research is launched.
JANUARY 3rd
FEBRUARY 4th
More intensive collaboration with
INSERM: Researchers from Helmholtz
Zentrum München and the French
Institut National de la Santé et de
la Recherche Médicale (INSERM)
coordinate projects within the graduate
program “Lung Biology and Disease”.
JANUARY 21st
Outstanding achievement for epidemiologist at the Center: Dr. Jakob
Linseisen places second in Laborjournal’s publication ranking of most
cited German scientists in the field of
nutrition research.
JANUARY 25th
Lung Information Service at the
Center receives ARTs and AIR
AWARD: The award, conferred by the
AtemWeg Foundation and Münchner
Bank for special projects in lung
research, commemorates the artist
Christoph Schlingensief, who died of
lung cancer.
Presentation in Berlin of collaborative lung research success: The
Parliamentary State Secretary in the
Federal Ministry of Education and
Research Dr. Helge Braun and the
spokesperson of the German Center
for Lung Research, Prof. Dr. Werner
Seeger, present novel approaches
to treat lung diseases. Photo: Ingo
Kniest
APRIL 12th
McCulloch and Till Award for Dr.
Timm Schroeder: The head of the
independent Department of Stem
Cell Dynamics at Helmholtz Zentrum
München is awarded the prize of the
International Society for Hematology
and Stem Cells for Young Scientists.
Exploring the workplace: On nationwide “Girls' Day”, 50 school students
gain insight into scientific work at
Helmholtz Zentrum München.
Three prizes for diabetes research at
the Center: At the annual meeting of
the German Diabetes Society Prof. Dr.
Matthias Tschöp receives the Werner
Creutzfeldt Prize, which is endowed
with 10 000 euros. Dr. Christiane
Winkler receives the Ernst Friedrich
Pfeiffer Prize, likewise endowed with
10 000 euros, and Dr. Maren Pflüger
receives the Silvia King Award for
achievements in clinical diabetology.
JUNE 15th
Experts answer questions: The
second patient forum of the Lung
Information Service informs about
childhood bronchial asthma at the
Comprehensive Pneumology Center.
MAY 3rd
The Helmholtz Research School of
Radiation Sciences is established: The
new graduate school in a joint endeavor
with the two Munich universities offers
places for 25 PhD students and is part
of the Helmholtz Graduate School
Environmental Health (HELENA).
FEBRUARY 13th
Focus on aerosols and health: To
investigate the effects of anthropogenic particulate matter, Helmholtz
Zentrum München, the University of
Rostock and six other international
partners join together to form the
Helmholtz Virtual Institute of Complex Molecular Systems in Environmental Health (HICE).
MAY 19th
MAY 2nd
FEBRUARY 1st
Personalized therapies for diabetes:
Helmholtz Zentrum München participates in the DIRECT project, which is
funded by the Innovative Medicines
Initiative (IMI) with 45 million euros.
APRIL 26th
The Central Energy Facility celebrates
its topping out ceremony: With the
expansion of its utility infrastructures, the Center creates important
conditions for the development of its
Neuherberg research campus.
First official visit to the Zugspitze: The
Bavarian State Minister for Health and
the Environment Dr. Marcel Huber
informs himself in the environmental
research station Schneefernerhaus
about the contributions of Helmholtz
Zentrum München to the European
Virtual Alpine Observatory.
Successful completion of apprenticeship: The biology laboratory assistants
Bianca Vogel, Sandra Lubos and
Kristina Steigerwald have successfully
completed their three-year vocational
training. The office administrators
Franziska Kölbl and Evelyn Thiel as
well as warehouse logistics specialist, Michaela Laumeyer have also
completed their apprenticeships with
top grades.
JULY 10th
Setting the course for the future: The
Scientific Advisory Board endorses
the Center’s strategies and concepts
of its environmental health portfolio,
public health and personalized medicine as well as their inclusion into
the program-oriented funding of the
Helmholtz Association (POF III).
JULY 13th
Intensified cooperation: Under the
leadership of its president Prof.
Chunli Bai, a delegation of the Chinese
Academy of Sciences informs itself
about possibilities for expanding
partnerships with Helmholtz Zentrum
München.
Alexander von Humboldt Professorship awarded to Matthias Tschöp:
Federal Research Minister Dr. Annette
Schavan presents the most highly
endowed international award for research in Germany to the director of
the Institute for Diabetes and Obesity
and chair of Metabolic Diseases at
Technische Universität München.
Value creation strengthened: In addition to early-stage projects with value
creation potential, the Department of
Innovation Management, headed by
Dr. Annette Janz, is now also responsible for the patenting and commercialization of innovative know-how.
JUNE 25th
MAY 15th
APRIL 19th
FEBRUARY 17th
Outstanding ranking: The epidemiologist Dr. Joachim Heinrich is ranked
12th in the world among most cited
authors of asthma publications in the
field of lung and respiratory research
and 2nd among the German-language
authors after the former director of
the Institute of Epidemiology, Prof.
Dr. Dr. H.-Erich Wichmann.
JULY 1st
Green light for the specimen bank:
The Supervisory Board approves the
establishment and operation of the
biorepository for the National Cohort
on the Neuherberg research campus.
JULY 15th
JUNE 29th
Diabetes institutes in Garching opened:
Until the completion of the diabetes
building in Neuherberg, the Institute
for Diabetes and Obesity and the
Institute of Diabetes and Regeneration
Research are located on the Garching
Business Campus.
Investigation of the mechanisms of
T cell tolerance: The Research Unit
Molecular Immune Regulation,
headed by Dr. Vigo Heissmeyer,
begins operations.
T IMELINE 2012
T IMELINE 2012
10 11 Timeline 2012
AUGUST 1st
JULY 18th
NOVEMBER 14th
New trends in pulmonary medicine:
The second Munich Lung Conference
begins under the auspices of the Comprehensive Pneumology Center (CPC).
Launch of international competition
for Health and Environment Funding:
The Center funds internal projects on
environmental health problems in the
fields of allergies, the microbiome
and health as well as nanoparticles
with up to 180 000 euros per year.
OCTOBER 22nd
Start of research campus: 50 children
of staff take part in two-week holiday
research program for kids on campus.
AUGUST 14th
The Department of Environmental
Sciences begins work: The merger of
seven research units contributes to the
synergistic effects of environmental
and health research at the Center.
OCTOBER 4th
The challenge of obesity: Within
the framework of the World Health
Summit in Berlin, CEO and Scientific
Director Prof. Dr. Günther Wess moderates the discussion of renowned
scientists.
NOVEMBER 5th
Now a total of eight ERC Starting
Grants at the Center: The European
Research Council (ERC) awards a 1.5
million euro grant to Prof. Dr. Gil Gregor
Westmeyer of the Institute of Biological and Medical Imaging and the
Institute of Developmental Genetics
to develop new methods of imaging
molecular processes in the brain.
Epigenetic research receives VdFF
Research Award: The Association of
Friends and Sponsors (VdFF) awards
a prize for interdisciplinary cooperation to a paper which appeared in
Science in 2012 on the function of
cell memory.
AUGUST 28th
NOVEMBER 6th
B2RUN corporate running competition
in Munich: 168 runners from Helmholtz Zentrum München take part in
the sports event in the Olympia Park.
Beyond Big Data: With Clueda AG, a
new spin-off company from Helmholtz
Zentrum München is launched. It
develops software tools to strongly
increase applicable knowledge and to
read complex situations quickly.
Graduate Students' Day: Prof. Dr.
Erwin Neher, Nobel Laureate in 1991,
holds a Career Lecture.
JULY 23rd
SEPTEMBER 14th
JULY 19th
Diabetes Information Service online:
Under www.diabetesinformations
dienst-muenchen.de the Center makes
information about diabetes available
to the general public.
Balancing career and family: The first
parent-child room for short-term care
needs is opened on campus.
NOVEMBER 13th
Campus Park takes form: With
terrain modeling, work begins on the
two-hectare meeting and recreation
space.
JULY 24th
Top marks for the administration:
A nine-member panel of external
experts presents its results of the
review of planning, managing and
support processes to the staff of the
Center.
NOVEMBER 12th
MELODI Award for Dr. Kristian Unger:
The scientist of the Research Unit of
Radiation Cytogenetics receives in
Helsinki the Multidisciplinary European
Low Dose Initiative Prize, which is
endowed with 4000 euros.
SEPTEMBER 20th
Development of young scientists is
strengthened: The Helmholtz Association announces funding of two new
junior research groups led by Dr.
Stefanie Eyerich and Dr. Claudia Plant.
NOVEMBER 23rd
Strategic alliance against obesity and
diabetes: Helmholtz Zentrum München
and Sanofi Aventis arrange a research
alliance for new targets and screening
methods to develop innovative therapy
approaches.
NOVEMBER 26th
HICE Biomobile starts on first measuring campaign: At four European
stations, scientists of Helmholtz
Zentrum München, the University of
Rostock and their partner institutions study the effects of particulate
matter on lung cells.
DECEMBER 10th
Rapid publication of research results:
Helmholtz Zentrum München and the
German Center for Diabetes Research
at Campus Neuherberg are partners in
the publication of the newly established open access journal Molecular
Metabolism.
T IMELINE 2013
T IMELINE 2013
12 13 Timeline 2013
JANUARY 1st
Coordinating role for the research
field of Health: the CEO and scientific director of the Center, Prof. Dr.
Günther Wess, takes office as scientific vice president of the Helmholtz
Association and coordinator for the
research field of Health.
JANUARY 3rd
Helmholtz researchers appointed to
Radiation Protection Commission:
Prof. Dr. Werner Rühm, head of the
research group Personal Dosimetry of
the Institute of Radiation Protection,
belongs to the committee Radiation
Risk and Dr. Werner Kirchinger, company and fire department physician
and head of the Regional Radiation
Protection Center, belongs to the
committee Emergency Response.
JANUARY 8th
JANUARY 15th
MARCH 1st
MARCH 21st
The Center expands its diabetes
research capacity: The official opening
of the Institute of Diabetes and Regeneration Research, directed by Prof. Dr.
Heiko Lickert, takes place in Garching.
Lickert also holds the Chair of Diabetes
Research/ Beta Cell Biology of Technische Universität München.
Gain for lung research: Prof. Dr. Jürgen
Behr assumes the Chair of Pneumology
at Ludwig-Maximilians-Universität
München and becomes Director of
Clinical Pneumology at the Comprehensive Pneumology Center of Helmholtz
Zentrum München, the LMU University
Hospital and Asklepios Specialist
Clinics in Munich-Gauting.
Review successfully completed:
Reviewers commend international
visibility and high strategic value of
"Sustainable Plant Production" and
"Sustainable Water Management",
two topics coordinated by the Center
in the POF program "Terrestrial
Environment".
JANUARY 23rd
JANUARY 30th
Vocational training completed: Michael
Opitz, Willi Grätz, Markus Fischer and
Alexander Felber successfully complete
their final examination to become
biology laboratory technicians.
Development of the microscope of
the future: The Federal Ministry of
Education and Research promotes the
research cooperation ‘Tech2See’ of the
Institute of Biological and Medical
Imaging of Helmholtz Zentrum
München together with ZEISS and
iThera Medical GmbH.
Event to inform patients: 250 participants attend the first Patients‘ Day of
the Diabetes Information Service concerning the disease diabetes mellitus.
MARCH 19th
FEBRUARY 14th
Joining forces for personalized
medicine: As first German research
institution, Helmholtz Zentrum
München joins the Personalized Medicine Coalition (PMC), an international
consortium of research, industry and
patient organizations.
FEBRUARY 20th
Cooperation partners of the Center
honored with Helmholtz International Fellow Awards: The Helmholtz
Association conferred the awards,
which are endowed with 20 000
euros each, to Prof. Dr. Harald von
Boehmer, Harvard Medical School in
Boston, and Prof. Dr. Naftali Kaminski,
University of Pittsburgh.
With top marks to POF III: International
reviewers convince themselves of the
quality and strategic relevance of the
new research program Genes and Environment in Common Diseases within
the framework of the program-oriented
funding of the Helmholtz Association.
JANUARY 14th
FEBRUARY 25th
Personalized assessment of the
long-term effects of medical radiation
exposure: Dr. Peter Jacob coordinates
the research program ‘PASSOS’,
which is financed by the Federal
Ministry of Education and Research
with around three million euros.
Walther and Christine Richtzenhain
Prize for Prof. Dr. Mathias Heikenwälder: The junior research group
leader at the Institute of Virology
receives the 10 000 euro prize for
clinical applications in oncology.
MARCH 16th
Funding notifications received:
Helmholtz Zentrum München, Leibniz
Institute of Plant Genetics and Crop
Plant Research (IPK) Gatersleben and
Forschungszentrum Jülich participate
in the German Plant Phenotyping
Network (DPPN) of the Federal Ministry of Education and Research.
MARCH 25th
APRIL 4th
One hundred mark passed: The
Center participates in more than 100
projects within the Seventh Research
Framework Programme of the European Union, acquiring more than 50
million euros in third-party funding
for this purpose.
APRIL 6th
MAY 1st
Leading virologists in Munich: Upon
invitation of the Institute of Virology
of Helmholtz Zentrum München and
Technische Universität München, the
Global Virus Network discusses new
insights concerning the fight against
virus-associated infectious diseases.
Institute of Computational Biology is
established: Prof. Dr. Dr. Fabian Theis
becomes director of the new institute
at Helmholtz Zentrum München and
also assumes the Chair of Mathematical Models of Biological Systems at
MAY 1st
Management expanded: Dr. Alfons
Enhsen takes up his duties as managing director for the scientific-technical infrastructure at Helmholtz
Zentrum München.
MAY 5th
Environmental biologist in the Top
50: Prof. Dr. Michael Schloter, head of
the Research Unit of Environmental
Genomics, is 22nd in the Laborjournal
ranking of the most cited researchers
in the field of microbiology.
MAY 9th
Federal Minister Prof. Dr. Johanna
Wanka confers Leibniz Prizes: Prof. Dr.
Vasilis Ntziachristos, director of the
Institute of Biological and Medical Imaging at Helmholtz Zentrum München
and professor of Biological Imaging
at Technische Universität München is
recipient of one of the prizes endowed
with 2.5 million euros each of the
German Research Foundatiion.
MARCH 20th
Improvement of tumor radiotherapy:
Prof. Dr. Gabriele Multhoff and Dr.
Daniela Schilling of the Clinical Cooperation Group “Innate Immunity in
Tumor Biology” receive a grant of the
Wilhelm Sander Foundation endowed
with 190 000 euros for the development of new treatment approaches.
China Scholarship Award for biologist
of the Center: Dr. Jin Zhao of the Institute of Biochemical Plant Pathology is
among the 31 German prizewinners
of the Chinese Government Award for
Outstanding Self-financed Students
Abroad.
APRIL 10th
Plant researcher in the Top 50: Dr.
Klaus Mayer, head of the Research
Unit of Genome and Systems Biology
of Plants, ranks fourth among the
most cited scientists in his field in the
Laborjournal ranking.
MAY 30th
JUNE 1st
Two new junior research groups at
the Center: Dr. Jantje Mareike Gerdes
heads the newly founded junior
research group “Primary Cilia and
Energy Metabolism” at the Institute of
Diabetes and Regeneration Research.
At the same time, the research group
“Mechanisms of Gene Regulation in
T cells" led by Dr. Elke Glasmacher
begins work at the Institute for
Diabetes and Obesity.
JUNE 4th
Research supports environmental
policy: Prof. Dr. Annette Peters, director of the Institute of Epidemiology II,
presents the current status of knowledge on the impact of air pollution on
health at the Green Week Conference
2013 in Brussels.
JUNE 21st
TransAqua is launched: Four institutes of Helmholtz Zentrum München
participate in the joint project for the
transfer of radionuclides in aquatic
ecosystems, which is funded by the
Federal Ministry of Education and
Research with four million euros.
JULY 1st
ESPGHAN Award 2013 for Dr. Eva
Reischl: The deputy head of the
research group “Complex Diseases”
of the Research Unit of Molecular
Epidemiology receives the award of
the European Society for Paediatric
Gastroentology, Hepatology and
Nutrition, which is endowed with
30 000 euros.
MAY 23rd
Prof. Dr. Bernhard Michalke confirmed
as FESTEM president: The head of
the platform “Central Inorganic
Analysis” at Helmholtz Zentrum
München is elected for the third time
as President of the Federation of
European Societies on Trace
Elements and Minerals (FESTEM).
m4 Award goes to Dr. Bernhard Frankenberger: For a specific immunetherapy against autoimmune diseases
and leukemia, the team led by Dr.
Bernhard Frankenberger and Prof.
Dr. Dolores Schendel at the Institute
of Molecular Immunology receives
the award of the Bavarian Ministry of
Economic Affairs, which is endowed
with 500 000 euros.
T IMELINE 2013
T IMELINE 2013
14 15 Timeline 2013
JULY 1st
Launch of the National Cohort: Prof.
Dr. Johanna Wanka, Federal Minister
of Education and Research, presents
in Berlin the largest German health
study with 200 000 participants.
Helmholtz Zentrum München is
building the new central biorepository on the Neuherberg campus for the
National Cohort.
JULY 3rd
Health economists to meet in Munich:
Prof. Dr. Reiner Leidl, Institute of Health
Economics and Health Care Management, becomes designated chairman
of the German Society for Health Economics and organizer of the 6th Annual
Meeting of the Society in March 2014 at
Ludwig-Maximilians-Universität.
JULY 4th
Decision-making structures profiled:
The Supervisory Board of Helmholtz
Zentrum München adopts the revised
version of the Partnership Agreement
and the Rules of Procedure of the
Management Board.
JULY 19th
OCTOBER 10th
NOVEMBER 29th
Pin of Honor for Georg Gerl: The
manager of the Scheyern Experimental Farm in the research
alliance Agroecosystems Munich
receives the blue Pin of Honor of
The Wilhelm Sander Foundation
supports therapy approach for lung
tumors: Prof. Dr. Reinhard Zeidler,
Research Unit of Gene Vectors, receives 120 000 euros for his research
project.
JULY 31st
OCTOBER 15th
The Eva and Klaus Grohe Prize goes
to Dr. Michael Schindler: For his
research in the field of infectious
diseases, the scientist of the Institute
of Virology receives the prize of the
Berlin-Brandenburg Academy of
Sciences, which is endowed with
20 000 euros.
Summer campus 2013 begins: 50 children of staff participate in two-week
holiday research program for kids.
AUGUST 1st
Official personal dosimeter service
under new management: The physicist
Markus Figel takes over the management of Germany’s number one
personal dosimeter service, which is
located at Helmholtz
Zentrum München.
AUGUST 5th
Dissolving protein complexes on
the atomic level: At the Institute of
Structural Biology under the direction
of Dr. Dierk Niessing, a new X-ray
crystallography platform is available
for drug development.
AUGUST 7th
SEPTEMBER 2nd
Career start: Accompanied by mentors
of the second year of training, 23
young people begin their apprenticeships in one of eight vocational training programs at Helmholtz Zentrum
München.
SEPTEMBER 10th
ERC Advanced Grant for Prof. Dr.
Magdalena Götz: The European
Research Council (ERC) supports
the research of the director of the
Institute of Stem Cell Research and
chair of Physiological Genomics at
Ludwig-Maximilians-Universität with
a grant amounting to 2.38 million
euros over five years.
SEPTEMBER 16th
New member of Leopoldina: Prof.
Dr. Matthias Tschöp, director of the
Institute for Diabetes and Obesity, is
accepted into the National Academy
of Sciences.
JULY 10th
SEPTEMBER 19th
State Prize for two office administrators: Paulina Zangler and Christine
Zimmermann are honored for
outstanding achievement during their
vocational training with the Bavarian
State Prize.
Colloquium for Prof. Dr. Rupert
Lasser: With a two-day farewell
conference, the Institute of Biomathematics and Biometry says goodbye to
its founding director.
JULY 16th
Ilse Aigner visits Scheyern: In her
capacity as Federal Minister for
Nutrition, Agriculture and Consumer
Protection, the Bavarian politician
informs herself at the Experimental Farm of the Center regarding
research on the ecological impacts of
climate change.
SEPTEMBER 20th
Science Prize of the city of Freising for
Dr. Nilima Prakash: The scientist at the
Institute of Developmental Genetics,
together with Prof. Dr. Antonio
Simeone, University of Naples, Italy,
receives the Science Prize endowed
with 20 000 euros for their joint
research on Parkinson's disease.
Networking with the world’s top
scientists: To kick off the HelmholtzNature Medicine Diabetes Conference
of Helmholtz Zentrum München and
the journal Nature Medicine, Prof. Dr.
Matthias Tschöp presents the Lifetime
Award to Harvard researcher Prof. Dr.
C. Ronald Kahn.
Increased funding for the promotion of young scientists: The junior
research group “Molecular Endocrinology”, led by Dr. Nina Uhlenhaut,
begins work at the Institute for
Diabetes and Obesity.
SEPTEMBER 25th
German-Chinese cooperation agreement signed: The Institute of Virology
at the Bejing Institute of Genomics
cooperates in the investigation of the
interactions of the hepatitis B virus
with its host.
Best in Big Data: Clueda AG, a spinoff of Helmholtz Zentrum München,
wins the competition of the journal
Computerwoche against 18 competitors with a computerized analysis
system for stock traders.
SEPTEMBER 27th
Milestone for process organization:
Dr. Nikolaus Blum, CFO, and Dr. Uwe
Bott, head of Human Resources
Development, inform the staff
about the experience and success
in implementing a process-oriented
organization.
OCTOBER 1st
Oktoberfest Symposium 2013: In
cooperation with the German Center for
Diabetes Research (DZD), Technische
Universität München and the Competence Network Diabetes Mellitus, the
Institute of Diabetes Research is inviting
participants to a seventh symposium.
OCTOBER 17th
NOVEMBER 16th
Knowledge for all: During the 13th
Munich Science Days the Center
informs the numerous visitors to the
Theresienhöhe about diabetes.
NOVEMBER 25th
Award for new approach to treat
leukemia: Seven scientists receive the
Research Award for Interdisciplinary
Cooperation of the Association
of Friends and Sponsors (VdFF) of
NOVEMBER 29th
OCTOBER 3rd
Insights of lung research: The third
Munich Lung Conference begins in
the Comprehensive Pneumology
Center with contributions by international experts.
AUGUST 27th
Clinical Research Award for Prof. Dr.
Anette-Gabriele Ziegler: The director
of the Institute of Diabetes Research
receives the Mary Tyler Moore and
S. Robert Levine Excellence in Clinical
Research Award of the Juvenile
Diabetes Research Foundation for her
research into new therapies and preventive measures for type 1 diabetes.
SEPTEMBER 22nd
Helmholtz dissertation prizewinner
in the research field of Health: Dr. Jan
Krumsiek, Institute of Computational
Biology, is one of the winners of the
Helmholtz Doctoral Award, which
was conferred for the first time.
Further expansion of international
cooperation: Managing Director Dr.
Alfons Enhsen welcomes the Chinese
science delegation of the Chinese
Academy of Sciences during its information visit to Helmholtz Zentrum
München.
DECEMBER 3rd
Winner of the Ernst Schering Prize
2014 is announced: Professor Dr.
Magdalena Götz, director of the
Institute of Stem Cell Research at
Helmholtz Zentrum München and
chair of Physiological Genomics at
Ludwig-Maximilians-Universität
München, receives the prize, which
is endowed with 50 000 euros, for
her research on the molecular basis
of brain development.
INT ERVIEWS WIT H T HE MANAGING DIRECTORS
16 17 Our Concepts and Results
Are Convincing
2. As a vice president, you are responsible for
the Research Field Health within the Helmholtz
Association. How well is our center anchored
thematically in the Helmholtz Association?
Wess: The Center’s profile correlates well with the
mission of the Helmholtz Association. Our research
activities range from basic research to translational
research. Our research topics address the major
challenges of the future.
3. Health research at Helmholtz Zentrum
München shall ultimately benefit patients. How
can we strengthen our translational approach in
order to translate research results into medical
applications?
Wess: To limit translational research only to translational medicine would be too short-sighted.
Of course, as a scientific-technical center we
are interested in good collaborations and joint
projects with university hospitals because we do
not want to have own wards with beds. However,
we are keen that our research results benefit
patients, as our three translational centers show.
But translation involves much more: It includes
early-stage drug discovery projects, the search
for new biomarkers or even technical equipment
for imaging. Another aspect relates to spin-offs.
Here, with 18 spin-offs that have generated several
hundred jobs, we are the most successful center in
the Helmholtz Association. And finally, we always
forget that translation also includes knowledge
transfer to society, which can hardly be expressed
in the usual statistics. This includes insights into
new or improved treatment regimens, as well as
findings from environmental research.
Prof. Dr. Günther Wess, CEO,
Helmholtz Zentrum München, is at
the same time vice president and
coordinator of the Research Field
Health in the Helmholtz Association. In the interview, Günther
Wess describes the successes and
strategic developments as well as
the major challenges the Center
will face in the next few years.
1. Helmholtz Zentrum München achieved outstanding evaluation results in the expert review
within the framework of program-oriented
funding. What makes us the leading center in
the field of environmental health?
Wess: In 2008, under the motto “One 2013”, we
aimed to become a leading international center in
the field of environmental health within five years.
The steadily increasing number of high-caliber
publications and the comments of many international
reviewers, most recently during the POF III review,
demonstrate that this aim has been achieved. We
received an excellent assessment in the POF III
review. What impressed the reviewers besides the
top achievements of individual scientists was the
interaction between various disciplines under
one common topic. Furthermore, we have a good
balance between our focus on certain common
diseases and technology platforms combined with
our expertise in health research and environmental
research. With a total of 12 ERC grants, we are the
most successful center in the Helmholtz Association.
4. How are we expanding our endeavors
to promote young scientists, now after the
successful positioning of the HELENA graduate
school?
Wess: One of our great strengths is the promotion
of young scientists. Our HELENA graduate school
is internationally established with about 330 PhD
students, and it has become a brand name among
graduate schools. A post-doctoral program has
just started, for which there is great demand
internationally. And first pilot projects for a
combined MD-PhD program are in the planning
stage that shall give physicians the opportunity
to conduct scientific research.
A brand new project entitled Pioneer Campus is
also being planned. With this program, we want
to attract young international “star scientists” to
Munich, where they can carry out interdisciplinary
research projects under ideal conditions, also with
great potential for technical-medical applications.
This might be a bridge between the disciplines
of engineering and biology, i.e. "bioengineering".
5. Successful research requires motivated
researchers. What do we need to offer our
scientists to tie them to the Center?
Wess: I see major challenges in the area of
mid-level scientists. Here at the Center there is a
group of about 200 people, some in management
positions and with fixed-term contracts. These
are important staff members, without whom our
center would not function. It will be crucial to
develop new concepts for our personnel and also
to find new forms of remuneration, which take
performance and function into greater account.
A solution is still not in the offing, but the topic
must be addressed and receive more attention.
6. What is the greatest challenge facing our
center in the next few years?
Wess: Our greatest challenge is the renovation
of the infrastructure and its further development. Decades of missed opportunities are now
apparent. A few years ago we began a renovation
program, using funds of the Center and federal
funds from the economic stimulus program, but
this was just a drop in the ocean. New laboratory
space was leased where we could launch our new
activities, and the new diabetes building supported
by Bavaria’s Minister President Seehofer helps a
lot. But that is not enough to remain internationally competitive. Additional resources are urgently
needed.
7. The Center hosts international conferences
and events more and more often. What is the
objective?
Wess: We follow the recommendations of our
Scientific Advisory Board to increase our international visibility through high-level symposia and
conferences. Thus, in 2013, the first HelmholtzNature Medicine Diabetes Conference took place
with the Helmholtz Diabetes Lecture by Ronald C.
Kahn and the presentation of the Helmholtz Young
Investigators Diabetes Award. Similarly, the already
well-established “Oktoberfest Symposium” and the
international Munich Lung Conference were held.
This year the Center is participating in the Conference of the European Respiratory Society with more
than 20 000 attendees, which will also take place
in Munich. Unfortunately, we could not in the past
and cannot presently host these important events
on the Neuherberg campus due to lack of space and
infrastructure.
18 19 8. Cooperation is central to successful research.
How shall we develop our cooperation networks
further, also against the backdrop of new
forms of cooperation between university and
non-university research?
Wess: Technische Universität and LudwigMaximilians-Universität are our most important
cooperation partners in Munich, and many joint
appointments form the backbone of our common
endeavors. In the framework of the German Centres for Health Research and a global orientation
of the Helmholtz Association and our center, we
have also undertaken joint appointments with
other locations. With the Karlsruhe Institute of
Technology (KIT), and the recently founded Berlin
Institute of Health (BIH), interesting new models
of collaboration between university and non-university research have emerged. With the BIH, the
Federal Government has undertaken a strategic
step using considerable resources to strengthen
the research location of Berlin. At the present time,
the question cannot be answered whether such
models are also possible and useful in Munich.
Sonja Opitz, head of Corporate
Communications, spoke with Prof.
Dr. Günther Wess.
9. We have focused our research on the major
common diseases. What shall we focus on in
the future?
Wess: In recent years, the Research Field Health
has very successfully focused on widespread,
common diseases. The founding of the German
Centres for Health Research has provided
additional impetus. In the framework of this
strategic orientation, we are ideally positioned
with our center motto “Health and Environment”.
It is immediately clear that lung diseases play a
prominent role among the environment-related
diseases. However, it is also increasingly evident
that environmental factors such as diet, lack of
physical activity, stress and personal lifestyle
play a very important role in diseases such as
diabetes. That is why research on these diseases
fits perfectly in the Center profile. We were very
pleased about the suggestion from the experts of
the POF III review to strengthen our activities in
the allergy field. We will be glad to take up this
suggestion and would like to develop allergy as
the third pillar of the Center alongside diabetes
and lung diseases. Here the Center is in a unique
position because the environmental field can
make significant contributions due to its research
in the topic of pollen, analysis or microbiome
research in the future. And finally, we should not
neglect to mention that we play an important role
in the field of virus research in the German Center
for Infection Research.
BRIEF PROFILE
DR. MARTINA HANSEN
As head of Program Planning
and Management, Dr. Martina
Hansen supports the Board of
Directors in the strategic development and implementation
of the scientific programs. Her
department is the link between
management and research; it
conducts the scientific con-trolling and provides support in
the acquisition of third-party
projects. Science education and
training and the promotion of
young scientists are also part
of the department’s responsibilities.
10. As part of the POF reviews, we received
recommendations. How shall we implement
these?
Wess: The POF program was created in science
with great support of Program Planning and Management. It must also be implemented in science.
Only when it is accepted by the broad basis of
scientists it can be successfully implemented with
appropriate administrative support. To achieve
this, the Board of Directors has developed a strategic plan in coordination with the topic speakers
on the basis of recommendations of the Helmholtz
Senate. It was discussed and endorsed by the
Scientific Advisory Board. This strategic plan was
then adopted by the Supervisory Board. In the
coming months it will be important to work out the
detailed implementation in the topics on a broad
basis in science, with the support of Program
Planning and Management. It will be important to
develop many good ideas to enhance our leading
position internationally.
The new governance will help us to achieve this.
The Management Committee has a stronger participation of scientists than was formerly the case.
Through the participation of the program speaker
as well as the topic speakers and the respective scientific coordinators, we can discuss scientific issues
much more intensively and then make our decisions.
20 21 Modern Administration
is a Team Sport
2. Science and administration often feel as if
they belong to two different worlds. How can
this gap be bridged?
Blum: Administration and science are indeed two
different worlds. Science is judged on academic
performance criteria such as the journal impact
factor and the acquisition of external funding.
From the administrative side, however, the
funding entities expect that the proper execution
of administrative processes is ensured. Our task
is to bring these two worlds together and thus to
create an effective Center. A new approach is the
establishment of the Department of Operations
and Support, abbreviated OS. With this we wanted
to combine the requirements of science and administration as constructively as possible.
3. How must we imagine this?
Blum: Operations and Support has both an interpreter and a support role. It should translate the
needs of science into administrative action and
at the same time coordinate this action for the
purposes of the scientific projects. OS teams are
made up of staff members from science and from
the administration. A prime example showing the
enormous added value of support through OS is
when institutes are founded. New institute directors
or junior research group leaders must first spend a
lot of energy learning how to process procurements,
what the hiring procedures are and what possibilities exist for cooperation. With OS, they have a
designated contact person who is familiar with the
processes and knows how to cope with them.
Dr. Nikolaus Blum, CFO of the
Center, served as vice president
of the Helmholtz Association until
the end of 2012. In that capacity he
advocated more flexibility and a
de-bureaucratization of scientific
structures. In the interview Dr.
Blum explains his ideas on the role
and development of administrative
organizational forms at Helmholtz
Zentrum München.
1. Dr. Blum, science at the Center has developed
further and at the same time the complexity of
the research landscape has increased overall.
What challenges for the administration arise
from this fact?
Blum: A major challenge has been the immense
growth of the Center. In the last five years the
number of employees, the number of procurements and financial transactions have increased
by around 50 percent. With the German Centres
for Health Research, the National Cohort and the
Initiative and Networking Fund, new financing
models for science have emerged. This has led to
a high complexity of the current research structures. The administration has had to cope with
the growth process of the Center and at the same
time has had to deal with this complexity.
4. What changes can we expect with the introduction of process-oriented organization?
Blum: Process-oriented organization shall serve
to efficiently process the greatly increased number of standard operations. Each year, we hire
approximately 800 employees and process 45 000
procurements. With process-oriented organization, we create the conditions to handle these
operations quickly and smoothly with all participating administrative units. This change should
not be underestimated!! It is a great challenge,
because it requires teamwork and the ability to
think “outside the box” from all involved. Modern
administration is a team sport.
5. In addition to the introduction of OS and
process-oriented organization, the administration is continuing to develop its services for
science. What concrete measures do you have
on your agenda?
Blum: Our catalog of measures is derived consistently from the annual goal for 2014, ranging
from improved information and communication to
financial processes and personnel matters. Regarding
personnel, a policy for fixed-term contracts shall be
adopted and implemented this year: Employees with
fixed-term contracts shall thus gain more planning
security. An applicant management system will be
introduced to give the Human Resources Department stronger support in dealing with applicants
– that is also a very important point for the public
image of the Center. And finally, we will provide the
institutes and research units with regular budget
information, so that researchers can navigate their
resources more easily and efficiently.
6. Since the beginning of 2014 the new
governance has been in operation at the Center.
To what extent will our core business –
research – profit from these new structures?
Blum: The new partnership agreement and the
new governance relate primarily to the external
management of the Center, i.e. the interaction of
shareholders, the Supervisory Board and the Board
of Directors. The Public Corporate Governance
Codex now also applies to the Center. Despite
all the changes, we will continue to intensively
implement the internal coordination processes. In
the Center, the changed governance will result in
noticeably increased action and responsiveness.
Research will benefit from faster decision making.
Today speed is an absolute competitive advantage
also in science.
22 23 7. With compliance management, a new internal structure has been created at the Center.
What role will it play?
Blum: Compliance means that an organization
complies with existing laws and regulations. That
is something that is taken for granted. The public
and the funding entities expect this from Helmholtz
Zentrum München. However, the spectrum of laws
and regulations to be observed today is very broad
and ranges from legal matters, the annual financial
statements, the use of research funds, work safety
and IT security to Good Scientific Practice. Compliance management ensures that the framework
conditions are known and observed. There are
indications of possible vulnerabilities. Compliance
management is therefore an aid for all managers,
who must ensure that the existing regulations are
observed in their area of responsibility.
8. How can we position ourselves optimally in
the international competition to attract the best
researchers?
Blum: The attractiveness of the Center for foreign
scientists arises primarily from our scientific
performance. If this is outstanding, many scientists
from other countries will want to come to our
center. But of course we must offer the international
scientists good conditions and support them in
their integration. Here the administration can make
an important contribution, by providing contact
persons and assistance in finding housing, the
appropriate schools or childcare. In the long term
we will also raise the issue of personnel marketing
to the international level. Against the background
of demographic change in Germany, we are
dependent on the recruitment of highly qualified
foreign employees.
Sonja Opitz and Cordula Klemm (from
right), Corporate Communications,
spoke with Dr. Nikolaus Blum.
BRIEF PROFILE
DR. STEFAN ECHINGER
9. We recruit talent from the outside – how
can we promote the potential of staff members
at the Center?
Blum: Talent management is one of our most
important issues. As a research institution,
our primary role is to promote and train young
scientists. There are proven instruments for this,
such as the Graduate School HELENA or research
groups with a tenure track option. But of course
the Center must have excellent employees in all
its positions. Therefore, our talent management
is very broad. Our internal qualification program
has grown tremendously in recent years and
supports the development of the Center with a
number of targeted measures. The offers of the
Munich Leadership Program, which we organize
for young professionals together with the Centre
for Science Management Speyer, and the offers of
the Helmholtz Academy are open to employees.
Human Resources Development at the Center
ensures that the strategic objectives for promoting
talent remain in focus.
10. You successfully advocated more flexible conditions in the recruitment of scientific
personnel in the Helmholtz Association. How
can we use this new freedom provided by the
Academic Freedom Act in the best possible way?
Blum: The Academic Freedom Act has different
aims. It affects financial leeway, personnel
questions, construction matters and participation
options. One of the new possibilities is to carry
out construction projects up to a volume of five
million euros in each center’s own responsibility,
if a corresponding construction controlling exists.
We are currently planning to take advantage of
this opportunity. We are also planning further
measures with regard to personnel.
Dr. Stefan Echinger is head of
Operations and Support. His
team supports the Board of
Directors in the development
of scientific organizational
units. Operations and Support
is responsible for the implementation of new units on
an administrative level and
coordinates the decentralized
management of the center
location Grosshadern.
11. For years Helmholtz Zentrum München has
been committed to improving equal opportunities for women scientists. Has the end of the
flagpole been reached?
Blum: Increasing the percentage of women,
also and especially in leadership positions, is a
declared goal of Helmholtz Zentrum München. A
look at the numbers reveals that we have made
good progress. We pay great attention to the
equal treatment of men and women and use a
variety of funding instruments in order to increase the proportion of women in management
positions. However, there is certainly potential
for more creative measures. In our view, improving the compatibility of work and family plays
a key role. The campus kindergarten is already
functioning very well. Through the Academic
Freedom Act, the Center now has the opportunity
to develop further offers of support from its own
income. We hope that we can make an additional
interesting offer for young families still this year.
12. What contribution can highly qualified
science management make for the international
positioning of German health research and
in particular research at Helmholtz Zentrum
München?
Blum: In today's complex structures, science is
not possible without good science management.
It is an essential success factor for modern,
interdisciplinary research. Of course, science
management has a supporting role and will never
replace the originality and creativity of outstanding
scientists. However, in national and international
competition, the successful implementation of
projects, cooperation in networks and in particular, the provision of facilities with the necessary
equipment and consumables are no longer possible
without qualified research management.
24 25 Making the Campus
Ready for the Future
renovating. These must be decommissioned and
deconstructed in order to create new areas for
construction. We will retain the core of buildings
that can be renovated and expand them for
sustainable use. New construction will take place
according to modern concepts. Based on the
existing buildings, the contamination situation,
energy-technical considerations and the usability
of the building structure, we must develop the
campus so that we can react flexibly to future
demands for use.
3. Our center is extensively expanding its diabetes research. Two new diabetes institutes and a
new research unit are being established – where
will the employees/staff members and laboratories be accommodated?
Enhsen: The new Helmholtz Diabetes Campus
is in the planning stage. It will encompass two
laboratory-office complexes for more than 200
employees respectively and another building on
the Helmholtz Pioneer Campus for more than
150 employees. Over the short term we need to
lease office and lab space outside of the campus.
We have already set up two new diabetes
institutes in Garching and the Comprehensive
Pneumology Center in Grosshadern.
Dr. Alfons Enhsen is Managing
Director for the Scientific-Technical
Infrastructure. In the interview he
offers an outlook on the intended
development of the campus and
explains his ideas and wishes for
the future expansion of the Center.
1. Dr. Enhsen, your primary objective in your
new position is to make the campus fit for the
future. What project is at the top of your agenda?
Enhsen: My objective is to develop and implement a long-term perspective for the Neuherberg
campus. This includes the long-term development
of the master plan and parallel to this, the shortterm creation and provision of work space, in
particular laboratory space.
2. What is your highest priority for the development of the master plan?
Enhsen: We need to develop the campus so that
it is flexible and optimally used – now and for
future generations of researchers. This means:
identification of contaminated sites, renovation,
new construction. A number of the buildings and
part of the infrastructure date from the late sixties
and seventies. Some buildings are no longer worth
4. The Helmholtz Pioneer Campus shall provide
exceptional young scientists with maximum
opportunities for creative research. How will
this be reflected in the architecture?
Enhsen: In the Helmholtz Pioneer Campus, abbreviated HPC, several scientific disciplines shall
work together under one roof. The horizontal
and vertical circulation of the building fosters the
interaction between the different disciplines and
scientists. The HPC will be directly connected to
the two new diabetes buildings. Thus, the already
existing institutes will have direct contact to the
young scientists in the HPC. The architecture
will be open and communicative. The young HPC
scientists will conduct their research in flexible,
large laboratories equipped with state-of-the-art
technology.
5. Research thrives on the direct exchange
between scientists. What opportunities does
our campus, which is close to the Munich city
limits, offer for the creation of communicative
meeting places?
Enhsen: An attractive campus needs facilities for
an open exchange at all levels in order to ensure
that its central mandate – the transfer of knowledge – is carried out. There is a great need for
appropriate space in the Center. In all major
remodeling projects and new construction projects,
we of course take into consideration the aspects
of communication and interaction. The aim is
to promote the exchange of ideas and cooperation between the teams. Traffic connections to
the Center also play an important role. Good
accessibility by public transportation increases the
attractiveness of the Center enormously, especially
for young scientists and students. In a pilot project
with the Munich Public Transport Company, we
were able to improve the connections. In the future,
however, we want to optimize this further.
6. The Center wants to expand the field of stem
cell research. What stands in the way of rapid
implementation?
Enhsen: Stem cell research at Helmholtz Zentrum
München will be located in the future in what
is now the Hämatologikum in Grosshadern. The
building needs major renovation in various
ways, and it will be completely modernized in
the coming years during ongoing scientific
operations. Unfortunately, we don’t have any
alternative space, neither for laboratories nor for
infrastructure facilities, so we can’t vacate the
building completely during renovation. We therefore have to convert and modernize the building
floor by floor.
7. The Center competes for the best talent
worldwide. How important are state-of-the-art
infrastructure and high-end technology in this
competitive situation?
Enhsen: To be internationally competitive and to
achieve top results, both the scientific environment
and the working environment with the buildings,
the infrastructure and how well the facilities are
equipped with modern technology are essential.
The campus is optimally positioned in the science
region of Munich. Our task is to modernize the
campus and design the working environment in an
optimal way to ensure efficiency.
26 27 8. From whom can we learn here?
Enhsen: As a rule from the best in the class. We
belong to the best in science, but not in infrastructure. Science is developing so fast that the
infrastructure can’t keep pace. This problem can
be met to some extent by abandoning the use
of small-scale lab and office units and instead
creating large, flexibly usable work space. But
it would be particularly important that we work
on the overall project duration and reduce this
considerably. At the moment we are trapped in
a situation in which we need eight to nine years
for a new construction project. The private sector
manages to complete a project of the same size
and complexity in just two to two and a half
years. Of course, projects in the private sector
and the public sector cannot be compared one
to one. The federal and state governments must
be allowed to carry out the test and control
mechanisms with the corresponding approval
times, since they are working with tax money. But
an ambitious goal would at least be to reduce the
current project duration times by half and thus
to strive for a considerable reduction of the
financial risk. That would definitely be a success.
Cordula Klemm and Sonja Opitz (from
left), Corporate Communications,
spoke with Dr. Alfons Enhsen.
9. What role do occupational safety and fire
protection play for you?
Enhsen: Occupational safety affects the health of
each individual employee as well as his or her colleagues. Nothing should be given higher value. That
is why occupational safety measures, including fire
protection, are non-negotiable. This is a special task
at the Center, since we have a lot of staff turnover
among young scientists, PhD students and postdocs.
Every year there are 500 to 600 new employees at
the Center, who all must be trained in occupational
safety and introduced to the work environment. The
responsibility for this lies with the institute directors. Our task is to support the institute directors
and staff members who have a supervisory role in
this endeavor with our expertise. We need to ensure
that all employees are familiar with all safety regulations, taking into account that people with many
different nationalities and native languages work
here. Through annual training modules and regular
information, we keep the staff aware of the topic.
Fortunately, in addition to the Department of Infrastructure and Safety (ISA) which covers all safety
aspects, we have many volunteer safety officers in
the institutes. We also have many volunteers in the
fire department and hope that in the future staff
members will support this important task.
BRIEF PROFILE
DR. DRAZENKA SELESI
As coordinator, Dr. Drazenka
Selesi supports the establishment and development of
the scientific and technical
infrastructure. She works in
a team with the Department
of Scientific Infrastructure,
Technical Safety and Occupational Protection headed by Dr.
Alfons Enhsen and the Central
Technical Facilities.
10.You have been managing director for the scientific-technical infrastructure in the Center since May 2013. What has
impressed you the most?
Enhsen: What impresses me is the science. The progress made
here at the Center in recent years seeks its comparison in
Germany. Science at the Center plays in the top league. That’s
why I very much wish to contribute to the development of the
infrastructure, in order to meet the expectations placed in us
and to achieve our ambitious goals for the future.
Commitment to Promote
the Advancement of
Young Scientists
Helmholtz Zentrum München sets standards in the promotion of young
scientists. The Helmholtz Graduate School Environmental Health (HELENA)
is unique in Europe and is qualifying a new generation of internationally
competitive doctoral students. A newly developed postdoctoral fellowship
program complements the strategic concept of promoting young talent.
The opportunity to be a leader of well-equipped junior research groups
offers young scientists from around the world an ideal career springboard.
The Helmholtz Graduate School Environmental
Health (HELENA), which was founded in collab
oration with Munich’s two elite universities,
is internationally recognized as a successful
model. It offers doctoral students at Helmholtz
Zentrum München an interdisciplinary graduate
program within eight thematic fields, which
can be tailored to fit each student’s specific
interests and needs.
The research focus is on the interaction of
individual genetic predisposition, environmental
factors and lifestyle and their influence on
the pathogenesis of major common diseases.
The interdisciplinary training and fostering of
social skills and leadership skills shall prepare
the doctoral students to assume leadership
positions in science and industry. With the
Research School Lung Biology and Disease and
the Research School of Radiation Sciences,
the Helmholtz Association supports its own
research school respectively in the fields of
lung biology and radiation research under the
umbrella of HELENA.
At the end of 2013, in the third year of its
existence, the graduate school HELENA had 328
members. The doctoral students belong to 48
different nationalities. Besides Germany and
European countries, particularly China is strongly
represented.
The postdoctoral fellowship program at Helmholtz Zentrum München was launched in late
2013 with an international call for applicants.
Each year, the program recruits ten highly qualified postdocs for three years in full scientific
staff positions in the designated thematic fields
of the Center. The postdoctoral fellows receive
individual mentoring as well as coaching when
applying for external funding. The participants
in the program are fully integrated into the
research environment of their respective institute and are prepared for a successful career in
academia or industry.
With its junior research group program,
Helmholtz Zentrum München was able to
recruit young top researchers from around
the world. At the end of 2012 the Center had
14 junior research groups; by the end of 2013
this number had risen to 19. Thirteen of the
19 junior research groups are led by women
scientists; seven were funded through Starting
Grants of the European Research Council.
BASIC TRAINING
Biology and
Diseases of
the Lung
Diabetes
and Metabolic
Diseases
Radiation
Research
Neuro and Stem
Cell Biology
GRADUATE SCHOOL
HELENA
Infection, Immune
and Tumor
Biology
LE
Systems Biology,
Imaging and
Structural Biology
Epidemiology,
Health Economics
and Human
Genetics
AD
ER
SH
I P,
MAN
Ecosystems
Biology
M
AGEMENT AND CO
M
I
UN
CA
O
TI
N
Countries
of Origin of
HELENA
Doctoral Students
1.EGYPT
13.HAITI
25.CROATIA
37.SWEDEN
2.ALGERIA
14.INDIA
26.MALAYSIA
38.SERBIA
3.USA
15.IRAQ
27.MACEDONIA
39.SLOVENIA
4.BANGLADESH
16.IRAN
28.MEXICO
40.SPAIN
5.BOLIVIA
17.ISRAEL
29.NEW ZEALAND
41.SOUTH AFRICA
6.BRAZIL
18.ITALY
30.NETHERLANDS
42.TAIWAN
7. UNITED KINGDOM
19.JAPAN
31.AUSTRIA
43.CZECH REPUBLIC
8.CHINA
20.JORDAN
32.PHILIPPINES
44.TURKEY
9.GERMANY
21.CANADA
33.POLAND
45.UKRAINE
10.ECUADOR
22.KENYA
34.PORTUGAL
46.HUNGARY
11.FRANCE
23.COLOMBIA
35.ROMANIA
47.VENEZUELA
12.GREECE
24.KOREA
36.RUSSIA
48. VIETNAM
YOUNG SCIENT ISTS
YOUNG SCIENT ISTS
32 33 Three Years of HELENA
Jan Krumsiek‘s calendar is as full as that of a successful manager: In
January he spent a few weeks again at Weill Cornell Medical College
in New York to advance his scientific work. At the same time, he leads
his own research team at the Institute of Computational Biology at
Helmholtz Zentrum München, supervises four doctoral students and
does a lot of work at the computer. In addition, he travels to attend
conferences and give lectures. And all this just a year after completing
his PhD degree.
The 30-year-old bioinformatician is one of the top young scientists
that Helmholtz Zentrum München has promoted in the HELENA
Graduate School of Environmental Health. Founded in November
2010, the school is an investment in the future, both for the students
and for Helmholtz Zentrum München. “The graduate school provides
interdisciplinary education and training in the field of environmental
health and is an ideal springboard to a successful career,” said
Christian Langebartels, director of HELENA and research director for
the field of environmental and radiation research. The spokesperson
of the graduate school is Hans-Werner Mewes, director of the Institute
of Bioinformatics and Systems Biology.
Photo above: The Neuherberg Doctoral Student Café is an informal meeting place for HELENA members.
Dr. Jin Shao, Sabine Bartel, Dr. Monika Beer, Tao Xu and Nirav Florian Chhabra meet here to discuss
their work.
Photo below: Dr. Jan Krumsiek’s dissertation was supervised by Prof. Dr. Fabian Theis (left). The
dissertation on the modeling of metabolic networks received doctoral awards from the Center, from
the Helmholtz Association and Technische Universität München.
Dr. Monika Beer is head of
the young scientist development program and scientific
education and training at
The biologist is responsible for
the HELENA graduate school
and the establishment of a
new postdoc program at the
center.
Jan Krumsiek had already begun his doctoral work when HELENA
was founded. He became a member right from the beginning and,
according to him, benefited a lot from the HELENA program. In
addition to attending lectures in specialized areas, he took advantage
of the interdisciplinary courses in presentation training, time and
self-management and courses on the steps involved in the publication
process. Since HELENA is also an associate member of the graduate
school of Technische Universität München, he additionally had the
opportunity to take their courses. “I attended a course in project
management, which was extremely useful,” he said.
The Thesis Committee, an integral feature of HELENA, offered him
guidance for his dissertation and in general for his doctoral work.
It is an advisory body, consisting of the individual’s PhD supervisor,
another adviser from the Center and an external expert, which
motivated him and supported him in strategic questions. “Once a year
the doctoral student meets with the Committee and discusses the
progress of his/her dissertation,” he said. “That forces you to structure
your work and helps you stay focused.” In 2013 Krumsiek was awarded
the Helmholtz Doctoral Award in the research field Health.
Krumsiek’s doctoral project involved processing thousands of
metabolic data sets from a study of the KORA platform (Cooperative
Health Research in the Region of Augsburg), which is coordinated
at Helmholtz Zentrum München. The bioinformatician created
correlation analyses between the individual values and depicted them
graphically. The result was images of networks which – according to
Krumsiek – “actually correspond to biochemical truths. We verified
that. What interested me especially about my topic was that in my
research group we spanned the spectrum between biology, medicine, mathematics and informatics. From the depths of biology up to
programming – everything was included.” Interesting and unexpected
conclusions could be drawn from the data: “We were able to visually
show that men and women differ greatly in their metabolism of amino
acids and fats,” said Krumsiek. “Even differences between depressive
and non-depressive individuals or people with asthma and healthy
people could be determined.”
Photo left: Jörg Bartel, Michael
Laimighofer, Ferdinand Stückler
and Kieu Do (from left) work
on their doctorate in the team
“Systems Metabolomics” led by
Dr. Jan Krumsiek at the Institute
of Computational Biology.
Krumsiek has a three-year
postdoctoral fellowship of the
Helmholtz Association. At the
same time he is a visiting fellow
at Weill Cornell Medical College
in New York.
YOUNG SCIENT ISTS
YOUNG SCIENT ISTS
34 35 And the novel graphical representation enabled yet another application: It provided evidence of metabolic pathways that were not known
before. Through the visualization of the network, researchers are now
able to assign metabolites to specific chemical processes. On the one
hand, this is a contribution to basic research. At the same time, this
approach also provides insights for human medicine. The graphical
network may help to elucidate diseases through blood tests.
The concept of the Thesis Committee also ensures that the students
have mentors and get away from the formerly common individual
doctorate. Around 330 graduate students are now taking part in
the programs of HELENA, of which 35 percent came from abroad.
“We have participants from 48 countries,” Beer said. “China is the
most strongly represented, with 50 persons. It is also interesting
that more than half of the participants are women.”
“The success of Jan Krumsiek shows how important it is to provide
interdisciplinary education and training for the doctoral students
within the framework of HELENA,” said Monika Beer, head of
Development for Young Scientists in the Department of Program
Planning and Management. “They are no longer left to fend for
themselves; they can seek advice, plan their careers and network
with each other.”
The preparation for professional life is also an important part of
the HELENA program. “We invite experts to career seminars to
inform the doctoral students about what career options are available in the future,” said Monika Beer. Around 40 percent opt for
academic careers; the others go into industry or science management. “We also want to show the young people career paths that
are different from the classical paths.” Jan Krumsiek has already
decided: He intends to stay at Helmholtz Zentrum München, where
he has received a postdoctoral fellowship for three years.
Sabine Bartel is pursuing her
doctorate at the Comprehensive Pneumology Center with
a dissertation on signaling
pathways in the development
of asthma. She will finish her
doctorate in summer 2014, after a research stay at Children’s
National Medical Center in
Washington, DC, USA, where
she learned a new method to
isolate gene fragments. In 2010
she received her Master’s
degree in Molecular Biotechnology from Technische
Universität München.
Nirav Florian Chhabra studied
biotechnology at Manipal
University in Karnataka, India.
He received his Master’s
degree from the University of
Manchester in the UK. Via an
immunological research project
at the University of Regensburg, Chhabra subsequently
came to Munich. For his
dissertation at the Institute of
Experimental Genetics he is
investigating gene functions in
the pancreas, which play a role
in the pathogenesis of diabetes.
“Due to the integration into HELENA
and the graduate research school Lung
Biology I am linked in a network with
other doctoral students. I can participate in conferences in my field, have
intensive discussions with visiting
scientists at the Institute and thus
grow into an international research
environment.”
Sabine Bartel
“HELENA was the perfect environment
for my doctorate. Through the HELENA
graduate program I received a firm
basis for my research career, in particular, how to write a good scientific
paper.”
Dr. Jin Zhao
“The Center conducts research on important topics and provides an excellent scientific infrastructure. I find the
education and training and scientific
supervision in the Helmholtz Graduate
School Environmental Health to be
very enriching. For my scientific work,
the KORA studies platform with its
well-studied cohorts is particularly
relevant. If possible, I would like to
remain for some time in Germany
after receiving my PhD degree.”
Tao Xu
“It was a good idea to come to Helmholtz Zentrum München. Here I have
an inspiring scientific environment. I
participate in the doctoral students’
initiative DINI, and as HELENA representative, I am committed to helping
build up the graduate school. And of
course, I want to support foreign students upon their arrival in Germany
with my experience.”
Nirav Florian Chhabra
“HELENA promotes doctoral students not only academically, but also
personally in terms of networking,
personal development and career
planning. I think that’s something
special.”
Christina Dargel
Dr. Jin Zhao received her doctor
ate with a dissertation on the
topic of the role of aquaporins
during lateral root formation
in plants. The results of her
research were published in
Nature Cell Biology (see page
98). Since 2013 she is a postdoc
in the Institute of Biochemical
Plant Pathology. The geneticist
completed her undergraduate
studies at the Beijing University.
In 2012 she received a China
Scholarship Council Award for
her dissertation at Helmholtz
Zentrum München.
Tao Xu came to Munich upon
recommendation of his Chinese
supervisor. Jiao Tong University
Shanghai, where Xu completed
a Master’s degree in Biostatistics and Bioinformatics,
collaborates closely with the
Research Unit Molecular Epidemiology at Helmholtz Zentrum
München. For his dissertation,
Tao Xu is investigating the
relationship between metabolic
profile, cardiovascular diseases
and the influence of smoking.
The results of his research have
already been published in several international publications
(page 92).
Christina Dargel is a member of
the Helmholtz Graduate School
Environmental Health and the
Medical Graduate Center l of
At the Institute of Virology she
is working on the development
of an immunotherapy for the
treatment of liver cancer. As
spokesperson for the doctoral
students, Christina Dargel proposed and supported an event
format that provides insight
into the day-to-day work of
scientists in industry. A former
Konrad Adenauer Scholar, she
studied biology and pharmaceutical sciences at Munich’s
elite universities. She spent one
semester at the University of
Leiden in conjunction with her
Master’s thesis.
Junior Research
Groups
19
Junior Research Groups
As representative for all research programs, in the following pages
we present six junior research groups.
JUNIOR RESEARCH GROUPS
38 Insights into the World
of Mitochondria
Cellular “power stations” or mitochondria are Fabiana Perocchi’s passion. The
research of the Rome-born scientist revolves around these energy centers of the
cells: Mitochondria are the center stage of energy metabolism and are involved
in many cellular tasks. Mitochondrial dysfunction can lead to a number of
diseases. Fabiana Perocchi investigates the role of mitochondria in cell
signaling. Together with her junior research group “Functional Genomics
of Mitochondrial Physiology and Pathophysiology” at the Institute of
Human Genetics, she is seeking to elucidate the unsolved mysteries
of these organelles.
39 Inconsistencies in scientific models have always fascinated Fabiana Perocchi. “When I
discover a puzzle piece that does not seem to fit into the general concepts of a model,
I get really excited,” the biologist says. “I keep obsessing about it until I’ve figured out
what its function is and how it fits into the context of the whole system.”
Perocchi‘s personal puzzle piece is the signaling network of mitochondria. During her time
as postdoc at Harvard Medical School she wondered why mitochondria can absorb such
a large influx of calcium ions. Perocchi’s curiosity as a researcher was aroused – not least
because the answer to this question might provide relevant insights for medical applications. “Knowledge just for knowledge’s sake is not enough for me,” she stresses. “What’s
important is that knowledge contributes to improving health.
Perocchi found that the calcium supply in the mitochondria is crucially involved in cell
signaling. Because this is disturbed in many common diseases, mitochondrial calcium
signaling could provide a promising target for new therapy options. “Once we have
precisely characterized calcium regulated pathways in mitochondria, we can then
modulate them and develop therapies for diabetes as well as for neurodegenerative
and cardiovascular diseases,” Perocchi says. Her team is currently analyzing the effect
of various active pharmaceutical ingredients on mitochondrial function in order to
subsequently seek new options for future drugs.
From Harvard, Perocchi was attracted to Helmholtz Zentrum München because of the
scientific environment. “Munich is a crucible for excellence in the field of mitochondria
research. The technological infrastructure and the exchange of ideas with colleagues in
related fields have a very positive effect on the advancement of my research,” Perocchi
adds. She also greatly appreciates the support of the administrative departments at the
Center: “Here I can concentrate completely on my research – I have the feeling that a
whole network of departments is behind me.
BRIEF PROFILE
DR. FABIANA PEROCCHI
since 2013:
Emmy Noether Junior Research
Group Leader at the Institute of
Human Genetics, Helmholtz
Zentrum München and (since
2012) BioSysNet Research
Group Leader at the Gene
Center of Ludwig-MaximiliansUniversität München
2011-2012:
Senior Postdoctoral Fellow,
Centre for Genomic Regulation,
The European Molecular
Biology Laboratory (EMBL),
Barcelona, Spain
2008-2011:
Postdoc, Harvard Medical
School and Massachusetts
General Hospital, Boston, USA
2007:
PhD, European
Molecular Biology Laboratory
Heidelberg
What Perocchi considers to be most important for her research group is a spirit of
cooperation. “Success cannot be achieved if research is conducted in isolation,” she
points out.
Everyone in the team must be motivated, curious and independent and at the same
time be open to ideas and objections from colleagues. Fabiana Perocchi: “Today
research is a dynamic field. Only if you integrate the insights of colleagues into your
own considerations can you keep pace with developments and transfer basic research
findings into medical applications.”
Fabiana Perocchi’s research interest is intracellular signal transduction with
a special focus on mitochondria and their calcium signaling network (image).
Mitochondria are critically involved in intracellular signaling.
www.helmholtz-muenchen.de/
en/research/research-excellence/
portraits-of-researchers/
dr-fabiana-perocchi
40 Peacekeeping Troops of the
Immune System against
Type 1 Diabetes
Carolin Daniel compares research to studying a mosaic: “If you look at it from
a distance, you see a coherent picture. However, viewed up close, in each
single mosaic piece you will find another hidden mosaic that first must be
elucidated in detail.“ For Carolin Daniel and her junior research group
“Immunological Tolerance in Type 1 Diabetes” at the Institute of Diabetes Research, the overall mosaic is type 1 diabetes, and the special
mosaic piece is the role of regulatory T cells, the so-called peacekeeping troops of the body’s own immune system.
41 More and more children are being diagnosed with type 1 diabetes. In this autoimmune
disease the body’s own immune cells gradually destroy the insulin-producing beta
cells of the pancreas. The disease could be markedly reduced if Carolin Daniel succeeds
in applying to humans what she has already achieved on a model organism as a
postdoc in Boston: By means of an insulin variant she has induced regulatory T cells
to protect the beta cells against an attack of the body’s own immune system, thereby
leading to the prevention of type 1 diabetes.
Daniel’s objective is to translate this breakthrough in immunology from the animal model
to benefit human patients. Together with her team of five, she is seeking to develop a
vaccine that can prevent the onset of type 1 diabetes in childhood.
The disease has a strong genetic component, which is likely triggered by environmental factors. The main trigger, however, is ultimately a false reaction of the immune
system in which the produced immune cells do not distinguish between foreign and
endogenous components. Normally in such a case, regulatory T cells move to the scene
and prevent an attack on the body’s own cells. Daniel therefore refers to the regulatory
T cells as the “blue helmets, the peacekeeping troops of the immune system”. However,
in type 1 diabetes, sufficient numbers of these “blue helmets” are lacking to carry out
this function. The beta cells in the pancreas that produce insulin can be destroyed over
a period of time by the pathologically activated immune cells.
Daniel‘s therapy concept is to strengthen the peacekeeping troops: It is based on
converting naive T cells into regulatory T cells with respect to the specific antigen. In
this case, insulin functions as the antigen. That is why researchers first attempted to
generate regulatory T cells via stimulation with low doses of insulin. This method proved
to be inefficient, and the researchers subsequently used higher doses of insulin. Daniel
laughs: “That went according to the motto “more helps more”. In fact, through this
method diabetes was partially triggered in the model – but regulatory T cells could
not be efficiently produced.”
Instead of quantity, Daniel focused on quality. She developed an insulin variant, which
has now been patented, in which a low dose actually leads to the desired result. With
her team, the immunologist is now working from an insulin mimetic compound modeled after the natural epitope to develop an equivalent vaccine for humans.
Daniel is convinced that Helmholtz Zentrum München offers her the best conditions to
achieve her goal. Here she has access to extensive data and biological samples from
children and adults. The material was collected by the director of the Institute of Diabetes Research, Anette-Gabriele Ziegler, in part over a period of 20 years. “The data and
samples are a gold mine for research and are essential to develop strategies for the
prevention of type 1 diabetes and autoimmunity,” Carolin Daniel points out.
Carolin Daniel explores strategies for the prevention of autoimmune diseases such as
type 1 diabetes. A vaccine she developed, which mimics natural insulin, stimulates the
formation of regulatory T cells (stained blue in the image), which protect the insulin-producing islet cells (green) against the attack of the immune system.
BRIEF PROFILE
DR. CAROLIN DANIEL
since 2012:
Leader of the junior research
Group Immunological
Tolerance in Type 1 Diabetes at
Helmholtz Zentrum München
2011:
Research awards of the Juvenile
Diabetes Research Foundation
(JDRF) and the Boston Area
Diabetes Endocrinology
Research Center (BADERC)
2008-2012:
Postdoc, Dana Farber Cancer
Institute and Harvard Medical
School Boston, fellowship
of the National Academy of
Sciences Leopoldina
2008:
Fritz Kuelz Prize of the German
Society for Pharmacology
and Toxicology
2007-2008:
Postdoc, Institute of Pharmacology/Immunopharmacology
of Goethe University Frankfurt
am Main
2006:
Research prize of the RhineMain Society of Gastroenterology
2003-2007:
Karolinska Institutet Stockholm
and Goethe University Frankfurt am Main,
PhD fellowship of the German
Research Foundation,
PhD degree (2008)
dr-carolin-daniel
42 Communication Factors
under Surveillance
Unusual ideas are welcome in Stefanie Eyerich’s team. “They are inspiring and lead
to new approaches,” says the leader of the junior research group “T Cell Biology
in Health and Disease” at the Institute of Allergy Research of Helmholtz Zentrum
München. Stefanie Eyerich also pursues new approaches to help patients
suffering from atopic eczema and psoriasis. She is exploring the role that
various T cells play for the barrier function of the skin and is searching
for new drug targets.
43 Every day in her practical work, it is clear to Stefanie Eyerich how important it is to
develop new therapy options for inflammatory diseases of the skin. “The patients have
a very high level of suffering. My goal is to improve their quality of life,” explains the
immunologist. Atopic eczema and psoriasis are among the most common diseases of
the skin. In Germany around four million people are affected by atopic eczema, most of
them children; an additional three million people have psoriasis. An imbalance in the
immune system underlies both diseases and leads to the appearance of the symptoms.
T cells, which actually fulfill protective functions in the immune system, play an
important role in the disease process. T cells, also called T lymphocytes, initiate an
immune response in the body as soon as they come into contact with substances that
they recognize as foreign. Certain T lymphocytes remember such a specific immune
response and when they encounter the same foreign substance at a later time, they
trigger a rapid and effective immune response. If the immune system, however, gets
out of balance, it classifies the body’s own structures or harmless structures from the
environment as dangerous. This leads to an increased release of cytokines, which
then trigger allergic and inflammatory reactions.
BRIEF PROFILE
DR. STEFANIE EYERICH
since 2013:
group T Cell Biology in Health
and Disease at the Center for Allergy and Environment (ZAUM)/
Institute of Allergy Research,
Technische Universität and
2013:
Robert Koch Postdoctoral
Award for Immunology,
ACTERIA Early Career Research
Prize for Allergology
2012:
Dr. Ernst Wiethoff Prize
Together with her team, Stefanie Eyerich analyzes which specific T cells trigger this
reaction. The main focus is on the communication factors of the T cells, the cytokines.
These interact with epithelial cells in the tissue and instruct them to initiate an inflammatory reaction. The team wants to understand which communication factors are
produced so that they can be deactivated with the aid of antibodies. Then, in this case,
the command to trigger an inflammatory reaction would not be given. The onset of the
disease could be prevented, and the patients could be helped effectively.
2011:
Egon Macher Prize of the
Association of Dermatological
Research
“For me it was always important to do research that is medically relevant,” the biologist stresses. The Institute of Allergy Research provides an ideal environment for this:
Two colleagues in Eyerich‘s team work as doctors in the Clinic for Dermatology and
Allergology of Technische Universität München and at the same time conduct research
in the laboratory. “We can analyze T cells directly from patient samples and include
observations from practice in our research,” says the scientist.
2009:
Science Prize of the German
Mycological Society
Already during her time as postdoc at Imperial College in London, Eyerich’s primary
research interest was immunology and allergy. One of the most valuable experiences
she gained from her work there in the large laboratory was “the ‘intensively lived’
interdisciplinary communication“. She found these communication structures again at
Helmholtz Zentrum München – another reason “why research here is fun“. From her
staff members she also expects “that they are motivated and enjoy doing their tasks“.
Stefanie Eyerich herself finds it especially motivating to pass on her knowledge to young
team members, in order to develop projects together to lead to success.
2008-2009 :
Postdoc, National Heart and
Lung Institute (NHLI), Department of Allergy and Clinical
Immunology, Imperial College
London, UK
Stefanie Eyerich wants to elucidate the immunological causes of inflammatory skin
diseases such as atopic eczema and psoriasis. Her junior research group is focusing on
the cytokines of specific T cells, which react with skin cells (the image shows a keratinocyte) and which trigger inflammatory reactions.
2010-2012:
Assistant to the group leader,
Center for Allergy and Environment
2009-2010:
Postdoc, Center for Allergy and
Environment
2008:
PhD degree, Technische
Universität München
dr-stefanie-eyerich
44 Searching for
the Origin
His home is always where top scientists collaborate to discover how stem cells
develop into the specialized cell types that our body is consisted of. Micha
Drukker already conducted research on this topic at The Hebrew University
in Israel and at Stanford University in the U.S. Since 2012 he has headed the
junior research group “Human Pluripotent Stem Cell Lineage Choice”
at the Institute of Stem Cell Research at Helmholtz Zentrum München –
and feels as if he has arrived home. “I was already acquainted
with my colleagues and knew that this is an ideal environment
to study fundamental questions and translate the findings for
studying development of multifactorial diseases.”
45 Already as a child, Micha Drukker was fascinated with the question of our own creation:
How does a finely coordinated system of organs develop from a single fertilized ovum?
How do molecular interactions between organs mediate development? Trying to find
the answer to this is what drives Drukker in his research.
The biologist specializes in the study of stem cells. They offer the possibility to study in
the lab the development of undifferentiated cells, not yet specified to serve particular
functions, into tissues and thus to come closer to solving the question of how we are
made to become what we are. Drukker uses two cell types for his research: embryonic
stem cells and somatic cells. The latter he reprograms back to their original state, so
that they, too, are pluripotent. Then by applying signals and factors they can be instructed to develop into any cell type. Using embryonic stem cells, the scientist defines
precisely when pluripotent cells develop into specialized cells and which mechanisms
and molecules are responsible for this. “When we have analyzed these processes, we
can open up a wide area of medical applications,” says Drukker.
At Stanford University he developed a technique with which tissue progenitor cells can
be isolated very efficiently from mixed cultures of differentiating stem cells. Using this
technique at Helmholtz Zentrum München, he is now focusing on purifying tissueregenerating cells from pluripotent stem cells, including beta cells for the therapy of
type 1 diabetes patients. ” My goal is to replace functionless or inefficiently working
cells in diabetes or Parkinson patients with functioning cells,” the scientist explains.
BRIEF PROFILE
DR. MICHA DRUKKER
since 2012:
group Human Pluripotent Stem
Cell Lineage-Choice Research
and the Human Induced Pluripotent Stem Cell Unit at the
Institute of Stem Cell Research,
2010-2012:
Research associate,
Stanford University, USA
2005-2010:
Postdoctoral fellowship,
Stanford University, USA
2005:
PhD degree, The Hebrew
University, Israel
Using the second cell type, the reprogrammed skin cells, Drukker wants to find out
how normal pluripotent cells differ from those of the patient samples: “Reprogrammed
cells are well suited to study in vitro where the switches are set for the development
of multifactorial diseases such as diabetes or neurodegenerative diseases.“
The research group leader also offers expertise and techniques to other scientists.
He is convinced that research today can only succeed when the experts of various
specialized areas work together in synergy. “The days of the generalists are over,” he
stresses. That is why he especially appreciates the fact that a broad scientific spectrum
can be encountered directly at the Center. “I work here like in a kibbutz: My colleagues
and I are a great community, who are together attempting to understand the question of
life emergence. Everyone is at the top of his or her field. That inspires me,” says Drukker.
The aim of Micha Drukker is to provide cures for diseases by means of induced pluripotent stem cells. His team reprograms cells from patients affected with diabetes and
Parkinson’s disease (image) with the aid of mRNA molecules encoding specialized sets
of transcription factors .
dr-micha-drukker
46 Proteins under the
Hammer
Proteins are the building blocks of life. If something goes wrong during their production, diseases such as diabetes, cancer and neurodegenerative changes can
be the result. Using state-of-the-art equipment, Tobias Madl and his ten-member
team of the junior research group “Structural Biology of Signal Transduction”
are searching for the molecular causes of such production errors.
47 During his studies, Tobias Madl was also interested in physics, computer science and
history. Whether in historical archives or in the chemistry lab – the main objective for
the future chemist was to break new ground and to close knowledge gaps. “To have
new things to discover and to thus benefit mankind, that’s what drives me forward,”
he says, describing his motivation. For him it is important to have the freedom to look
right and left. “That is not a waste of time, but rather serves a purpose.”
Madl‘s Team is based at the Institute of Structural Biology (STB) and the Bavarian
NMR Center, which is run jointly by Technische Universität München and Helmholtz
Zentrum München. The group maintains close cooperation on various levels. In collaboration with the Institute of Molecular Cancer Research at the University of Utrecht,
the researchers explore how signal transductions are influenced by defective proteins
and by the environment, e.g. oxidative stress, thus leading to the development of
cancer. Together with the Ludwig-Maximilians-Universität München and the German
Center for Neurodegenerative Diseases, the role of RNA-binding proteins is analyzed
in the regulation of signal transduction. And finally, with partners from the University
of Tübingen, the group checks whether the molecular and cell biological findings are
confirmed in clinical studies. “These collaborations make it possible to bridge the gap
between the disease and the molecular causes," says Madl, describing the synergy.
For the first step, the characterization of the proteins, the group in the Bavarian NMR
Center has access to state-of-the-art NMR spectroscopy equipment. Using these devices,
Madl analyzes the spatial structure and the interaction of the protein areas. To explain
the highly complex method, the chemist illustrates it with a comparison: “We hit with
a hammer on the atoms in the molecules and listen as they scream. From the data
on the location and strength of the scream we can derive the spatial structures of the
proteins and investigate interactions between the protein areas.”
BRIEF PROFILE
DR. TOBIAS MADL
since 2012:
Emmy Noether Junior Research
Group Leader at Helmholtz
Zentrum München and Junior
Fellow at Technische Universität
München; APART fellow at the
University of Utrecht and
University of Graz
2012:
Science Prize of the
Austrian Chemical Society
2010–2011:
Postdoc, University of Utrecht
2008:
Schrödinger Fellowship of the
Austrian Fund to Promote
Scientific Research
2007–2010:
Postdoc, Institute of
Structural Biology, Helmholtz
Zentrum München and Tech
nische Universität München,
EMBO Fellowship
2007:
PhD degree, postdoc
University of Graz
To obtain information regarding the form of the biomolecules complementary to the
NMR spectroscopic data, the team uses the SAXS system to measure the small angle
X-ray scattering. Using a program Madl developed, these data are combined with the
NMR data to obtain the structural and dynamic characteristics of the target protein.
Step by step, the researchers are now beginning to study the individual elements in
detail. Their aim is to find out which structures are responsible for the development
of diseases and which could serve as potential drug targets.
To elucidate the interactions between proteins and other cell organelles, different
methods must be combined. “I am therefore glad that at Helmholtz Zentrum München
there is a great concentration of outstanding biological research. Here I can also study
how environmental factors regulate proteins and whether they are responsible for
dysregulations“, says Madl. In his opinion, scientific exchange with other research
groups is essential to answer these challenging questions. Besides scientific expertise,
the research group leader therefore places emphasis on social competence: “We are
happy to measure ourselves against external competition. But within the team there is
no place for this – we all are dependent on each other and benefit from each other.”
Tobias Madl investigates the spatial structures of proteins that transmit signals between
cells. He wants to find out how defective proteins transmit signals between cells (in the
image transportin), leading to the development of diseases.
dr-tobias-madl
48 Signals for the
Protection of Plants
Corina Vlot-Schuster discovered her fascination with plant immune defense early
in her career. During her time at the Boyce Thompson Institute in the U.S. and at
the Max Planck Institute for Plant Breeding Research in Cologne, she explored
systemic acquired resistance in Arabidopsis thaliana, thale cress. This model
plant is also well established at Helmholtz Zentrum München. When she
was offered the opportunity to lead the junior research group “Inducible
Resistance Signaling” at the Institute of Biochemical Plant Pathology,
Vlot-Schuster did not hesitate to accept.
49 Corina Vlot-Schuster‘s area of research is a special form of plant defense called systemic
acquired resistance (SAR). Although plants do not produce any antibodies, they can react
to locally limited attacks of pathogens with a kind of long-term immunity: Cells die off
around the affected area and prevent the spread of the infection. At the same time signal
substances are emitted that lead to an increase of resistance in the entire plant and
protect against a wide range of pathogens.
This mechanism has been extensively studied in thale cress. Corina Vlot-Schuster
showed that SAR also protects barley from invading pests such as bacteria. Together
with her six-member team, the Dutch-born scientist wants to characterize the involved
signaling molecules in this agriculturally important grain plant and to protect this and
other crops against pests in the future with the plant’s natural defense substances.
“SAR is very attractive for use in crop agriculture. Since the plant hardly uses resources
for this kind of defense, the crop yield is not adversely affected,” explains Vlot-Schuster.
To identify key molecules that are responsible for triggering the mechanism, the plant
physiologist is supported by experts from other fields. For the characterization of the
signal molecules in barley, she benefited from the work of bioinformaticians in the
Research Unit Genome and Systems Biology of Plants: In 2012 they deciphered the entire
barley genome. At Helmholtz Zentrum München Vlot-Schuster conducts her research
quasi next door to these colleagues: “We are on equal footing, and our collaboration is
uncomplicated. We work hand in hand and try to solve problems together.”
BRIEF PROFILE
DR. CORINA VLOT-SCHUSTER
since 2009:
group Inducible Resistance
Signaling, Institute of Bio
chemical Plant Pathology,
2007-2009:
Marie Curie/EMBO Fellow,
Max Planck Institute of
Plant Breeding Research,
Cologne
2003-2006:
Postdoc, Boyce Thompson
Institute of Plant Research,
Ithaca, USA
2003:
PhD degree, Leiden University,
The Netherlands
This type of collaboration also has a profound effect on her team. Vlot-Schuster selected
her staff based on scientific criteria, but also on their social competence. “We discuss
all decisions together,” she says. She expects from her team members that they assume
responsibility and work independently. Vlot-Schuster: “If you want to be successful in
implementing your projects later on, these are core competences.”
The biologist works in a challenging academic environment. “It has become more difficult
to publish results in high-quality, prestigious journals“, she observed – a development
that she finds also has positive aspects: “You set your own bar higher and higher, and this
increases the quality of the research.”
In addition to academic success, however, Corina Vlot-Schuster is also pursuing another
objective: “It has always been important to me that my research can also be applied to
protect the environment and to produce potentially healthier foods.”
Corina Vlot-Schuster wants to use the natural defense mechanisms of plants for the
environmentally friendly production of food crops. Her focus is on signal substances
that are involved in systemic acquired resistance (SAR), which she explores in the
model plant Arabidopsis thaliana (image) and in barley.
dr-corina-vlot-schuster
Conducting Research
within Strategic
Programs
SPEAKERS:
POF
Program-Oriented
Funding
Research activities at Helmholtz Zentrum München are linked thematically
and with regard to content through strategic programs of the Helmholtz
Association and are financed through program-oriented funding (POF).
Complex questions and problems relevant to science, society and the
economy can thus be explored across institutional and disciplinary borders.
GenCoDe Program
Prof. Dr. Wolfgang Wurst
wurst@
helmholtz-muenchen.de
T 089 3187 4111
GEnCoDe
TE
Genes and Environment
in Common Diseases
Terrestrial
Environment
With the program “Genes and Environment
in Common Diseases”(GEnCoDe), Helmholtz
Zentrum München is assuming a leading role in
innovative health research. The aim of GEnCoDe
is to elucidate gene-environment interactions
and their significance in the pathogenesis of
common diseases, in particular diabetes, lung
diseases and allergies. The GEnCoDe program is
linked beyond the borders of various disciplines.
It brings together the successful predecessor
programs “Environmental Health” and “Systemic
Analysis of Multifactorial Diseases” and generates
additional synergies for the elucidation of the
underlying mechanisms of major common diseases and their prevention, diagnosis and therapy.
Besides Helmholtz Zentrum München, which
coordinates GEnCoDe, the Helmholtz Centre for
Environmental Research (UFZ), Leipzig, has a
seven percent stake in the project. The scientific
content of the program is divided into five topics.
Helmholtz Zentrum München concentrates its
environmental research in the program “Terrestrial Environment” (TE). The Center focuses on
the areas of plant defense and stress resistance,
water quality, control of ecosystems and the
prevention of environment-related diseases.
Helmholtz Zentrum München collaborates closely with the Helmholtz Centre for Environmental
Research (UFZ), Leipzig, which coordinates the
program, and Forschungszentrum Jülich. With a
program share of 23 percent, Helmholtz Zentrum
München is engaged in three of the five topics.
In the research area Health, Helmholtz Zentrum
München is involved in all cross-disciplinary
activities. Helmholtz Zentrum München and
four additional Helmholtz health centers have
joined together in the association Personalized
Medicine. In the research field Earth and the
Environment the Center participates in the
cross-disciplinary topics and associations
Bioeconomics, Climate Research and Water.
1
Systemic analysis of genetic
and environmental factors that
impact health
2
Diabetes: pathophysiology,
prevention and therapy
2
Sustainable
plant production
3
Chronic diseases of the lung
and allergies
3
Sustainable
water management
4
Mechanisms of genetic and
environmental influences on
health and disease
5
New technologies for
biomedical discoveries
4 P rof. Dr. Magdalena Götz
magdalena.goetz@
T 089 3187 3750
5 Prof.
Dr. Vasilis
Ntziachristos
v.ntziachristos@
T 089 3187 3852
TE Program
5
Terrestrial systems: from the
observation to the prediction
CROSS-DISCIPLINARY ACTIVITIES
Personalized Medicine
2 Prof.
Dr. Matthias Tschöp
matthias.tschoep@
T 089 3187 2103
3 Prof.
Dr. Oliver Eickelberg
oliver.eickelberg@
T 089 3187 4666
TOPICS
Within the framework of program-oriented
funding, Helmholtz Zentrum München is
integrated into the two research fields: “Health”
and “Earth and Environment”. Following the
successful review in the field of Health, the
Center is continuing to focus on the investigation
of major common diseases. In the third POF
phase beginning in 2014, the Center is pooling
its resources in the health program GEnCoDe
(Genes and Environment in Common Diseases).
In the field of Earth and Environment, the Center
is conducting research in the program Terrestrial
Environment (TE).
1 Prof.
Dr. Martin
Hrabe de Angelis
hrabe@
T 089 3187 3302
Bioeconomics:
climate research, water
Strategic Partnerships
Allergy, Microbiome and Climate Research
2 Prof. Dr. Jörg Durner
durner@
T 089 3187 3434
3 Prof.
Dr. Rainer
Meckenstock
rainer.meckenstock@
T 089 3187 2560
5 Dr.
Eckart Priesack
priesack@
T 089 3187 3354
RESEARCH
HIGHLIGHTS
2240
publications in 2012 and 2013
From the publications of the last two years we present 34 scientific highlights.
HIGHLIGHTS 2012/2013
54 BRIEF PROFILE
DR. TIMO MÜLLER
Leader of the research group
Molecular Pharmacology
at the Institute for Diabetes and
Obesity, Helmholtz Zentrum
München
2011: Outstanding Young
Investigator Award of the
American Society for Clinical
Investigation/ American
Academy of Pediatrics
2008–2011: Postdoc at the
Metabolic Diseases Institute,
University of Cincinnati,
Ohio, USA
2005-2008: PhD at the
University of Duisburg-Essen
55 Brain Signal Regulates
Body Weight
Scientists of the Institute for Diabetes and Obesity,
in collaboration with partners from the Charité
– Universitätsmedizin in Berlin, have discovered
that a receptor in the brain whose function was
largely unknown until now is involved in the
regulation of body weight. As the research group
led by Timo Müller has shown for the first time,
the molecule Gpr83 (G protein-coupled receptor
83) plays a crucial role in the regulation of energy
balance. Thus, mice with a loss of function of this
receptor are protected from obesity and diabetes,
even after being fed a high-fat diet.
The regulation of body weight is a complex
process in which organs such as the gastrointestinal (GI) tract and adipose tissue are in constant
cross-talk with the brain about the current energy
status. The brain responds to the GI signals with
an activation or inhibition of neuronal signaling
mechanisms that control the sensation for hunger
and satiety. One of these signals is the hormone
ghrelin which, produced in the stomach, reaches
the brain via the bloodstream. In the brain,
ghrelin activates regulatory circuits that control
food intake. As the scientists found out, Gpr83
affects energy metabolism both via direct interaction with the ghrelin signaling pathway as well
as via not yet identified ghrelin-independent
signaling mechanisms. In further studies, specific
binding partners of Gpr83 shall be identified.
The researchers thus hope to obtain new
strategies for the treatment of obesity and
diabetes. If blocking Gpr83 proves to be a safe,
targeted approach, this could lead to new
pharmacotherapies to treat metabolic diseases.
Ghrelin
Fasting
Gpr83
Ghsr
Ghsr
cell membrane
Food intake
Ghrelin
Gpr83/Ghsr
heterodimer
Original Publication:
Timo D. Müller et al.: The
Orphan Receptor Gpr83 Regulates Systemic Energy Metabolism via Ghrelin-Dependent and
Ghrelin-Independent Mecha
nisms. Nature Communications
4 (2013) 1968 | doi: 10.1038/
ncomms2968
Further authors from
Helmholtz Zentrum München:
Chun-Xia Yi, Carola W. Meyer,
Brian Finan, Kerstin Stemmer,
Paul T. Pfluger, Matthias H.
Tschöp – Institute for Diabetes
and Obesity
Susanna Hofmann – Institute of
Diabetes and Regeneration
Research
The Gpr83 receptor expressed in the brain plays a crucial role in the
regulation of body weight. The new finding that Gpr83 influences
body weight through an interaction with the appetite-stimulating
hormone ghrelin, among other means, constitutes an important
contribution to the elucidation of the signaling networks involved in
the control of body fat and glucose metabolism.
Ghrelin is a hormone primarily produced in the gastric mucosa that
has an appetite-stimulating effect. In the fasting state, ghrelin levels
rise in the blood and decrease again after each meal. In addition to
the regulation of food intake, ghrelin has a number of other effects
such as the stimulation of growth hormone secretion.
cell membrane
Fasting reduces the expression of the brain receptor Gpr83 in the hypothalamus. Its d
imerization
with the ghrelin receptor Ghsr is thereby reduced, and ghrelin can stimulate food intake by
binding to Ghsr. Food intake increases the expression of Gpr83. More Gpr83-Ghsr heterodimers
are formed, and the ability of ghrelin to activate the ghrelin receptor is reduced.
56 BRIEF PROFILE
DR. BRIAN FINAN
Drug Discovery at the Institute
for Diabetes and Obesity,
2012-2013: Postdoc, Institute
for Diabetes and Obesity,
2006-2012: Scientific staff
member, Indiana University,
Bloomington, USA
2011: PhD degree
Brian Finan et al.: Targeted
Estrogen Delivery Reverses the
Metabolic Syndrome. Nature
Medicine 18 (2012) 1847-56 |
doi: 10.1038/nm.3009
Kerstin Stemmer, Timo D.
Müller, Chun-Xia Yi, Sonja C.
Schriever, Cristina GarcíaCáceres, Dhiraj G. Kabra, Paul
Pfluger, Matthias H. Tschöp –
Institute for Diabetes and
Obesity
Wolfgang Hans, Martin Irmler,
Johannes Beckers, Martin
Hrabe de Angelis – Institute of
Experimental Genetics
57 Hormones against
Metabolic Syndrome
Scientists of the Institute for Diabetes and
Obesity together with U.S. cooperation partners
have succeeded in using tissue-specific drugs
to target metabolic syndrome, a pre-existing
condition of type 2 diabetes. They selectively
directed estrogen to specific cell types by
binding it to the gut hormone GLP-1 (glucagonlike-peptide 1), thereby causing the symptoms
of metabolic syndrome to diminish.
If the hormone estrogen is chemically conjugated to the gut hormone GLP-1, the estrogen
merely passes into the GLP-1 target cells, but
not into estrogen-sensitive organs such as the
uterus. With this novel conjugate between a
peptide and steroid hormone the scientists
showed in the animal model that estrogen can
maximize the effect of GLP-1 in reducing levels
of blood glucose and in loss of body fat, but for
the first time without the negative side effects
of estrogen on the uterus and without elevated
tumor risk. The trick is that the gut hormone
only delivers the conjugated estrogen to certain
cell types. On the basis of GLP-1, drugs have
been developed that are already approved for
the treatment of type 2 diabetes. In the animal
model, both in the treatment of obesity as well
as type 2 diabetes, the novel conjugate shows a
significantly better effect than GLP-1 alone.
Metabolic syndrome, obesity and type 2 diabetes
are increasing in Germany and worldwide in
epidemic proportions, thus presenting major
challenges to the health system. Therefore new
and effective therapy concepts with minimal side
effects are urgently needed, especially for these
forms of the disease. The conjugate approach
may represent a completely new treatment concept which may similarly be applied to a number
of other diseases that may likewise be influenced
by steroid hormones.
Hormone Duo Promotes
Loss of Fat Reserves
The interaction of the two hormones glucagon and fibroblast growth factor 21 (FGF21)
has a decisive impact on lipid metabolism and
body weight. Their coordinated action leads
to decreased food intake and increased fat
burning, as scientists of the Institute for Diabetes
and Obesity in cooperation with the Metabolic
Diseases Institute of the University of Cincinnati,
USA, discovered. The two neurotransmitters are
thus considered to be promising target structures for treating obesity and type 2 diabetes.
As “hunger hormone”, glucagon mediates a
reduction of the energy reserves of the body. For
the first time, the scientists found that the direct
interaction with the neurotransmitter FGF21 is
required for this effect. The team led by Kerstin
Stemmer and Matthias Tschöp studied the
long-term effect of glucagon in a mouse model
and showed that this effect is characterized by
decreased food intake, increased fat burning and
decreasing cholesterol levels. At the same time
there was a significant increase in the hormone
FGF21. This effect could be detected not only
in mice but also in humans. If the mice lacked
FGF21 due to a genetic defect (FGF21 knock-out
mice), glucagon lost its positive properties on
metabolism. From this the scientists infer that
FGF21 is essential for the effects mediated by
glucagon on fat burning and cholesterol levels.
The results support earlier work by the team
according to which fusion hormones from
glucagon and glucagon-like peptides (e.g. glucagon-like-peptide 1, GLP-1) have a significant
potential for the treatment of obesity and diabetes. Until now, however, the signaling pathway
was unknown through which glucagon reduces
fat reserves. In further studies the details of the
hormonal interaction of glucagon and FGF21
shall be explored to examine potential applications for the treatment of metabolic diseases.
By conjugating the gut hormone GLP-1 with estrogen, scientists
succeeded in the animal model to direct this peptide-steroid c onjugate
to specific tissues. There it caused a reduction of the symptoms of
metabolic syndrome without triggering the negative side effects of
estrogen.
Due to the coordinated action of the two hormones glucagon and
fibroblast growth factor 21 (FGF21), there is a decreased food
intake and increased fat burning. Therefore, the two substances are
considered to be potential targets for the treatment of metabolic
diseases such as obesity and type 2 diabetes.
The metabolic syndrome describes the simultaneous occurrence
of multiple disease symptoms such as obesity, elevated fasting glucose
and blood lipid levels, and high blood pressure.
This combination increases the risk of atherosclerosis, diabetes and
heart disease.
The main task of the peptide hormone glucagon, which is formed in
the alpha islet cells of the pancreas, is to increase the blood glucose
level. When blood glucose levels drop, glucagon is released into the
blood stream and is the counter-regulatory hormone opposing insulin
action in glucose and lipid metabolism.
BRIEF PROFILE
DR. KERSTIN STEMMER
Metabolism and Cancer at the
München
2010-2012: Guest scientist at
the Woods/Seeley Obesity
Research Laboratory, Metabolic
Diseases Institute, University of
Cincinnati, USA
2008-2010: Deputy leader of
the research group Human and
Environmental Toxicology,
University of Konstanz
2008: PhD degree
member, Max Delbrück
Center for Molecular
Medicine Berlin and German
Institute of Human Nutrition,
Potsdam-Rehbrücke
Kirk M. Habegger et al.:
Fibroblast Growth Factor 21
Mediates Specific Glucagon
Actions.
Diabetes 62 (2013) 1453-1463 |
doi: 10.2337/db12-1116
Timo Müller, Paul T. Pfluger,
Matthias H. Tschöp – Institute
for Diabetes and Obesity
Susanna Hofmann – Institute of
Research
58 BRIEF PROFILE
PROF. DR. MATTHIAS TSCHÖP
Scientific speaker of the
Helmholtz Diabetes Center
(HDC) and director of the
Obesity at Helmholtz Zentrum
München, chair of Metabolic
Diseases at Technische
(Alexander von Humboldt
professorship)
since 2012: Adjunct professor,
Yale University (USA)
2003–2011: Professor of
Endocrinology at the Institute
of Metabolic Diseases and
scientific director of the
Diabetes and Obesity Center at
the University of Cincinnati
2002–2003: Research group
leader at the German Institute
of Human Nutrition Potsdam-
Rehbrücke (DIfE)
1999–2002: Postdoc in an
international pharmaceutical
company in the U.S.
59 Efficacy Prognosis
for Gastric Bypass
Gastric bypass is one of the most frequently performed surgical procedures used to treat obesity
and leads to a rapid loss of body weight in most
patients. In addition, the surgical intervention
induces an improved glucose metabolism –
even before the weight loss. These metabolic
improvements, however, vary considerably from
patient to patient.
A hormone test could possibly predict to what
extent a gastric bypass would improve metabolism. Scientists led by Matthias Tschöp of the
Institute for Diabetes and Obesity at Helmholtz
Zentrum München and Kirk Habegger at the
Metabolic Disease Institute of the University of
Cincinnati discovered this using an animal model.
After gastric bypass surgery the concentration of
the gut hormone GLP-1 (glucagon-like-peptide 1)
in the blood rises significantly. GLP-1 increases
insulin secretion and contributes to improved
blood glucose levels and blood lipids. As the scientists led by Tschöp and Habegger showed, the
efficacy of the secreted GLP-1 on blood glucose
levels varies: the higher the sensitivity of the rats
in the animal model to GLP-1, the more effective
the gastric bypass.
GLP-1 sensitivity could thus serve as a new predictive biomarker for personalized therapeutic
approaches for type 2 diabetes and obesity.
If the results are confirmed in the patient trials,
the hormone response could be tested prior
to a planned gastric bypass to determine to
what extent the patient would benefit from the
surgical procedure.
The response to the hormone GLP-1 (glucagon-like-peptide 1), which is
formed in the gastrointestinal tract, can predict the efficacy of a gastric
bypass. GLP-1 sensitivity could therefore be used as a new biomarker
for personalized therapeutic approaches in patients with type 2
diabetes and obesity.
Kirk M. Habegger et al: GLP-1R
Responsiveness Predicts
Individual
Gastric Bypass Efficacy
on Glucose Tolerance in Rats.
Diabetes (2013) Nov 1. [Epub
ahead of print] | doi: 10.2337/
db13-0511
Timo D. Müller, Paul T. Pfluger –
Obesity
In a gastric bypass, only a small remnant of the stomach that
holds about 15 ml remains. Furthermore, the upper small intestine
is bypassed. The digestive juices are introduced into the deeper
portions of the intestine where digestion begins. As a result, only
part of the food is absorbed. The undigested food is conveyed into
the large intestine.
Evolution of
Energy Metabolism
Scientists of the Institute for Diabetes and Obesity, together with colleagues of the University
of Marburg and the Medical Research Council,
Cambridge, UK have found that thermogenesis
in the brown adipose tissue of mammals is an
ancient mechanism.
Brown adipose tissue serves mammals in the
generation of heat by burning fat reserves. The
ability to maintain high body temperatures without shivering – i.e. without the physical work of
muscles – has played an important evolutionary
role for the colonization of cold habitats but
presumably also for reproduction. The team
led by Martin Jastroch and Carola Meyer of the
Institute for Diabetes and Obesity was able to
demonstrate that fully functional brown adipose
tissue developed at an early stage in mammalian evolution. To this end, the researchers
studied Madagascan Lesser hedgehog tenrecs
(Echinops telfairi), a species that diverged from
modern mammals long ago. Tenrecs display
primitive thermoregulatory features as they do
not maintain a constant high body temperature.
However, they have brown adipose tissue and
active uncoupling protein 1 (UCP1), the latter
being essential for burning fats. The scientists
conclude that fat burning is a physiological
process that developed early in evolution, independent of sustained body temperatures. The
study allows a new view on energy metabolism
with regard to evolution and the functionality
of brown adipose tissue. The scientists intend
to broaden technological advances of this study
to characterize brown adipose tissue to identify
novel activators of fat burning. Of particular interest are the uncoupling proteins such as UCP1,
which are crucially involved in the balance of
energy metabolism. Translating the fundamental
findings on brown adipose tissue function, their
studies will assist in developing new therapeutic
concepts to increase fat burning , thus reducing
excess fat reserves, e.g. in obesity.
Lesser hedgehog tenrecs – higher mammals that do not have constant body temperature – allowed the scientists to conclude that fat
burning is a physiological process that was developed early in mammalian evolution, possibly prior to sustained high body temperature.
Brown adipose tissue is a special form of fat tissue, whose cells
are able to generate heat by oxidation of fatty acids (thermogenesis).
This occurs in numerous mitochondria, which are also responsible for
the yellow-brownish color of the tissue.
BRIEF PROFILE
DR. MARTIN JASTROCH
Mitochondrial Biology at the
München
2011: Research Recognition
Award of the American
Physiological Society
2009–2011: Research
scholarship of the German
Research Foundation
2008–2011: Postdoc, Buck
Institute for Research on Aging,
Novato, CA, USA
2008: Best PhD thesis award in
biology at the University of
Marburg
2007–2008: Scientific staff
member, University of Marburg
2007: PhD degree, University of
Marburg
2005: Young investigator
competition award “Frontiers
in Thermoregulation”
BRIEF PROFILE
DR. CAROLA W. MEYER
Metabolic Physiology at the
München
2011: Adjunct professor
Zoology/Animal Physiology,
University of Marburg
member and research group
leader in Zoology/Animal Physiology, University of Marburg
2005: PhD degree in
Zoology/Animal Physiology,
University of Marburg
Rebecca Oelkrug et al.: Brown
Fat in a Protoendothermic
Mammal Fuels Eutherian
Evolution.
Nature Communications
4 (2013) 2140 | doi: 10.1038/
ncomms3140
Maria Kutschke, Saskia Müller,
Matthias H. Tschöp – Institute
for Diabetes and Obesity
60 BRIEF PROFILE
DR. RUI WANG-SATTLER
Research group leader,
Research Unit Molecular
Epidemiology, Institute of
Epidemiology II, Helmholtz
Zentrum München
2007-2011: Senior scientist,
Institute of Epidemiology,
2010: Paula and Richard von
Hertwig Prize for Interdis
ciplinary Research
2000-2007: Postdoc,
European Molecular Biology
Laboratory (EMBL)
Rui Wang-Sattler et al.: Novel
Biomarkers for Pre-Diabetes
Identified by Metabolomics.
Molecular Systems Biology
8 (2012) 615 | doi: 10.1038/
msb.2012.43
Zhonghao Yu, Christina Holzapfel,
Harald Grallert, Tao Xu,
Erik Bader, Kirstin Mittelstrass,
Thomas Illig – Research Unit
Molecular Epidemiology
Ana C. Messias – Institute of
Structural Biology
Katharina Heim, Holger
Prokisch, Thomas Meitinger –
Institute of Human Genetics
Monica Campillos, Werner
Roemisch-Margl, Karsten Suhre
– Institute of Bioinformatics
and Systems Biology
Barbara Thorand, Cornelia
Huth, Christine Meisinger,
Annette Peters – Institute of
Epidemiologiy II
Angela Döring, H.-Erich Wichmann – Institute of Epidemiology I
Christian Gieger – Institute of
Genetic Epidemiology
Cornelia Prehn, Martin Hrabě
de Angelis, Jerzy Adamski –
Institute of Experimental
Genetics
Heiko Lickert – Institute of
Research
61 Biomarkers of
Pre-diabetes
Pre-diabetes is the early form of type 2
diabetes, one of the most important common
diseases. Between about eight to ten percent
of the German population suffers from this
disease, and its incidence is increasing rapidly.
In the pre-diabetic stage, the further development of the disease can be largely prevented,
for example by dietary changes or increased
physical activity. Up to now, however, no specific biomarkers have been available to reliably
detect pre-diabetes.
In an interdisciplinary study led by Rui
Wang-Sattler, scientists of the Research Unit
Molecular Epidemiology, in collaboration with
researchers from the Institutes of Structural
Biology, Human Genetics, Experimental Genetics,
Epidemiology II, the Genome Analysis Center
and from partner institutes in the German
Center for Diabetes Research identified three
candidate biomarkers for pre-diabetes, two
of which predicted the risk of the disease in
individuals. Using a metabolomics approach,
they quantified 140 metabolites in 4297 serum
samples of the population-based Cooperative
Health Research in the Region of Augsburg
(KORA) cohort. The results were independently
confirmed from the European Prospective
Investigation into Cancer and Nutrition
(EPIC)-Potsdam study.
As the concentration of the biomarkers in
blood are indicative of pre-diabetes, this study
suggests that preventive measures can be taken
The three metabolites are glycine, acetylcarnitine
C2 and lysophosphatidylcholine (LPC) 18:2.
Acetyl Carnitine C2
Glycine
LPC (18:2)
Metabolite
Enzyme
CAC
CrAT
ALAS-H
cPLA2
Pathway-related
protein
Type 2 diabetesrelated gene
PPAR-
AOX
INS
MAPK1
GR
Activation
Inhibition
Physical
interaction
PPARG
TCF7L2
HNF1A
GCK
IGF1
IRS1
IDE
Transcription
Signaling regulation
Same pathway
Metabolomics studies have revealed that three metabolites are
candidate biomarkers for pre-diabetes – an early form of type 2
diabetes. With the aid of these biomarkers, the disease can be
detected soon enough to halt or even prevent its development.
Metabolomics is the systematic study of the small-molecule
etabolite profiles of an organism. The analysis is performed
m
by means of mass spectrometry or using an NMR spectrometry.
Three candidate biomarkers for pre-diabetes associated with seven type 2 diabetes-related genes.
62 BRIEF PROFILE
DR. HARALD GRALLERT
Epidemiology in the Institute
of Epidemiology II, Helmholtz
Zentrum München
research unit Molecular
Epidemiology and research
group Epidemiology –
Biosamples – Genomics
2007: PhD degree
Original Publications:
Andrew Morris et al.: LargeScale Association Analysis
Provides Insights into the
Genetic Architecture and
Pathophysiology of Type 2
Diabetes. Nature Genetics 44
(2012) 981 -988 | doi: 10.1038/
ng.2383 (DIAGRAM)
Robert Scott et al.: Large-Scale
Association Analyses Identify
New Loci Influencing Glycemic
Traits and Provide Insight
into the Underlying Biological
Pathways. Nature Genetics 44
(2012) 991-1003 | doi: 10.1038/
ng.2385 (MAGIC)
Julia Meyer, Martina MüllerNurasyid, Christian Gieger –
Institute of Genetic
Epidemiology; Thomas Illig,
Norman Klopp – Research Unit
Molecular Epidemiology;
Annette Peters, Barbara
Thorand – Institute of
Epidemiology II
63 Role of Genetics in Type2
Diabetes Pathogenesis
Genome-wide association studies (GWAS) are
an effective method to detect genetic variations
that play a role in the pathogenesis of diabetes
mellitus. These may help identify individuals at
an early stage that have an increased risk of diabetes. Epidemiologists of Helmholtz Zentrum
München therefore also participate in international research consortia such as DIAGRAM
(DIAbetes Genetics Replication and Meta-analysis Consortium) and MAGIC (Meta-Analyses of
Glucose and Insulin-related Traits Consortium),
which investigate the genetic causes of diabetes
by means of GWAS, among other methods. In
the consortia, the genetic association analyses
are centrally coordinated to identify and specify
gene variants with reference to type 2 diabetes
and related metabolic disorders.
Through meta-analyses with large numbers of
individuals (circa 133 000 and almost 150 000
subjects) – also using a newly developed metabochip – 53 gene regions with effects on glycemic
characteristics were identified or confirmed, and
ten gene loci associated with type 2 diabetes
were discovered. According to the scientists
involved in the studies, this high number of
loci is an indication that the development of
diabetes and its preliminary stages is so complex because it is based on many factors, each
contributing only small effects. That is why it is
foreseeable that there will be no single effective
therapy for all patients with diabetes. Rather,
personalized, individually tailored approaches
will be needed to gain control over this major,
widespread disease.
Relationship between
PTSD and Type 2
Diabetes
People who suffer posttraumatic stress disorder
(PTSD) have a significant risk of developing type 2
diabetes. PTSD is an adjustment disorder after
experiencing a trauma and leads to massive stress
symptoms. An association between stress due to
mental illness and diabetes has been discussed
for a long time. Now for the first time, Karoline
Lukaschek of the Institute of Epidemiology II at
Helmholtz Zentrum München and Johannes Kruse
of the Clinic for Psychosomatic Medicine and
Psychotherapy of the University Hospital Giessen/
Marburg and colleagues have demonstrated a
clear association between the two diseases. The
scientists analyzed the data of the populationbased cohort study and administered a glucose
tolerance test. In the cohort, a total of 50 people
with PTSD were identified. 498 KORA participants
had manifest type 2 diabetes, and additionally
333 individuals showed signs of a pre-diabetic
metabolic state, a pre-form of diabetes. The
evaluation of the data revealed a significant
association of PTSD with type 2 diabetes; however, a higher incidence of pre-diabetes related
to psychological stress was not observed.
The scientists assume that the chronic stress
burden of PTSD patients leads to adjustments
in the hormonal reaction patterns. This can
have a pathological impact on the metabolism
and the utilization of glucose. Elucidating the
association between psychological factors and
metabolic disorders will therefore be an important task of diabetes research in the future.
According to the scientists, the treatment of
metabolic risk factors should already be part
of the therapy for patients with PTSD and other
mental illnesses.
Through meta-analyses with large numbers of individuals, 53 gene
loci that impact blood glucose levels were discovered or earlier
findings were confirmed; 10 gene loci associated with type 2 diabetes
were identified for the first time.
The presence of posttraumatic stress disorder is clearly associated
with the occurrence of type 2 diabetes. The cause is suspected to be
an activation of the hormonal stress axis through permanent stress
symptoms.
In genome-wide association studies (GWAS), state-ofthe-art analysis techniques are used to detect genetic differences
between healthy subjects and people with diseases such as diabetes
mellitus. Thus, associations between genetic alterations and
e xternal characteristics can be detected, and genetic risk factors
for the development and/or course of the disease can be identified.
Posttraumatic stress disorder (PTSD) is a mental illness which
is preceded by stressful events that are exceptionally threatening or
catastrophic (trauma). The event must not necessarily relate to one’s
own person but can also be experienced with others – for example as
witness to an accident or an act of violence.
BRIEF PROFILE
PROF. DR. DR.
KARL-HEINZ LADWIG
Leader of research group
Mental Health, Institute of
Epidemiology II, Helmholtz
Zentrum München
2009: Hans Roemer Award of
the DGPM (German Association
of Psychosomatic Medicine)
and DKPM (German College of
Psychosomatic Medicine)
since 2003: Professor of Psychosomatic and Psychological
Medicine at Technische
since 2002: Scientist at the
1990–2002: Head of GSF Clinical
Research Group, Klinikum
rechts der Isar, Technische
since 1998: Head of the
Psycho-Physiological
Laboratory at the German
Heart Center Munich
1996: Habilitation
1984: PhD, Technische
Unversität München
Karoline Lukaschek et al.:
Relationship Between Posttraumatic Stress Disorder and Type
2 Diabetes in a PopulationBased Cross-Sectional Study
with 2970 Participants. Journal
of Psychosomatic Research 74
(2013) 340-345 | doi: 10.1016/j.
jpsychores.2012.12.011
Karoline Lukaschek, Jens
Baumert, Rebecca Thwing
Emeny, Maria Elena Lacruz,
Cornelia Huth, Barbara
Thorand, Christine Meisinger –
Institute of Epidemiology II
Rolf Holle – Institute of Health
Economics and Health Care
Management
64 Senior scientist Gestational
Diabetes/ Type 2 Diabetes –
Pathogenesis and Prevention,
Institute of Diabetes Research,
2011: Ernst Friedrich Pfeiffer
Award of the German Diabetes
Society
2006: Research award of the
German Society for Nutritional
Medicine
2003: Science Prize, Association
of Nutritional Scientists
2003: Research Fellowship,
Instituto San Raffaele, Milan,
Italy
Since 2002: Scientific staff
member, Institute of Diabetes
Research, Helmholtz Zentrum
München and Technische
2002: PhD degree
Anette-Gabriele Ziegler et al.:
Long-Term Protective Effect of
Lactation on the Development
of Type 2 Diabetes in Women
with Recent Gestational
Diabetes Mellitus. Diabetes 61
(2012) 3167-3171 | doi: 10.2337/
db12-0393
Anette-Gabriele Ziegler, Maike
Wallner, Michaela Rossbauer,
Minna H. Harsunen, Christiane
Winkler – Institute of Diabetes
Research
Breastfeeding Reduces
Risk of Type 2 Diabetes
Breastfeeding is healthy – this is true not
only for the baby, but apparently also for the
mother. If she develops gestational diabetes
during pregnancy, she can reduce her risk of
developing type 2 diabetes by about 40 percent
through breastfeeding. Gestational diabetes
is a metabolic disorder limited to pregnancy
that increases the risk of developing type 2
diabetes after delivery. Impaired insulin release
and reduced insulin sensitivity result in this
metabolic disorder characterized by elevated
blood glucose levels. Women who had to be
treated with insulin during pregnancy bear the
greatest type 2 diabetes risk: Almost two thirds
of this group of participants of a gestational
diabetes study developed type 2 diabetes within
three years after delivery; within 15 years
even more than 90 percent developed type 2
diabetes postpartum. Previous studies reported
a short-term positive effect of breastfeeding on
the metabolism of the mother. These studies
indicate that breastfeeding for one to three
months improves lipid and glucose metabolism and reduces estrogen levels during that
time. Apparently even three years after birth,
breastfeeding influences the concentration of
two hormones that control hunger and satiety:
the appetite-stimulating hormone ghrelin and
the hormone PYY, which mediates a feeling of
satiety. The novelty of this study presented here
is the finding that breastfeeding prevents type 2
diabetes in the mother even over the long term.
According to the findings of the Institute of Diabetes Research, the duration of breastfeeding is
crucial: Only those who breastfed for more than
three months had a 15-year risk of 42 percent
of developing type 2 diabetes compared to 72
percent in mothers who breastfed less than 3
months. The test subjects were able to reduce
their diabetes risk even more if they fed their
baby during this period exclusively with breast
milk (15-year risk of 34.8 percent). By breastfeeding, the participants were able to delay the
development of type 2 diabetes by an average
of ten years. Now the aim of the research group
led by Anette-Gabriele Ziegler is to investigate
the mechanisms that are responsible for this
long-term effect of breastfeeding.
Women with gestational diabetes who breastfeed their baby have a
40 percent reduced risk of developing type 2 diabetes over the long
term. Especially mothers who breastfeed longer than three months
benefit from this protective long-term effect.
Gestational diabetes (diabetes during pregnancy) increases the
mother’s risk of developing type 2 diabetes later on. One woman in
two develops type 2 diabetes within ten years after delivery, although
initially her blood glucose levels returned to normal after pregnancy.
In Germany gestational diabetes occurs in about four percent of all
pregnancies.
80
No breastfeeding
Incidence of type 2 diabetes after delivery in %
BRIEF PROFILE
DR. SANDRA HUMMEL
65 Breastfeeding
≤3 months
60
Breastfeeding
>3 months
40
20
0
0
3
6
9
12
15
Years after delivery
Cumulative incidence of a subsequent development of type 2 diabetes in women who had
gestational diabetes during pregnancy: Subjects who breastfed longer than three months
had a significantly reduced risk of developing the disease.
66 BRIEF PROFILE
DR. JOACHIM HEINRICH
Acting director, Institute of
Epidemiology I, Helmholtz
Zentrum München
1997–2011: Deputy director,
Institute of Epidemiology
since 1992: Research group
leader Environmental
Epidemiology
1990–1992: Epidemiologist,
University of Wuppertal
1974–1989: Scientific assistant
and research group leader
Biostatistics, Erfurt Medical
School
Elisabeth Thiering et al.:
Long-Term Exposure to TrafficRelated Air Pollution and
Insulin Resistance in Children.
Results from the GINIplus and
LISAplus Birth Cohorts. Diabetologia 56 (2013) 1696-1704 |
doi: 10.1007/s00125-013-2925-x
Elisabeth Thiering, – Institute
of Epidemiology I
Josef Cyrys, Christa Meisinger –
67 Air Pollution Promotes
Insulin Resistance
Airborne pollutants play an important role
in the development of chronic diseases of the
respiratory and cardiovascular systems; for
diabetes, however, no reliable data has been
available until now. Elisabeth Thiering and
Joachim Heinrich of the Institute of Epidemiol
ogy I conducted a study on children to determine a possible association of air pollution and
insulin resistance, a precursor of type 2 diabetes.
They evaluated blood samples and data from
397 10-year-old children of a prospective cohort
study. For all residential addresses of the children since their birth, the respective trafficrelated air pollutant concentrations of particu
late matter and nitrogen dioxide (NO2) were
modeled and related to insulin resistance at the
age of ten years. The socio-economic status of
the families, the children’s exposure to passive
smoking and their birth weight, developmental
status and body mass index (BMI) were taken
into account. The statistical analyses revealed
that levels of insulin resistance were greater in
children with higher exposure to particulate air
pollution and nitrogen dioxide. Per 10.6 μg/m3
additional NO2 content in the air, the incidence
of insulin resistance increased by 17 percent.
Also the distance of the residence to roads
with heavy traffic was significant: Near to busy
roads the insulin resistance increased by seven
percent per 500 meters. These relationships
were independent of confounding factors such
as socioeconomic status, passive smoking,
or BMI. Air pollutants are potential oxidants
and can oxidize lipids and proteins directly
or activate oxidizing signaling pathways. This
oxidative stress may be an explanation for
the development of insulin resistance due to
traffic-related air pollutants. In the follow-up
observation of the cohorts, the researchers are
now investigating whether their observations
also apply to older children and whether e.g.
a change of residence with altered particulate
pollution allows conclusions about the significance of exposure in early childhood and then
later on. Currently, the clinical relevance of an
increased risk of insulin resistance caused by
particulate matter cannot be assessed. How
ever, the results support the hypothesis that the
development of diabetes in adulthood is related
to environmental factors earlier in life.
Increased particulate air pollution increases children’s risk of developing a resistance to insulin. This insulin resistance is the precursor
of type 2 diabetes.
The insulin resistance syndrome – also known as the metabolic
syndrome – refers to the common occurrence of several symptoms or
diseases: obesity, elevated fasting blood glucose and blood lipid levels
and high blood pressure. This so-called deadly quartet increases the
risk of atherosclerosis, diabetes and heart disease.
Type 1 Diabetes
Is Predicted by
Autoantibodies
The autoimmune disease type 1 diabetes often
manifests during childhood and adolescence.
Characteristic markers of the disease are
autoantibodies – i.e. immunoglobulins directed
against the body’s own components. They
appear when insulin producing cells in the
pancreas are destroyed and may be present in
the young patient's blood already at the age of
six months to three years. In a 20-year period
after the first appearance of so-called multiple
autoantibodies – sooner or later depending
on the presence of certain risk factors – the
disease manifests. In order to determine the
progression rate more precisely, scientists from
the Institute of Diabetes Research compared
the data from their own studies (BABYDIET and
BABYDIAB) with the data of two other prospective cohort studies (DAISY from Colorado and
DIPP from Finland). Overall, they were able
to analyze the results of 13 377 children over
a period of 20 years, making this study the
largest of its kind in the world. Anette-Gabriele
Ziegler and Christiane Winkler of the Institute
of Diabetes Research and their colleagues from
international cooperative projects found that
70 percent of children who have more than
one type of autoantibodies against islet cells
in the pancreas develop type 1 diabetes within
ten years. Over a period of 15 or 20 years, the
percentage of children is even 85 percent or
almost 100 percent. Subjects with only one type
of autoantibodies, however, develop type 1
diabetes only in 15 percent of the cases within
ten years, and children without autoantibodies
almost never develop type 1 diabetes.
These results show that the development of
type 1 diabetes is usually predictable. Therefore, the detection of autoantibodies provides
a relatively simple and cost-efficient way to
diagnose type 1 diabetes at an early stage and,
if applicable, in time to begin preventive and
therapeutic measures.
In type 1 diabetes, characteristic autoantibodies against islet cell
antigens often appear quite early in the blood of young patients.
T hrough the detection of multiple autoantibodies, the disease can
often be diagnosed in the preclinical stage.
Islet cell autoantibodies directed against different components
of the insulin-producing beta cells of the pancreas are characteristic
markers for type 1 diabetes. Due to the autoimmune process, the body
is no longer sufficiently supplied with insulin; if the destruction of
the beta cells exceeds a certain threshold, the disease manifests and
blood glucose levels rise.
BRIEF PROFILE
PROF. DR. ANETTE-GABRIELE
ZIEGLER
Director of the Institute of
Diabetes Research at Helmholtz
Zentrum München, Chair
of Diabetes and Gestational
Diabetes at Technische
2009–2013: Member of the
board of the German Diabetes
Association
2007–2009: Director of Department of Endocrinology and
Diabetes, Klinikum Schwabing,
Germany
Association
1996: Senior Clinician of the 3rd
Medical Department, Academic
Hospital Schwabing
1994: Dr. Bürger Büsing Award
of the German Diabetes Union
1993–1996: Heisenberg Fellow
of the German Research
Foundation at the Institute of
Diabetes Research in Munich
1992: Habilitation
1991: Specialization (Board) in
Internal Medicine
BRIEF PROFILE
DR. CHRISTIANE WINKLER
Research group leader of
Type 1 Diabetes Cohorts at the
Institute of Diabetes Research,
since 2012: Ernst Friedrich
Pfeiffer Award of the German
Diabetes Association
2009: Fellowship at the Pediatric
Epidemiology Center, University
of South Florida, Tampa, USA
since 2008: Post Doc
Forschergruppe Diabetes
e.V. (from 2010 on Institute of
Diabetes Research, Helmholtz
Zentrum München)
2008: PhD degree
Anette-Gabriele Ziegler et al.:
Seroconversion to Multiple
Islet Autoantibodies and Risk of
Progression to Diabetes in
Children.
Journal of the American
Medical Association (JAMA) 309
(2013) 2473-2479 | doi: 10.1001/
jama.2013.6285.
68 BRIEF PROFILE
PD DR. PETER ACHENBACH
Deputy director of the Institute
of Diabetes Research,
2013: Habilitation
Association
since 2008: Project leader
in the competence network
Diabetes mellitus and head
of the Islet Autoantibody
Standardization Program
since 2007: Member of the
research group Diabetes of TU
München
2005–2010: Early Career PatientOriented Diabetes Research
Award of the Juvenile Diabetes
Research Foundation (JDRF/
USA)
member at the Institute of
Diabetes Research Munich of
the Research Group Diabetes
e.V. and physician at the
Municipal Hospital MünchenSchwabing (until 2007)
Barbara Davis Center for
Childhood Diabetes, University
of Colorado, USA
Peter Achenbach et al.:
Characteristics of Rapid vs Slow
Progression to Type 1 Diabetes
in Multiple Islet AutoantibodyPositive Children. Diabetologia
56 (2013) 1615-1622 | doi:
10.1007/s00125-013-2896-y
Daniela Höfelmann, AnetteGabriele Ziegler – Institute
of Diabetes Research
69 Progression of
Type 1 Diabetes
Infections Increase
Type 1 Diabetes Risk
Type 1 diabetes is an autoimmune disease. Just
how quickly the autoimmune process progresses and type 1 diabetes develops appears to
be dependent on an interplay of genetic and
environmental factors. Scientists of the Institute
of Diabetes Research have partly succeeded in
elucidating relevant gene combinations.
The researchers led by Peter Achenbach and
Anette-Gabriele Ziegler analyzed data of the
BABYDIAB study. This prospective cohort study
includes participants from birth on who have
at least one relative with type 1 diabetes. Two
extreme groups were compared with each
other over an observation period of 20 years:
the group of slow progressors – children who
developed type 1 diabetes at the earliest ten
years after the first appearance of autoantibodies
– and the group of rapid progressors – children
who developed the disease at the latest three
years after their first appearance.
Basically, as far as demographic factors were
concerned, the children were comparable. With
respect to environmental factors they differed
Islet autoimmunity refers to the presence of
autoantibodies against insulin-producing beta
cells of the pancreas. It is characteristic of
type 1 diabetes and most commonly appears
between the ages of six months to three years.
Scientists at the Institute of Diabetes Research
have investigated whether in this phase of life
infectious agents might be considered a potential trigger for the dysregulation of the immune
system. They analyzed the data of children of
the BABYDIET study who have relatives with
type 1 diabetes and thus an increased risk for
islet autoimmunity. The parents kept a log of
the infections occurring in the first three years
of life of the children – differentiated according
to respiratory tract, gastrointestinal tract and
other infections. Fever and medication were
also recorded and the blood of the children was
regularly analyzed for autoantibodies.
In the first year of life an association between
respiratory infections and the presence of islet
autoantibodies was observed – especially with
only in the factors spontaneous delivery or
cesarean section. While half of the rapid progressors were delivered by cesarean section,
this was the case with only every sixth slow
progressor. The greatest immunological difference was seen in the development of autoantibodies against insulinoma-associated antigen-2
(IA-2A), which in general indicate a high
diabetes risk: The slow progressors showed a
delayed development of IA-2A. Characteristic of
the rapid progressors was a higher percentage
of risk variants of genes involved in immune
regulation. These gene variants are individually
connected to a relatively small increased risk of
disease. However, if they occur in certain combinations, this seems to favor an early onset of
the disease. This is especially true for genes
encoding for interleukin-2 (IL2), the alpha subunit
of the IL-2 receptor (CD25), interleukin-10 and
interferon-induced IFIH1 helicase. In contrast,
no difference could be found regarding the HLA
(human leucocyte antigen) gene variants that
pose the greatest risk for type 1 diabetes.
infections of the upper respiratory tract such as
nasopharyngitis (the common cold). Children
with islet autoantibodies were infected at least
twice in the first year, mainly with pathogens
of the respiratory tract. Children who had more
than five respiratory infections in the first year
had the highest risk of islet autoimmunity. The
scientists suspect, however, that the increase
in autoimmune risk is not caused by a specific
virus but rather by the sum of infections and
the thus released inflammatory cytokines.
According to the principal investigator of the
study, Anette-Gabriele Ziegler, and her colleagues, frequent respiratory infections in the
first year of life represent a possible risk factor
for type 1 diabetes. In genetically disposed risk
children, multiple episodes of colds in early
childhood should be avoided if at all possible,
and vaccinations or anti-inflammatory therapies
should be taken into consideration as preventive
measures against type 1 diabetes.
The development of type 1 diabetes may take only a few months,
but also many years. A combination of specific risk gene variants,
the early appearance of autoantibodies against the insulinoma-
associated antigen-2 (IA-2A) and a birth by cesarean section seem
to facilitate a rapid progression of the autoimmune disease.
Infections in the first months of life predispose to the later presence
of autoantibodies, which are responsible for the development of type
1 diabetes. In particular, respiratory diseases in the first year of life,
especially an acute common cold (nasopharyngitis) appear to play
an important role.
Type 1 diabetes is the most common metabolic disease in
childhood and adolescence. The body’s immune system attacks the
insulin-producing cells in the pancreas and destroys them. This
autoimmunity, which underlies the metabolic disorder, is based on
a genetic predisposition and is influenced by environmental factors.
Type 1 diabetes can occur at any age. The peak incidence is during
puberty from age 10 to 15 years.
In islet autoimmunity the immune system is mistakenly directed
against endogenous components, namely against various proteins
of the insulin-producing beta cells of the pancreas. These cells are
gradually destroyed and insulin production is stopped – the outcome
is the development of type 1 diabetes.
BRIEF PROFILE
DR. ANDREAS BEYERLEIN
Epidemiology at the Institute of
Zentrum München
2012: Postdoc, Technische
2011-2012: Consultant, Bavarian
State Office of Statistics
since 2011: PhD degree, LudwigMaximilians-Universität
München
Andreas Beyerlein et al.:
Respiratory Infections in Early
Life and the Development of
Islet Autoimmunity in Children
at Increased Type 1 Diabetes
Risk. JAMA Pediatrics 167
(2013) 800-807 | doi: 10.1001/
jamapediatrics.2013.158
Fabienne Wehweck, Maren
Pflueger, Anette-Gabriele
Ziegler – Institute of Diabetes
Research
70 BRIEF PROFILE
DR. STEFANIE EYERICH
group T Cell Biology in Health
and Disease at the Center of
Allergy and Environment
(ZAUM)/ Institute of Allergy
Research, Technische
Universität and Helmholtz
Zentrum München
2013: Robert Koch Postdoctoral
Award for Immunology,
ACTERIA Early Career Research
Prize for Allergology
2012: Dr. Ernst Wiethoff Award
2011: Egon Macher Award of
the Association of Dermatology
Research
2010-2012: Assistant to the
group leader, Center of Allergy
and Environment
2009-2010: Postdoc, Center of
Allergy and Environment
2008-2009: Postdoc, National
Heart and Lung Institute (NHLI),
Department of Allergy and
Clinical Immunology, Imperial
College London, UK
2008: PhD degree
Davide Pennino et al.: IL-22
Suppresses IFN-ɣ–Mediated
Lung Inflammation in
Asthmatic Patients.
Clin Immunol. 131 (2013) 562-70
| doi: 10.1016/j.jaci.2012.09.036.
Epub 2012 Nov 19.
Further Authors from
Carsten B. Schmidt-Weber –
Institute of Allergy Research
Davide Pennino, Renate Effner,
Maria Quaranta, Viviana
Marzaioli, Liliana Cifuentes –
Center for Allergy and
Environment
71 Interplay of
Cytokines in Asthma
More Risk Genes
for Allergies
The cytokine interleukin-22 may control the
extent of asthmatic lung inflammation, according
to a study by an international research team. The
analysis of T-helper cells derived from the lungs
of patients with asthma detected the presence of
the T-helper cell type Th22, which was originally
described in the skin. Interestingly, however, the
lead cytokine of the Th22 cells, interleukin (IL)-22,
was co-produced in a number of T cells with
gamma interferon (IFN- ). IFN- is considered
to be pro-inflammatory because, among other
things, it stimulates the production of adhesion
molecules in epithelial cells, while interleukin-22
has the opposite effect – it promotes defense
mechanisms and wound healing. In an in vitro
model using human bronchial epithelial cells,
the researchers examined the interaction of the
two substances and demonstrated that IL-22
In a meta-analysis of several genome studies an
international team of scientists has identified ten
genes that are involved in the development of
allergic sensitization. In the genome-wide association studies (GWAS), the scientists correlated
the genetic profile of the study participants with
the presence of specific IgE antibodies. They
discovered that ten loci are involved in a total
of 25 percent of all allergic sensitizations, the
immunological process in which antibodies form
against allergens, which are actually harmless
substances in the environment. These antigens
subsequently cause the allergic symptoms.
The researchers analyzed data from more than
10 000 people with allergic sensitization and
approximately 20 000 control subjects. Among
them were participants of the German birth
cohorts GINIplus and LISAplus; their evaluation
was carried out by Marie Standl and Joachim
and IFN- are apparently antagonists. In the
presence of IFN- , IL-22 cannot fully develop its
positive characteristics, and this leads to diminished wound healing responses. On the other
hand, however, IL-22 also suppresses the pro-inflammatory effect of IFN- in the inflammatory
process. The results suggest that the therapeutic
administration of interleukin-22 or measures that
support its production could reduce the acute
inflammatory response in asthma. However, this
protein is ambivalent in its effect. Too much IL-22
can lead to excessive proliferation of epithelial
cells, a phenomenon that is e.g. observed in psoriasis. In addition, IL-22 interacts strongly with
other interleukins, and these interactions are
not yet sufficiently understood. As next step the
scientists therefore want to study the interaction
of IL-22 and IFN- in the mouse model.
Heinrich of the Institute of Epidemiology I. This
comprehensive genetic analysis in relation to the
objective measurement of allergic sensitization
enables an assessment of the identified genes
as risk factors for allergic diseases. In addition,
all of these genes showed a correlation with
the occurrence of allergic manifestations such
as hay fever and asthma. The results of this
meta-analysis indicate that enormous genetic
diversity underlies allergic diseases. Further
more, lifestyle factors and environmental
stresses play an important role in future allergy
research and the treatment of patients. Now,
based on the genetic information, the scientists
want to investigate the involved molecular
mechanisms in more detail in order to obtain
new insights into the pathomechanisms of allergies and other immune diseases.
Scientists at the Center of Allergy and Environment (ZAUM) of
Helmholtz Zentrum München and Technische Universität München
investigated the anti-inflammatory role of interferon-22 in allergic
asthma in the framework of an international research group.
In a meta-analysis of several genome studies, an international research
team which included scientists of the Institute of Epidemiology I has
identified 10 genes that together are responsible for the development of
allergic sensitization.
Both interleukins (IL-x) and interferons belong to the family
of cytokines. They are endogenous tissue hormones, which act as
communication factors between immune and tissue cells.
Allergic diseases are increasing throughout the world. In Europe
alone an estimated 80 million people are affected. The reason for the
allergic reaction is a complex gene-environment interaction.
BRIEF PROFILE
DR. JOACHIM HEINRICH
Acting director of the Institute
of Epidemiology I of Helmholtz
Zentrum München
1997–2011: Deputy
director of the Institute of
Epidemiology of Helmholtz
Zentrum München
since 1992: Leader of the
research group Environmental
Epidemiology
1990–1992: Epidemiologist,
University of Wuppertal
1974–1989: Scientific assistant
and leader of the research
group Biostatistics Erfurt
Medical School
Klaus Bønnelykke et al.:
Meta-Analysis of Genome-Wide
Association Studies Identifies
Ten Loci Influencing Allergic
Sensitization. Nature
Genetics 45 (2013) 902-906 |
doi: 10.1038/ng.2694
Marie Standl, Carla Tiesler,
Elisabeth Thiering,
Institute of Epidemiology I
Katharina Schramm, Institute of
Human Genetics
Melanie Waldenberger,
Epidemiology
BRIEF PROFILE
PROF. DR. ROLF HOLLE
Economic Evaluation,
Institute of Health Economics
and Healthcare Management,
Since 2005: Adjunct professor
at the Medical Faculty of
Ludwig-MaximiliansUniversität München
1995: Habilitation, University
of Heidelberg
1990: Dr. biol. hom., Medical
Faculty, University of Giessen
member at the University of
Giessen and the University of
Heidelberg
Petra Menn et al.: Direct
Medical Costs of COPD – An
Excess Cost Approach Based on
Two Population-Based Studies.
Respiratory Medicine 106
(2012) 540-548 | doi: 10.1016/j.
rmed.2011.10.013
Petra Menn, Jürgen John –
Institute of Health Economics
and Healthcare Management
Joachim Heinrich, Stefan
Karrasch, Holger Schulz –
Institute of Epidemiology I and
Comprehensive Pneumology
Center Munich (CPC)
Annette Peters – Institute of
Epidemiology II
73 Cost of Medical Care in
Early Stages of COPD
Scientists of the Institute of Health Economics
and Health Care Management at Helmholtz
Zentrum München have investigated the associ
ation between early stages of COPD and the
utilization of medical care. The researchers based
their investigation on the KORA study comprising
more than 2000 participants between 40 and
90 years of age. The aim of the study was to
determine whether already in the early stages
of COPD there are excess costs for medical care.
COPD is commonly known as smoker’s cough;
the official name is chronic obstructive pulmonary disease. The disease is incurable; it is only
possible to slow its progression. An estimated
13 percent of adults in Germany over 40 years
of age suffer from this disease, whereby in the
early stages it usually remains undiagnosed.
The researchers calculated the costs per
year incurred by visits to the doctor, hospital
stays and medications for these individuals.
By means of a pulmonary function test they
identified test subjects with reduced lung
function and classified them into mild (Stage I)
or moderate (Stage II) COPD. In computerassisted interviews using detailed question
naires, participants were asked about their visits
to the doctor, hospital stays and medications.
From this data, their costs for medical care
were derived. Then the researchers compared
the calculated costs between participants with
and without COPD taking age, sex and level of
education into account. The results show that
people with early stage (I) COPD do not cause
substantially higher costs for medical treatment
than participants without the disease.
However, as soon as the moderate stage is
reached, costs increase and are on average
990 euros higher per year for people with COPD
compared to people with normal lung function.
In view of the high incidence of COPD, this means
that alone for the treatment of this stage, annual
costs of about two billion euros are incurred
for the German health care system. The total
costs of COPD are many times higher, especially
when patients in stages III and IV are included
in the cost calculation. In order to quantify these
costs as well, the research group collaborates
within the Competence Network COPD, where
information from 2700 patients across Germany is
being collected and analyzed. So far, from these
results, the researchers conclude that suitable
preventive measures are needed for COPD not
only from a medical perspective but also from an
economic perspective to keep the disease from
progressing to a more advanced stage. First and
foremost, this means that smokers who already
suffer from mild COPD should be motivated to
stop smoking, since smoking cessation is one
of the most effective interventions to slow the
worsening of the disease.
Health care utilization
72 5
No COPD
Stage I
4
Stage II
3
2
Adjusted
total costs per year
in euros
1
No COPD Stage I
Stage II 0
Number of outpatient visits
(3-month period)
Days in hospital
(12-month period)
Number of medications
(7 days)
Comparison of the frequency of outpatient visits, hospital stays and use of medication between
healthy individuals and subjects with COPD in the mild stage (I) or moderate stage (II). The resulting
costs were estimated, taking into account age, sex and level of education.
People who suffer from a moderate form of COPD cause around 990
euros higher medical costs due to illness per year than comparable
individuals who do not have the disease. For the treatment of this
disease stage alone, this means annual costs of about two billion euros
for the German healthcare system. Therefore preventive measures
are needed to stop the development and progression of COPD.
COPD stands for chronic obstructive pulmonary disease;
It is caused by a chronic inflammatory pulmonary disorder that leads
to the narrowing of the small airways. It occurs primarily in smokers
and is often accompanied by coughing, excessive mucus production
and breathlessness.
1822
1830 (+0 %)
2812 (+54 %)
74 BRIEF PROFILE
DR. JOVICA NINKOVIC
Scientist at the Institute of
Stem Cell Research, Helmholtz
Zentrum München
2010: Scopus Neuroscience
Award
2005–2007: Postdoc, Institute of
Stem Cell Research
75 Key to Neurogenesis
The formation of nerve cells is mainly restricted in mammals to the development phase and
takes place in the adult stage only in a few
regions of the forebrain. The usual case in
the adult brain is the formation of supporting
cells, also called glial cells. In fact, even stem
cells that were transplanted as a therapy for
neurodegenerative diseases usually develop
into glial cells instead of the desired neurons.
The few regions of adult neurogenesis offer an
opportunity to investigate just how neurons
can be formed even in the adult brain. Both
in the developing brain and in the adult brain
numerous transcription factors are involved in
neurogenesis. However, it is still unclear how
the final differentiation of the progenitor cells is
controlled at the molecular level.
One key mechanism in this process was elucidated by the team led by Jovica Ninkovic and
Magdalena Götz of the Institute of Stem Cell Research. By searching for the interaction partners
of the transcription factor Pax6, which plays
a major role both in the development of the
brain and in adult neurogenesis, the scientists
showed that Pax6 interacts with the so-called
BAF complex, which can alter the chromatin
structure, and that this interaction determines
the fate of the neural progenitor cells. Through
the interaction, the chromatin is modified in
such a way that certain genes that serve the
regulation of neuronal differentiation become
accessible. As a result, the genes necessary
for neuronal differentiation are more strongly
expressed and the fates of neuronal cells – even
in surroundings where otherwise only glial cells
are formed – are stabilized. A loss of function of
Pax6 or BAF – depending on the surroundings –
leads to the formation of glial cells instead of
neurons. Thus, the scientists describe for the first
time certain molecular prerequisites of neurogenesis in the adult brain. This could be the basis for
new therapies, e.g. to stimulate the formation of
nerve cells in neurodegenerative diseases or after
brain injuries and to replace damaged cells.
Jovica Ninkovic et al.: The BAF
Complex Interacts with Pax6
in Adult Neural Progenitors
to Establish a Neurogenic
Cross-Regulatory Transcriptional
Network. Cell Stem Cell 13
(2013) 403-418 | doi: 10.1016/j.
stem.2013.07.002
Neural progenitor cells can differentiate into different cell types
in the adult brain: into new neurons, but also into glial cells. In
the study, it was shown that the transcription factor Pax6 causes a
change in chromatin structure by interacting with the so-called BAF
complex and thereby influences the fate of neural progenitor cells.
Andrea Steiner-Mezzadri,
Giacomo Masserdotti, Stefania
Petricca, Judith Fischer,
Magdalena Götz – Institute of
Stem Cell Research
Johannes Beckers, Martin Irmler,
Chichung D. Lie – Institute
of Experimental Genetics
A nerve cell or neuron is a cell that is specialized in signal
t ransduction and synaptic transmission. Neurons are found in
almost all multicellular animals. All of the nerve cells of an
organism and the glial cells comprise the nervous system.
Pax6
BAF
Transcription
factors
Pou3f4
Nfib
Sox11
Diagram showing the interaction of transcription factors that decide
the fate of neuronal progenitor cells.
Transcription-relevant
BAF complex
76 BRIEF PROFILE
DR. LEDA DIMOU
Scientific staff member of the
Institute of Stem Cell Research,
and Institute of Physiological
Genomics at Ludwig-
Maximilians-Universität
München
since 2011: Leader of a
research group at the Institute
of Physiological Genomics at
and guest scientist at
2003–2006: Postdoc in the
Institute of Brain Research of
the University of Zurich
1998–2002: PhD at the
University of Heidelberg and at
the Max Planck Institute
of E xperimental Medicine,
Göttingen
until 1998: Study of Biology
at the University of Heidelberg
77 Oligodendrocytes and
Multiple Sclerosis
Oligodendrocytes are cells of the central nervous system that produce the myelin sheath, a
lipidous biomembrane which coats the axons
of nerve cells to provide insulation that allows
electrical signals to propagate more efficiently.
This insulation is necessary in order to ensure
a rapid nerve conduction velocity.
In some neurological diseases and in particular
in multiple sclerosis, the immune system
destroys the myelin. As recent studies have
shown, depending on their location in the brain,
oligodendrocytes can regenerate throughout life
from oligodendrocyte progenitor cells. The team
led by Leda Dimou has now taken a closer look
at these oligodendrocyte progenitor cells to
identify the reason for these differences in their
differentiation potential.
Depending on the brain region in which the
progenitor cells are located, a smaller or greater
quantity of oligodendrocytes is generated
which can produce myelin. Progenitor cells in
the white matter of the brain, which consists
primarily of nerve fibers, generate more
oligodendrocytes than those in the gray matter,
where the neuronal cell bodies are found. The
aim of the researchers of the Institute of Stem
Cell Research was to investigate whether
this difference is cell-intrinsic or whether it is
dependent on the local environment. In the
mouse model, through transplantation of the
progenitor cells, the researchers observed
how these develop independently from their
original surroundings. The result was that
the differences are primarily cell-intrinsic:
Progenitor cells from the white matter develop
in both brain regions into myelin-producing
oligodendrocytes. Progenitor cells from the
gray matter are less effective. The next step for
the researchers will be to identify the factors
which determine the effectiveness of these
oligodendrocyte progenitor cells. Their goal is
to define conditions in which these progenitors
will always differentiate into oligodendrocytes
that form myelin. Even though a therapy for
multiple sclerosis still appears to be far in the
distance, this research is an important contribution to understanding the origin and course
of such neurological diseases.
Oligodendrocytes are cells of the central nervous system that
enable nerve cells to efficiently conduct electrical signals. Scientists
of the Institute of Stem Cell Research have now gained new insights
into the origin and development of oligodendrocytes, which may
play an important role in multiple sclerosis.
Francesca Viganò et al.: Transplantation Reveals Regional
Differences in Oligodendrocyte
Differentiation in the Adult
Brain. Nature Neuroscience
(2013) | doi: 10.1038/nn.3503
Francesca Viganò, Magdalena
Götz – Institute of Stem Cell
Research
Multiple Sclerosis (MS) is a chronic inflammatory disease of the
central nervous system and is caused by demyelination of the nerves
in which the body’s own immune cells attack the myelin sheaths
of the nerve axons. The cause of this autoimmune reaction is not
yet fully understood. MS is one of the most common neurological
diseases in young adults. To date, no cure has been found.
Faster Production
of Disease Models
An efficient method for the rapid production
of mouse disease models has been developed
at Helmholtz Zentrum München. Mouse models
are used for the genetic analysis of disease
mechanisms and are still considered to be
indispensable for this purpose. In most cases,
models are used which are produced
by targeted mutations in embryonic stem cells
(ES cells). However, this production process
is complex and time-consuming, since among
other steps, targeting vectors must be constructed with selection markers, mutated ES
cells must be isolated and germline chimeras
must be produced. All of these procedures are
very laborious and time intensive. Including
all steps, the scientists often need one to two
years to produce a knockout mouse model
using these methods. This poses a hurdle for
the analysis of the ever-increasing number of
known human disease-associated mutations
that are discovered using high-throughput
analyses of the human genome.
Scientists of the Institute of Developmental
Genetics have succeeded in developing a faster
way to produce mouse disease models. By
microinjection of so-called TALENs (Transcription
Activator-like Effector Nucleases) and synthetic
oligodesoxynucleotides directly into the embryos
in the one-cell stage, any desired mutation or
deletion can be induced within two days and can
also be reversed. Since for this purpose neither
ES cultures nor targeting vectors are required,
this technology enables immediate changes in
the germ cells, so that heterozygous mutants are
available within 18 weeks. This novel method is
thus significantly faster than the previously used
methods. Through the intelligent production of
mouse models required for drug development,
the number of experimental animals needed for
this purpose can be drastically reduced.
BRIEF PROFILE
PROF. DR. WOLFGANG WURST
Developmental Genetics,
Helmholtz Zentrum München,
chair of Developmental Genetics,
Technische Universität München
1994–1997: Junior group leader
member, Samel Lunenfeld
Research Institute of the Mount
Sinai Hospital, Toronto, Canada
1988–1989: Postdoc, University
of Göttingen
BRIEF PROFILE
PROF. DR. MARTIN
HRABE DE ANGELIS
Director and chair of the
Institutes of Experimental
Genetics, Helmholtz Zentrum
München and Technische
Universität München, member
of the board of the German
Center for Diabetes Research
1997–2000: Leader of the
research group Functional
Genetics
1994–1997: Postdoc, The Jackson
Laboratory, Maine, USA
BRIEF PROFILE
DR. RALF KÜHN
Scientific team leader, Institute
of Developmental Genetics,
By microinjection of TALENs and synthetic oligodesoxynucleotides,
the scientists altered the genes in the fertilized egg cells of mice so
that all progeny cells were equipped with the same mutation. Because
through this method the laborious steps to produce targeted mutants
are not required, animal models can be established much faster and
using substantially fewer experimental animals.
TALENs – Transcription Activator-like Effector Nucleases
are modular enzymes that recognize and cleave specific double-
stranded DNA sequences. It is possible to create different sequence-
specific variants with which virtually all genes in the genome can
be cleaved and altered by co-administration of synthetic oligodeoxy
nucleotides. Thus, specific genes can be removed selectively, and
genetic defects can be incorporated into the cell or repaired.
1998–2002: Head of Mouse
Genetics, Artemis Pharmaceuticals
1994–1998: Postdoc and
scientific assistant,
University of Cologne
Benedikt Wefers et al.:
Direct Production of Mouse
Disease Models by Embryo
Microinjection of TALENs and
Oligodeoxynucleotides. Proc.
Natl. Acad. Sci. U.S.A. 110
(2013) 3782-3787 | doi: 10.1073/
pnas.1218721110
Benedikt Wefers, Melanie
Meyer, Oskar Ortiz, Jens
Hansen – Institute of
Developmental Genetics
78 79 Human Glial Cells Can
Be Reprogrammed
The regeneration of functional neurons is
an innovative approach to the therapy of
neurodegenerative diseases such as Alzheimer’s
disease or stroke. In the adult mammalian brain,
however, most areas no longer contain neuronal
stem cells or progenitor cells from which new
neurons could be formed. Several years ago,
members of the Institute of Stem Cell Research
headed by Magdalena Götz showed in a mouse
model that by selective transfer of individual
transcription factors it is possible to reprogram
glial cells – i.e. supporting cells with multiple
functions – to nerve cells. Transcription factors
are regulatory proteins that control which genes
are active or inactive in the cells. Now a research
team led by Magdalena Götz and Benedikt
Berninger has succeeded in proving that the
animal experimental approach is also applicable to
human glial cells. Using specimens derived from
Marisa Karow et al.: Reprogramming of Pericyte-Derived
Cells of the Adult Human Brain
into Induced Neuronal Cells.
Cell Stem Cell 11 (2012)
471-476 | doi: 10.1016/j.
stem.2012.07.007
Giacomo Masserdotti, Sergio
Gascón – Institute of Stem Cell
Research
Muhammad A. Khan,
D. Chichung Lie – Institute of
Developmental Genetics
the surgery of adult epilepsy patients, Marisa
Karow and her colleagues showed that specific
cells of the cerebral cortex (cells derived from
pericytes) can be reprogrammed into neurons
through the retrovirus-mediated expression of
the two transcription factors Sox2 and Mash1.
These induced neurons fire action potentials and
form networks with other neurons; thus, they
are able to integrate themselves into neuronal
networks. This shows for the first time that there
are cells in the adult brain which can be directly
reprogrammed into functional neurons for
therapy purposes – without having to take a
detour via pluripotent cells. On the basis of
this knowledge, researchers are seeking active
agents to activate the reprogramming of glial
cells in patients with neurodegenerative diseases
or brain traumas and thus to initiate a self-healing
process in the injured areas of the brain.
Trnp1 Regulates
Expansion of
Cerebral Cortex
Different brain regions have different tasks and
must be specifically expanded as required. In
the forebrain of mammals, the cerebral cortex –
which is responsible for cognitive function –
is usually highly folded and expanded. The
more folds and wrinkles there are, the larger
the surface and the better the brain can absorb
and process information. In humans, the brain
surface of the fetus is mostly smooth until
approximately the sixth month of pregnancy;
it is not until after this that the folding begins.
Until this study, it was completely unknown
which mechanisms trigger the expansion and
folding of the brain in the course of fetal development. Now for the first time, Magdalena Götz
and her team have identified the corresponding
molecular mechanism in the mouse model:
The responsible protein is the nuclear protein
Trnp1, whose dynamic regulation triggers an
enormous proliferation of neurons of the cerebral cortex and stimulates folding even in mice
that normally exhibit smooth, unfolded brains.
Trnp1 is thus a key protein for the expansion
and folding of the cerebral cortex. During fetal
development it is dynamically controlled: In the
early phases of development Trnp1 levels are
high. This favors the formation of radial glial
cells, and specific brain regions expand. Later,
Trnp1 levels drop again to lower levels. As a
consequence, the formation of various progenitor cells and glial cells is stimulated, and a particularly large number of newly formed neurons
arrange themselves in a folded structure.
This molecular mechanism is particularly
interesting because both the expansion and the
folding of the brain are regulated by the same
molecule – Trnp1. Thus, Trnp1 represents a very
promising approach for investigation of the
cellular and molecular mechanisms underlying
these complex processes – an approach that
Götz and her team want to pursue further.
For the first time the formation of new nerve cells from somatic
cells of the human brain has succeeded: Specific cells of the adult
human cerebral cortex could be reprogrammed into functioning
neurons with the aid of two transcription factors.
During the fetal development of many mammals the cerebral cortex
increases in size and becomes folded. Scientists of Helmholtz
Zentrum München have now succeeded in identifying the key protein
responsible for this process.
The brain consists of two main types of cells: the neurons, which
transmit information, and the glial cells, which have a supporting
function and are involved in the metabolism of the brain. In many
degenerative diseases of the brain – stroke, Alzheimer’s disease,
Parkinson’s disease – the neurons are primarily damaged.
The cerebral cortex is the neuron-rich outer layer of the
cerebrum. Depending on the region, it is only two to five m
illimeters
thick and is part of the gray matter of the cerebrum. The nerve
fibers of the neurons of the cerebral cortex extend below the cortex
and form the white matter of the cerebrum that consists largely of
myelinated nerve fibers bundled into tracts.
BRIEF PROFILE
PROF. DR. MAGDALENA GÖTZ
Director, Institute of Stem Cell
Research, Helmholtz Zentrum
München and chair of
Physiological Genomics at
2014: Ernst Schering Award
2013: ERC Advanced Investigator
Grant and Remedios Caro
Almela Prize
2010: Federal Cross of Merit
with ribbon
2008: Alzheimer Research Award
of the Hans and Ilse Breuer
Foundation
2007: Hansen Family Award
and Gottfried Wilhelm
Leibniz Prize of the German
Research Foundation
2000: Habilitation
1997–2003: Scientist
and research group leader at
Max Planck Institutes in
Göttingen and Munich
1992–1996: Postdoc in Tübingen,
London and Harlow
Ronny Stahl et al.: Trnp1 Regulates Expansion and Folding of
the Mammalian Cerebral Cortex
by Control of Radial Glial Fate.
Cell 153 (2013) 535-549 | doi:
10.1016/j.cell.2013.03.027
Ronny Stahl, Tessa Walcher,
Gregor Alexander Pilz, Silvia
Cappello –
Institute of Stem Cell Research
Martin Irmler, Johannes
Beckers – Institute of Experimental Genetics
80 Original Publication:
Katharina Vogel et al.: Roquin
Paralogs 1 and 2 Redundantly
Repress the Icos and Ox
40 Costimulator mRNAs and
Control Follicular Helper T
Cell Differentiation. Immunity
38 (2013) 1-14 | doi: 10.1016/j.
immuni.2012.12.004
Katharina Vogel, Stefanie Edelmann, Katharina M. Jeltsch,
Gitta A. Heinz, Sebastian C.
Warth, Kai P. Hoefig, Claudia
Lohs, Elisabeth Kremmer –
Institute of Molecular Immunology
Jessica Zöller, Mathias Heikenwälder – Institute of Virology
Frauke Neff – Institute of
Pathology
Joel Schick, Wolfgang Wurst –
Institute of Developmental
Genetics
Arie Geerlof – Institute of
Structural Biology
Roquin proteins control the activation and
differentiation of T cells by regulating their gene
expression at the level of messenger RNA. The
function of the RNA-binding proteins is first and
foremost to ensure immunological tolerance and
to prevent excessive immune reactions – such as
in autoimmune diseases.
Katharina Vogel and Stephanie Edelmann of
the Institute of Molecular Immunology showed
how the two proteins, Roquin-1 and Roquin-2
can replace each other functionally and which
consequences result from the combined loss of
both Roquin genes. In the case that the Roquin1san form is present in a single point mutation,
Roquin-1 inhibits the function of Roquin-2. In the
absence of Roquin-1, Roquin-2 takes over and
compensates for its function. The proteins are
consequently interchangeable in their molecular
function and fulfill a kind of reserve function for
each other. The loss of both Roquin genes leads
to an uncontrolled accumulation of effector T
cells and particularly of follicular helper T cells.
If these T cells then trigger an immune response
against the body’s own structures, a clinical
picture emerges that is very similar to lupus
erythematodes, an autoimmune disease that
attacks the skin and internal organs. A single
point mutation in the Roquin-1 gene, i.e. the
exchange of a single amino acid in the protein,
leads to such a disease. Interestingly, in this
case the Roquin-2-protein is unable to take over
the function of the defective Roquin-1, resulting
in a complete loss of the Roquin function. The
research team also identified the molecular
targets of the Roquin proteins, the Icos and
Ox40 costimulator mRNAs.
This research demonstrates that the Roquin-1
and 2 proteins are of great importance for
T cell differentiation in immune reactions.
In future studies, the focus will be on elucidating the regulation of these factors because
this regulation mechanism can be used as a
therapeutic target in the treatment of auto
immune diseases.
Roquin-1san
Roquin-2
Proteins
since 2012: Chair of
Systemic Immunology in the
Institute of Immunology at
2011: ERC Starting Grant
2009-2011: Research group
leader at the Institute of
Molecular Immunology
2001–2005: Postdoc at
Harvard Medical School,
Center for Blood Research
Max Delbrück Center for
Molecular Medicine
How Roquin Family
Proteins Control T Cells
1
Induce
degradation
Regulation of
mRNA expression
Head of the research unit
Molecular Immune Regulation
in the Institute of Molecular
Immunology, Helmholtz
Zentrum München
2
Icos
0x40
Roquin-1/-2
The two genetic variants Roquin-1 and Roquin-2 are important
components in the activation and differentiation of T cells. The
proteins encoded by them are interchangeable in their molecular
function, and defects in the Roquin-1 gene can cause a utoimmune
diseases. For the first time, scientists have now analyzed the
complex interaction of the two proteins and have examined their
activity as regulators of gene expression.
Lymphocytes
BRIEF PROFILE
PROF. DR. VIGO HEISSMEYER
81 3
CD4 T cell
Tfh cell differentiation
The proteins Roquin-1 and Roquin-2 repress the Icos and Ox40 costimulator mRNAs and regulate
the differentiation of T cells.
Autoimmunity is defined as the inability of an organism to
recognize its structural components as endogenous. This leads to
a pathological reaction of the immune system against endogenous
molecules or tissues which is manifested as an autoimmune disease.
The exact causes for the dysregulation are not yet known.
82 BRIEF PROFILE
DR. PHILIPP A. GREIF
Scientific staff member
of the Clinical Cooperation
Group “Pathogenesis of Acute
Myeloid Leukemia” at
since 2012: Junior research
group leader, German Cancer
Consortium (DKTK), partner
site Munich
2010: Merit Award International
Society of Oncology and
Biomarkers, Research Award
from the Anne Liese Gaebel
Foundation
since 2008: Resident physician,
Department of Internal Medicine
III, University Hospital of Munich
2005-2008: Postdoc, Clinical Cooperation Group “Pathogenesis
of Acute Myeloid Leukemia” at
2004–2005: Human Genetics
Programme, World Health
Organization (WHO), Geneva
Sabrina Opatz et al.: Exome
Sequencing Identifies Recurring
FLT3 N676K Mutations
in Core-Binding Factor
Leukemia. Blood 122 (2013)
1761-1769 | doi: 10.1182/
blood-2013-01-476473
Harald Polzer, Tobias Herold,
Sebastian Vosberg, Stefan K.
Bohlander, Karsten Spiekermann – Clinical cooperation
group Pathogenesis of
Acute Myeloid Leukemia
83 Personalized Leukemia
Therapy Appears
within Reach
Cancer is caused by mutations in the genome
due to different factors. The gene mutations
mostly affect the regulators of cellular metabolism or cell growth. As a consequence, the
cells undergo malignant transformation and
proliferate in an uncontrolled manner. Many
of such gene mutations have been identified in
leukemia.
In about one third of patients with acute myeloid leukemia (AML) the malignant cells have
a mutation in the growth-regulating receptor
FLT3. As the team of scientists headed by Dr.
Philipp Greif and Professor Karsten Spiekermann have now discovered by means of exome
sequencing, blood cancer cells from a substantial number of patients in a subgroup of
AML (so-called core-binding factor leukemias)
also carry mutations in this receptor. The gene
alterations at position N676 were previously
unknown and now allow a new classification of
this leukemia form, which is characterized by
a particularly high cell count. In addition,
according to the researchers, the newly identified
FLT3 receptor mutations in this leukemia group
provide a new target for personalized treatment
of the disease. Inhibitors of the FLT3 receptor
are already available and can now be administered to the affected patients.
The study was conducted by the clinical cooperation group “Pathogenesis of Acute Myeloid
Leukemia”, a joint institution of Helmholtz
Zentrum München and the Department of
Internal Medicine III at the University Hospital
of Munich. The aim of the clinical cooperation
group (CCG) is to identify leukemia-causing
mutations and to investigate why certain mutations
can cause leukemia. The head of the CCG Wolfgang
Hiddemann emphasizes the importance of this
interdisciplinary collaboration: The results show
in an exemplary way how innovative research
methods, such as high-throughput DNA
sequencing, allow discoveries, even in structures
that have already been thoroughly examined.
These insights into the molecular basis of
the disease open up new treatment options
for patients.
Specific mutations of the FLT3 receptor may contribute to the
development of acute myeloid leukemia. The Flt3 receptor regulates
cell growth; activating gene mutations promote uncontrolled proliferation of white blood cells. This finding of the clinical cooperation
group “Pathogenesis of Acute Myeloid Leukemia” can be used to
develop a therapy by means of specific inhibitors that inhibit the
growth signal.
Acute myeloid leukemia (AML) is the most common cancer of
the hematopoietic system occurring in adults. Only about 25 to 30
percent of the patients survive the first five years after diagnosis.
BRIEF PROFILE
PROF. DR. WOLFGANG
HIDDEMANN
Director of the Department of
Internal Medicine III,
University Hospital of Munich,
chair of Internal Medicine
with a focus on hematology
and o ncology at Ludwig-
Maximilians-Universität
München, head of the Clinical
Cooperation Group “Pathogenesis of Acute Myeloid Leukemia”
Normal cells
Acute myeloid
leukemia
MAPK
Acute myeloid
leukemia + inhibitor
N676K
MAPK
N676K
MAPK
1992–1998: Director of the
Department of Hematology
and Oncology, University of
Göttingen
1986: Senior physician at the
University Hospital Münster
1978–1979: Research fellow
at the Memorial Sloan Kettering Cancer Center, New York
1976–1992: Clinical training
in the Department of Medicine
A, University of Münster
1975–1976: Medical assistant in
the Institute of Pathology at the
University of Münster, the
Department of Medicine at the
University Hospital of Münster
and the Surgical Department at
the Mathias Spital Rheine
Normal cell
The mutation N676K is a new target for the treatment of acute myeloid leukemia. Patients with
this mutation can be identified by this marker, and the uncontrolled cell growth can be inhibited
by inhibitors of the growth-regulating FLT3 receptor.
Cancer cell
84 BRIEF PROFILE
PROF. DR. DIRK EICK
Molecular Epigenetics at the
Institute of Clinical Molecular
Biology and Tumor Genetics,
leader at the Institute of Clinical
Molecular Biology and Tumor
Genetics
1983–1989: Postdoc, University
of Freiburg, Habilitation
Original Publications:
Corinna Hintermair et al.:
Threonine-4 of Mammalian
RNA Polymerase II CTD is
Targeted by Polo-Like Kinase 3
and Required for Transcriptional Elongation. The EMBO Journal 31 (2012) 2784-2797 | doi:
10.1038/ emboj.2012.123
Andreas Mayer et al.: CTD
Tyrosine Phosphorylation
Impairs Termination Factor
Recruitment to RNA Polymerase
II. Science 336 (2012) 1723 -1725
| doi: 10.1126/science.1219651
Corinna Hintermair, Martin
Heidemann, Rob D. Chapman –
Research unit Molecular
Epigenetics
Andrew Flatley, Elisabeth
Kremmer – Institute of Molecular Immunology
85 Further Decryption of
the Epigenetic Code
Proteins
The central function of the enzyme RNA polymer
ase II is the transcription of genetic information
stored in the DNA into mRNA, which then transports this information from the cell nucleus to
the ribosomes and there regulates protein biosyn
thesis. In addition, however, RNA polymerase II –
as has recently been discovered – is also crucial
whenever epigenetic information is stored in
the cell and retrieved again. Scientists of the
research unit Molecular Genetics, together with
colleagues from Ludwig-Maximilians-Universität
München and the Universities of Marseille and
Barcelona, have explored important new details
of these mechanisms.
With many slight alterations of amino acids, cells
are able to store information in the chromatin
of the cell, in order to transcribe this later when
needed or to delete it. The RNA polymerase II is
directly involved in this process with its carboxy
terminal domain (CTD) – a sequence of seven
amino acids repeated 52 times. As Dirk Eick and
his colleagues have now found, not only are
the serine amino acids reversibly modified in
the CTD by means of phosphorylation, but also
the amino acids threonine and tyrosine. The
combinatorics of how the large number of these
three amino acids is altered in the RNA polymerase II regulates important flows of information
in the cell and is the central component for the
regulation of gene expression in all multicellular
organisms. The CTD of RNA polymerase II thus
has the function of linking genetic and epigenetic
information in the cell. This further decryption
of epigenetic mechanisms enables a better
understanding of the molecular process of cell
differentiation, as well as pathological and
degenerative developments in the cells. Among
other research questions, the scientists want to
investigate how certain environmental factors
can influence the cells epigenetically.
Scientists of the research unit Molecular Epigenetics, in collaboration with colleagues from other institutions, have decrypted
mechanisms that control the cell nucleus enzyme RNA polymerase
II so that selected genetic and epigenetic information is processed.
The elucidation of such processes is a basis for better understanding diseases, and for developing new therapeutic approaches.
The term epigenetics refers to the genomic regulation mechanisms which are not specified in the DNA sequence. Epigenetic
modifications, e.g. the methylation of histone components of the
chromosomes, can contribute to determining the fate of genes and to
a certain extent can be passed on to subsequent generations.
Pol II
Histones with DNA
CTD (carboxy
terminal domain)
Y S P T S P S
P
P
cABL kinase
Polo-like kinase
RNA Polymerase II (POL II) transcribes the information of all protein-coding genes into mRNA and
is a central hub for storage and retrieval of epigenetic information in the cell. The carboxy terminal
domain (CTD) thus links genetic and epigenetic information.
86 BRIEF PROFILE
PD DR. TIM-MATTHIAS STROM
Research group leader at the
Institute of Human Genetics,
1992–2001: Physician, Medical
Genetics, University Hospital
of Ludwig-Maximilians-
1987–1992: Physician, Children’s Hospital of Technische
Anita Rauch et al.: Range of
Genetic Mutations Associated
with Severe Non-Syndromic
Sporadic Intellectual Disability:
an Exome Sequencing
Study. The Lancet 380 (2012)
1674-82 | doi: 10.1016/S01406736(12)61480-9
Elisabeth Graf, Thomas
Meitinger, Thomas
Schwarzmayr,
Thomas Wieland – Institute of
Human Genetics
Harald Grallert – Research unit
Christa Meisinger – Institute of
Epidemiology II
87 Intellectual Disability
Is Caused by
Spontaneous Mutation
New Insights into the
Genetic Mechanisms of
Red Blood Cell Formation
Severe congenital intellectual disability, which is
not associated with a known disease syndrome
such as Down syndrome, is caused to a high percentage by new mutations in the genome of the
child and is not inherited from the parents to the
child. This is the result of a study by researchers
from the Institute of Human Genetics, Helmholtz
Zentrum München, which they carried out
together with partners from the network ‘Mental
Retardation’ in the National Genome Research
network (NGFN) and with researchers from the
Universities of Erlangen, Essen and Zurich. To
this end, the scientists studied the genomes of
51 patients who were affected by congenital
intellectual disability and the genomes of their
parents. Tim Strom and Thomas Meitinger of
the Institute of Human Genetics carried out
exome sequencing for the mutation analyses in
which selectively the DNA segment was investigated that encodes proteins and other functional
Disturbances in red blood cell formation often
lead to anemia. This is a common condition
that can cause cognitive impairment, growth
retardation, and impaired physical capacity.
Scientists of the Institutes of Genetic Epidemiology, Epidemiology I, and Epidemiology II
of Helmholtz Zentrum München have been
instrumental in the identification of a total of 75
independent loci that play an important role in
human red blood cell formation. For this purpose, a genome wide association study (GWAS)
was carried out on 135 000 individuals.
For 43 of the identified 75 genes, no association
with parameters of erythrocytes (red blood cells)
had hitherto been detected. The identified genetic
loci contribute to the variance of the properties
of the erythrocytes in the general population. In
collaboration with research groups from the UK
products. In comparison to a control group, they
identified in the genomes of the patients a
significantly higher number of point mutations
and small insertions and/or deletions. In
particular, the number of mutations leading to
significant damage of the respective protein
was increased. The mutations were found in
many different genes, and only in a few genes
did the researchers find new mutations in more
than one person. The authors of the study
conclude that a large proportion of severe congenital intellectual disability is probably caused
by new mutations. With the aid of exome
sequencing, intellectual disability will be able
to be diagnosed much faster and more easily.
The scientists assume that in the future, the
method will become a standard procedure. The
good news for the affected parents is that in
future pregnancies there is only a slight risk of
having a child with an intellectual disability.
and the Netherlands, the research groups led
by Christian Gieger and Janina Ried of the
Institute of Genetic Epidemiology, Christine
Meisinger of the Institute of Epidemiology II and
Angela Döring of the Institutes of Epidemiology
I and II studied a total of six parameters of red
blood cells, including the number and size of the
erythrocytes and the hemoglobin values. Further
biological analyses provided insights into biological mechanisms and signaling pathways in the
formation and function of erythrocytes, which
shall be studied in more detail in future research
projects. These findings may then also contribute
to a deeper understanding of genetic abnormalities of blood cells and congenital forms of anemia. In subsequent studies, the researchers want
to identify genetic factors influencing clinically
relevant abnormalities of the red blood cells.
Congenital intellectual disability, which is not associated with
a known disease syndrome, is often – so the results of exome
sequencing – caused by spontaneous mutations in the genome of
those affected. Since the mutations are thus not inherited, there is
low risk of recurrence in another pregnancy.
By means of a genome-wide association study (GWAS), researchers
have identified 75 gene loci that play a role in human red blood cell
formation, enabling them to take a closer look at hematological
abnormalities such as anemia.
Intellectual disability (ID) affects about two percent of the
Genome wide association studies (GWAS) are advanced
p opulation. Although most cases have an underlying genetic cause,
to date only a few genetic defects have been identified.
a nalysis techniques used to detect genetic differences between
healthy subjects and people with conditions such as anemia or
diabetes. The aim is to identify associations between genetic
variations and external characteristics and thus to identify genetic
risk factors for the development or course of a disease.
BRIEF PROFILE
DR. CHRISTIAN GIEGER
Genetic Epidemiology and
KORA-gen, Institute of Genetic
Epidemiology, Helmholtz
Zentrum München
Hertwig Award for Interdis
ciplinary Cooperation
since 2004: Research associate
and project leader of KORA-gen
1999–2004: Researcher in
industry and at the Fraunhofer
Institute St. Augustin
1994–1998: Research associate
at Ludwig-MaximiliansUniversität München
Pim van der Harst et al.: SeventyFive Genetic Loci Influencing
the Human Red Blood Cell.
Nature 492 (2012) 369-378 | doi:
10.1038/nature11677
Janina S. Ried – Institute of
Christine Meisinger – Institute
of Epidemiology II
Angela Döring – Institute of
Epidemiology I, Institute of
Epidemiology II
Thomas Illig – Research unit
88 BRIEF PROFILE
DR. MELANIE WALDENBERGER
Complex Diseases,
Epidemiology
2003–2012: Research a ssociate
at Ludwig-Maximilians-
Universität and Helmholtz
Zentrum München
Ann-Kristin Petersen et al.:
Epigenetics Meets Metabolomics: An Epigenome-Wide
Association Study with Blood
Serum Metabolic Traits. Human
Molecular Genetics 23 (2014)
534-545 (Epub 2013 Sep 6) | doi:
10.1093/hmg/ddt430
Ann-Kristin Petersen, Markus
Brugger, Konstantin Strauch, –
Institute of Genetic Epidemiology
Sonja Zeilinger, Harald
Grallert – Research Unit
Gabi Kastenmüller, Werner
Römisch-Margl, Karsten Suhre –
Institute of Bioinformatics and
Systems Biology
Annette Peters, Christine
Meisinger, Institute of
Epidemiology II
Jerzy Adamski, Institute of
Experimental Genetics –
Genome Analysis Center
89 DNA Methylation Plays
Important Role in
Human Metabolism
Aging processes, but also environmental and
lifestyle factors such as smoking or diet cause
biochemical modifications in the DNA during the
course of a lifetime. This can lead to methylation
of the DNA components, whereby methyl groups
are added without changing the actual DNA
sequence. These processes, known as epigenetic
changes, can impact gene function. Scientists
of the Institute of Genetic Epidemiology and the
Research Unit Molecular Epidemiology carried
out an epigenome-wide association study to
determine if there are any associations – and
if so which associations – between epigenetic
processes and health consequences for the
metabolism. For this purpose, the team led by
Christian Gieger and Melanie Waldenberger in
collaboration with Karsten Suhre from Weill
Cornell Medical College in Qatar analyzed blood
samples of more than 1800 participants of the
KORA study (Cooperative Health Research in the
Augsburg Region). In the samples they analyzed
more than 457 000 positions in the DNA to detect
epigenetic alterations and compared these with
concentrations of 649 different metabolites. The
analysis showed that methylation of 28 DNA segments changed a number of important metabolic
processes.
In the respective DNA regions, already known
disease-associated genes were also found, such
as the gene TXNIP, which regulates glucose metabolism and is associated with the development
of diabetes mellitus. Consistent with this finding,
altered concentrations of metabolites of the
lipid and glucose metabolism were found in the
methylated TXNIP. Moreover, genes that can be
biochemically altered by smoking affect different
metabolic activities.
The study provides new insights into how
lifestyle factors can influence the metabolism
through DNA alterations. The results will be
used to develop new diagnostic and therapeutic
approaches for lifestyle-related diseases.
Lifestyle factors can alter DNA and thus have an impact on the
metabolism and cause disease. In an epigenome-wide association
study, scientists of Helmholtz Zentrum München have identified 28
DNA alterations that are associated with metabolic changes.
Biological functions of organisms are also controlled by higher-
level regulatory mechanisms, which are grouped under the term
epigenetics. Epigenetic modifications, such as methylation of
protein components of chromosomes, can help to determine the
fate of genes and are passed on to some extent even to subsequent
generations.
CpG
methylation
1
5
Genetic
variant(s)
4
Gene
expression
Concentra
tion(s) of
metabolites
6
2
Efficiency of
enzymatic
reactions
3
Schematic view of processes through which genetic variance and CpG methylation can be
influenced in the metabolism. Possible feedback reactions are depicted by dashed lines.
1
variant in CpG site
2
variant in
coding region
3
biochemical
transformation(s)
4
variant in generegulatory element
5
methylation in generegulatory element
6
availability of
gene-product
90 BRIEF PROFILE
DR. JAN KRUMSIEK
Systems Metabolomics, Institute of Computational Biology,
2013 to the present: Helmholtz
Postdoc Program,
Initiative and Networking Fund
2013: Doctoral Award
Technische Universität
München and Helmholtz
Doctoral Award
2012: Graduate Students‘
Award Helmholtz Zentrum
München
BRIEF PROFILE
DR. GABI KASTENMÜLLER
Metabolomics at the Institute
of Bioinformatics and Systems
Biology, Helmholtz Zentrum
München
since 2014: Honorary Lecturer,
King‘s College London, UK
2009-2011: Postdoc, Institute
of Bioinformatics and Systems
Biology
2010: Guest scientist at
Metabolon Inc., USA
2009: PhD, Technische
Jan Krumsiek et al.: Mining the
Unknown: A Systems Approach
to Metabolite Identification
Combining Genetic and Metabolic Information. PLoS Genetics 8 (2012) e1003005 | doi:
10.1371/journal.pgen.1003005
Karsten Suhre, Brigitte Wägele,
Werner Römisch-Margl, Fabian
J. Theis – Institute of Bioinformatics and Systems Biology
Thomas Illig – Research Unit
Jerzy Adamski – Institute of
Christian Gieger – Institute of
91 Detecting the Identities of
“Unknown Metabolites”
Imaging Modalities –
two better than one
A combined analysis of genetic variants and
actual metabolic changes shows relationships
between risk factors and the development of
common diseases and thus provides evidence
of standardized measurable biomarkers. Thus
far, however, only such metabolites could be
considered that the measuring devices recognize. The research team led by Jan Krumsiek and
Gabi Kastenmüller of the Institute of Bioinformatics and Systems Biology and the Institute
of Computational Biology has developed a
method to also identify unknown metabolites.
The application of the method on risk factors
that have not been chemically characterized
until now allows conclusions to be drawn about
which processes influence the development of
disease, but also about the individual’s response
to drug therapies. On the basis of data from
the KORA population study (Cooperative Health
Scientists of the Institute of Biological and
Medical Imaging and the Institute of Experimental Genetics led by Vasilis Ntziachristos have
achieved a milestone in imaging diagnostics: By
combining two established, non-invasive imaging techniques – X-ray computed tomography
(XCT) and a camera-based hybrid fluorescence
molecular tomography (FMT) system – they succeeded for the first time in obtaining a 360-degree view from the inside of a living organism.
With the combined XCT-FMT method, which
combines the advantages of the two proven
imaging techniques, internal structures and
organs can be examined in detail in the living
organism. For example, it is possible – due to
the 360° view – to exactly localize pathologically
altered tissue in vivo. Through the combination
of the two methods, significantly better results
can be achieved than with a stand-alone
method. In living mice the scientists were able
Research in the Augsburg Region), the scientists
detected in the blood the biochemical identity
of nine previously unknown metabolites and
associated 97 compounds to specific metabolic
pathways, including risk factors for high blood
pressure and insulin resistance. A new marker
for impaired liver detoxification may in the future
be a chemical derivative of vitamin C whose
concentration is also genetically influenced.
This blood value can indicate to the physician
how effectively the liver detoxifies a patient’s
body and thus aid in the selection of a suitable
drug for this particular patient. Personalized
therapies that are based on a combination of
genetic and biochemical risk factors can offer
chances of an improvement the quality of life
or a cure of common diseases, such as type 2
diabetes, which is currently incurable.
to observe bone growth, obtain images of
subcutaneous tumors in the neck area in high
resolution and to diagnose lung cancer. The
new combination of the two methods enables
more precise diagnosis as to where the tissue
is pathologically changed than when the techniques are used individually.
In further steps, the scientists want to refine
this in-vivo method so that it can be used in
pre-clinical diagnosis in patients – for example
in the early detection of tumors. The Institute
of Biological and Medical Imaging explores in
vivo imaging technologies for the life sciences.
It develops systems, theories and methods for
imaging and image reconstruction as well as animal models for the testing of new technologies
on the biological, pre-clinical and clinical level.
The aim is to provide innovative tools for the bio
medical laboratory, for diagnostics and for the
monitoring of therapies for human diseases.
Scientists at the Institute of Bioinformatics and Systems Biology have
developed a method to identify previously unknown metabolites in
the blood that may be associated with genetic variations. This could
be a further boost for the development of personalized therapies.
Scientists of the Institute of Biological and Medical Imaging have
combined two well-established imaging techniques – X-ray based
computed tomography and fluorescence molecular tomography – in
such a way that a detailed 360-degree view of the inside of a living
organism is possible.
Metabolomics is the study of the characteristic metabolic traits of
an organism that are present in the metabolites of a blood s ample.
The analysis is performed via mass spectrometry or magnetic
resonance imaging.
In X-ray based computed tomography, different images
taken with the aid of x-ray are assembled in the computer to p rovide
three-dimensional visualization of the investigated structures. In
fl
uorescence tomography the distribution of a fluorescent
substance which was administered prior to the test is shown three-
dimensionally and non-invasively in the tissue and organs.
BRIEF PROFILE
PROF. DR. VASILIS
NTZIACHRISTOS
Institute Director and chair of
Biological and Medical Imaging
and Technische Universität
München
2013: Gottfried Wilhelm
Leibniz Prize of the German
Research Foundation
2011: Erwin Schrödinger Prize
of the Helmholtz Association
and the Founders‘ Association
for German Science, Basic
Science Award of the Academy
of Molecular Imaging (AMI)
2010: Heinz Maier-Leibnitz
Medal of Technische
2008: European Research
Council Advanced Investigator
Award
2002–2007:Assistant Professor,
Harvard University Medical
School and Massachusetts
General Hospital
2004: Top 100 of the World’s
Young Innovators
until 2001: Postdoc, Harvard
University
Angelique Ale et al.: FMT-XCT:
in Vivo Animal Studies With
Hybrid Fluorescence Molecular
Tomography-X-Ray Computed
Tomography. Nature Methods
9 (2012) 615-622 | doi: 10.1038/
nmeth.2014
Angelique Ale, Vladimir Ermolayev, Eva Herzog – Institute of
Biological and Medical
Imaging
Christian Cohrs, Martin Hrabe
de Angelis – Institute of
92 2007–2011: Senior scientist,
Hertwig Award for Interdis
ciplinary Cooperation
2000–2007: Postdoc scientist,
European Molecular Biology
Laboratory (EMBL)
BRIEF PROFILE
TAO XU
Doctoral student, Research Unit
Molecular Epidemiology,
Institute of Epidemiology II,
Tao Xu et al.: Effects of Smoking
and Smoking Cessation on
Human Serum Metabolite
Profile: Results from the KORA
Cohort Study. BMC Medicine 11
(2013) 60 | doi: 10.1186/17417015-11-60
Christina Holzapfel, Erik Bader,
Zhonghao Yu, Katrin Perstorfer,
Marta Jaremek, Thomas
Illig – Research Unit Molecular
Epidemiology
Cornelia Prehn, Jerzy Adamski –
Institute of Experimental
Genetics
Werner Roemisch-Margl,
Fabian Theis, Karsten Suhre –
Systems Biology
H.-Erich Wichmann – Institute
of Epidemiology I
Karl H. Ladwig, Annette Peters
Lifestyle Factors Affect
Metabolite Profile
Cigarette smoking causes a multitude of changes
in metabolite concentration, which increase the
risk of multiple diseases. When an individual
quits smoking, smoking-related changes in
human serum metabolites are reversible. These
results are consistent with previous findings
that the risk for cardiovascular disease – such
as a myocardial infarction – reduces after
smoking cessation. Scientists of the Research
Unit Molecular Epidemiology, of the Institute of
Epidemiology II and of the Institute of Experimental Genetics analyzed blood samples from
more than 1 200 participants of the populationbased Cooperative Health Research in the
Region of Augsburg (KORA) cohort. Blood samples and smoking status of these individuals
were collected at two time points: a baseline
survey conducted between 1999 and 2001 and
a follow-up after seven years. Overall, through
the analysis of the metabolite profiles, the team
led by Rui Wang-Sattler, Tao Xu, Jerzy Adamski
and Annette Peters identified 21 smokingrelated metabolites, which are enriched in amino
acid and lipid pathways. 19 out of the 21
metabolites were found to be reversible in
former smokers, including arginine, glutamate
and lyosphosphatidylcholines, which have
been previously preported to be associated
with the risk reduction of cardiovascular diseases.
These results indicate the remarkable benefits of smoking cessation and provide a link to
cardiovascular disease benefits.
The identified smoking-related metabolites
pinpointed disturbed pathways, which are
useful to elucidate further health consequences
of nicotine consumption. The study therefore
represents a meaningful metabolomics
approach with which the molecular signatures
of lifestyle-related environmental exposures
and diseases can be studied.
ornithine
Head of the research group
Metabolism, Research Unit
Molecular Epidemiology,
Institute of Epidemiology II,
10
Smokers
5
Former smokers
Never smokers
0
1st study
2nd study
7 years
PC ae C38:6
BRIEF PROFILE
DR. RUI WANG-SATTLER
93 0.0
-0,5
-1
-1,5
1st study
2nd study
7 years
Smoking-related changes in human serum metabolites are reversible after smoking cessation, consistent with the known cardiovascular risk reduction and other health consequences.
Concentrations of the metabolite arginine and ornithine in the blood of smokers, former smokers
and never smokers: The data of the two studies were collected with an interval of seven years.
The Cooperative Health Research in the Region of
Augsburg (KORA) has been studying the health of thousands of
people from the Augsburg area for almost 30 years. The aim is to
understand the effects of environmental factors, behavior and genes.
The core topics of the KORA studies are questions about the development and course of chronic diseases, in particular heart attack and
diabetes mellitus. To this end, research is conducted on risk factors
from health behavior, the environment and genetics.
94 BRIEF PROFILE
PROF. DR. DR. FABIAN J. THEIS
Computational Biology,
Helmholtz Zentrum München,
chair of Mathematical
Models of Biological Systems
of T echnische Universität
München
2008–2012: Junior group leader
at the Institute of Bioinformatics and Systems Biology,
2010: Starting Grant of the
European Research Committee
(ERC)
2008: Habilitation
2006–2007: Bernstein Fellow
at the Bernstein Center for
Computational Neuroscience
Göttingen
2003–2006: Research stays in
Japan, USA, Finland
BRIEF PROFILE
DR. FLORIAN BÜTTNER
Machine Learning, Institute
of Computational Biology,
Systems Biology, Helmholtz
Zentrum München
2007–2011: Assistant, The
Institute of Cancer Research,
University of London
95 Bioinformatics for
Stem Cell Research
Scientists of the Institute of Computational
Biology at Helmholtz Zentrum München, together
with colleagues from the Stem Cell Institute and
the Institute for Medical Research of the University of Cambridge, have identified important
differentiation pathways of stem cells. The Munich
scientists were responsible for the characterization of transcriptional networks in blood stem and
progenitor cells using high-throughput single-cell
gene expression analysis.
Out of a pool of nearly 600 single primary blood
stem and progenitor cells isolated from mouse
bone marrow, 18 transcription factors were
identified which can cause a further differentiation of the progenitor stem cells. Transcription
factors are responsible for turning gene expression “on” or “off”. By means of a statistical
mapping technique known as dimensionality
reduction, Florian Büttner and Fabian Theis
identified specific patterns in the pairings of
these transcription factors. The pairings could
be correlated positively or negatively with
characteristic stages of cell maturation and
therefore provided clues about the functions
of the individual transcription factors and the
cell fate. Within the expression patterns, the
scientists also found previously unrecognized
relationships between the factors Gata2, Gfi1
and Gfi1b. This is of particular importance
because especially for Gata2 and Gfi1, recently
a correlation has been described with leukemia:
Gata2 is thought to promote the formation of
malignant cell clones, whereas Gfi1 plays a
more protective role.
The reconstruction of individual transcription
factor profiles and the identification of their
networks offer the opportunity not only to
unders tand the physiological differentiation
and development of cells, but to better understand degenerative and malignant processes.
TEL
ERG
ETO2
SCL
FLI1
Direct proteinprotein interactions
RUNX1
GATA1
PU.1
GATA2
NFE2
GFI1
MITF
GFI1B
MEIS1
HHEX
LYL1
In collaboration with the University of Cambridge, scientists of the
Institute of Computational Biology have identified important differentiation pathways of stem cells by means of expression patterns of
transcription factors.
Functional
relationships
LMO2
LDB1
Network of 18 transcription factors involved in the differentiation of bone marrow stem cells into
various blood and immune cells
Victoria Moignard et al.:
Characterization of Transcriptional Networks in Blood Stem
and Progenitor Cells Using
High-Throughput Single-Cell
Gene Expression Analysis.
Nature Cell Biology 15 (2013)
363-372 | doi: 10.1038/ncb2709
Cell differentiation is regulated by a complex interaction of
e xternal influences on the internal cell environment, in which
so-called transcription factor-regulated-networks are of particular
importance. Transcription factors are responsible for activating or
repressing gene expression.
96 BRIEF PROFILE
DR. KLAUS MAYER
Head of the Department
Genome and Systems Biology
of Plants, Helmholtz Zentrum
München
leader at the Institute of
Bioinformatics and Systems
Biology
1997–1999: Research a ssociate
at the Munich Institute for
Protein Sequences (MIPS),
the Max Planck Institute of
Biochemistry, Munich
1993–1997: Research assistant,
Ludwig-Maximilians-Universität
München and the University of
Tübingen
The International Barley
Sequencing Consortium, Klaus
Mayer et al.: A Physical,
Genetic and Functional Sequence
Assembly of the Barley
Genome. Nature 491 (2012) 711716 | doi: 10.1038/nature11543
Rachel Brenchley et al.: Analysis of the Bread Wheat Genome
Using Whole-Genome Shotgun
Sequencing. Nature 491 (2012)
705-710 | doi: 10.1038/nature11650
Thomas Nussbaumer, Heidrun
Gundlach, Mihaela Martis,
Manuel Spannagl, Matthias
Pfeifer – Department Plant
Genome and Systems Biology
97 Mapping of the
Barley and Bread
Wheat Genomes
In the framework of the International Barley
Sequencing Consortium, scientists at the
Helmholtz Zentrum München have made a
major contribution to deciphering and analyzing the barley genome and to develop new
approaches for molecular breeding.
The research of the International Barley Sequencing Consortium, which along with other
partners, includes scientists led by Klaus Mayer
at the Department of Plant Genome and Systems
Biology, provides a detailed view into the barley
genome. For the first time a high-resolution
genome overview was created for a genome that
by far exceeds the size of the human genome.
In addition, the team was able to gain insight
into gene regulation and make comparisons
between wild barley and cultivated strains.
Thus, an in-depth molecular understanding
of the inventory of cereal genomes and a first
glimpse into molecular circuits was obtained.
The findings are seen as an important basis to
accelerate the breeding of barley varieties that
e.g. show improved resistance or are better
adapted to climate change. At the same time, the
barley genome served the researchers as model
for the more complex bread wheat genome.
Here the team headed by Klaus Mayer, together
with British scientists from the Universities of
Bristol und Liverpool and the John Innes Centre
carried out and published a first genome analysis. Along with rice and corn, wheat is the most
important cereal crop. The bread wheat genome
is hexaploid (contains six copies) and contains
approximately 96 000 genes. Due to its size and
complexity, it has not yet been fully sequenced.
The now published genome gene atlas is an
important step towards understanding the
interplay of the different genome copies of this
cereal and to enable molecular breeding even
for wheat.
Together with international partners, a team of the Department of
Plant Genome and Systems Biology has created ordered sequence
resources of the highly complex genomes of barley and bread wheat.
Both crops are of enormous importance.
Barley is one of the earliest domesticated and most important cereal
crops. The barley genome is diploid, contains slightly more than
26 000 genes and includes 5.1 billion base pairs (5.1 Gb). The bread
wheat genome, with 17 billion base pairs (17 Gb), is not only
much larger but also contains considerably more genes – approximately 96 000. A wheat cell is hexaploid and has six copies of its
chromosomes.
Casting Light on the
Evolution of Nightshades
The Tomato Genome Consortium (TGC), a group
of more than 300 scientists from 14 countries,
has sequenced the genome of the domesticated
tomato and its closest wild relative (Solanum
pimpinellifolium). Together with other research
centers in Germany, Helmholtz Zentrum München
was involved in the bioinformatics analysis and
annotation of the genome sequences.
The research group led by Klaus Mayer at the
Department of Plant Genome and Systems Biology
was responsible for data management, database
infrastructure and dissemination as well as gene
family and comparative genome analyses. The
sequences provide the most detailed insights to
date into the tomato genome. Thus, the approximately 35 000 genes of the tomato with their
genomic position and a large portion of their
likely functions are now known.
The tomato is a member of the Solanaceae
or nightshade family. The Solanaceae family
includes potatoes, bell peppers and eggplant.
Worldwide, it is the most important family of
vegetable plants – both with regard to its economic significance and the quantity produced.
Members of the Solanaceae family are used as
food, spices and as medicinal plants. The new
sequences provide a reference to identify important genes in related species.The sequences also
open up insights into the diversification of the
tomato and the adaptation to new environmental
conditions.
They reveal that 60 million years ago triplication of the tomato genome occurred. After
that, a large part of the triplicated genes were
lost. However, some exist even until today and
control the most important breeding traits of
the tomato including strength, fleshiness and
fruit coloring.
The results are an important basis for further
research to optimize the production of tomatoes and other crops. The resistance to pests,
diseases and drought, which in part have been
lost during the domestication of the plant, is of
particular importance.
With the participation of Helmholtz Zentrum München, the Tomato
Genome Consortium, a group of more than 300 scientists from 14
countries, has sequenced the tomato genome with its approximately
35 000 genes. The Department of Plant Genome and Systems Biology
manages a range of several plant genome databases, provided
important infrastructure for the data management and carried out
gene family and comparative genome analyses.
In gene sequence annotation, the position of exons and introns,
protein-encoding regions including the encoded protein and its
possible functions, promoter elements and repetitive DNA elements is
attached (annotated) to the actual DNA sequence.
The Tomato Genome Consortium: The Tomato Genome
Sequence Provides Insights into
Fleshy Fruit Evolution. Nature
485 (2012) 635-641 | doi:
10.1038/nature11119
Manuel Spannagl, Heidrun
Gundlach, Remy Bruggman –
Institute of Bioinformatics
and Systems Biology/Munich
Information Center for Protein
Sequences (MIPS)
98 BRIEF PROFILE
PD DR. ANTON R. SCHÄFFNER
Institute of Biochemical Plant
Pathology, Helmholtz Zentrum
München
1996: Habilitation
1990–1997: Research
group leader, Institute of
Biochemistry, Gene Center
of Ludwig-Maximilians-
99 How Roots Branch Out
Plants initiate lateral root formation deep within the primary root. For lateral roots to reach
the soil, they first must break through the rigid,
overlying tissue layers of the primary root.
To initiate lateral root emergence, the plant
hormone auxin is required. This also stimulates processes to weaken the cell walls. In the
current study, it was found that the increased
auxin concentration also causes aquaporin
expression to change in the cell membranes
of the new organ and the surrounding tissue. Aquaporins facilitate water movement
across the cell membranes of plant cells. This
regulation is also critical for how rapidly the
newly initiated lateral roots can penetrate the
tissue. The researchers led by Anton Schäffner
at the Institute of Biochemical Plant Pathology
have conducted research on this topic together
with colleagues from the Centre for Integrative
Plant Biology of the University of Nottingham in
the UK, the Institut Nationale de la Recherche
Agronomique in Montpellier, France, and the
Universidad de Extremadura, Badajoz, Spain.
Researchers at Helmholtz Zentrum München
investigated in particular the phenotypes of
plants whose aquaporin expression had been
genetically modified and determined the temporal and spatial expression patterns of aquaporins
in the emerging lateral root. The colleagues in
France contributed essential physiological data.
Mathematical modeling based on the experimentally found expression patterns was also
crucial; it enabled enabled the British partners
to correctly predict the phenotypic findings. The
consortium’s insights gained on the model plant
Arabidopsis thaliana (thale cress), may be useful
for plant breeding: Through the formation of
lateral roots, plants not only have a better grip
in the soil but can also absorb more water and
minerals. This is a great advantage for plant
growth – especially with reduced water availability in soils due to climate change.
Longitudinal section
of a root
Experimental system for lateral root formation: Lateral roots are specifically induced at the
bend of the primary root, which is formed due to the changed direction of gravity after a 90°
rotation of the plants. Thus, a synchronous development of the new organ can be achieved,
which p
rogresses through eight stages, as is depicted in the root longitudinal sections.
The expression of aquaporins is locally regulated by the increased
auxin levels that initiate lateral root formation. These changes
significantly affect the rate of lateral root emergence.
Benjamin Péret et al.: Auxin
Regulates Aquaporin Function
to Facilitate Lateral Root Emergence. Nature Cell Biology 14
(2012) 991-1006 | doi: 10.1038/
ncb2573
Jin Zhao, Olivier Da Ines –
Institute of Biochemical
Plant Pathology
Aquaporins are proteins in the cell membrane of organisms that
regulate water permeability. Thus, they also influence the rate of
pressure changes within plant cells driving their expansion growth.
Innovation
and Translation
Innovation management and the management of translational and c linical
projects at Helmholtz Zentrum München are dedicated to promote the
improvement of health. They support the development of patient-oriented
research towards concepts for clinical applications and drug development.
Helmholtz Zentrum München turns promising
scientific approaches from basic research into
innovations. It ensures that all innovative knowhow being produced at the Center is protected
by patents and out-licensed for commercialization. Insights from basic research are further
developed and applied in spin-offs and in collaborations with competent industrial partners.
Trianta Immunotherapies GmbH was founded in
2013 as a spin-off of the Institute of Molecular
Immunology and develops immunotherapies for
the treatment of cancer. For its spin-off p roject,
the team led by Institute Director Prof. Dr.
Dolores Schendel received an m4 award of the
Bavarian Ministry of Economic Affairs endowed
with 500 000 euros.
In 2012 and 2013, four new companies were
launched as spin-offs from Helmholtz Zentrum
München. Thus, the Center translates excellent
science into specific applications and creates
new impetus in the field of data management,
clinical imaging, immunotherapy and radiation
dosimetry.
Dosimetrics GmbH was also founded in 2013. The
company is a manufacturer and service provider
of personal dose monitoring systems for ionizing
radiation. Based on the research of the personal
dosimetry service at Helmholtz Zentrum M
ünchen,
the largest personal dosimetry service in Europe,
Dosimetrics provides technologies for easy detection and the rapid readouts of individual doses.
Clueda AG, founded in 2012, is a software
company that brings intelligent prediction,
analysis and decision support tools to market
maturity for different industries. In 2013 the
company received the Best in Big Data Award
of the weekly magazine Computerwoche for
an a nalysis system it developed together with
a German investment bank.
The start-up company SurgVision B.V., launched
in 2013, develops systems that enable molecular live imaging during surgical procedures.
A first clinical study on image-guided surgical
procedures for breast cancer patients is nearing
completion, additional indications are being
evaluated.
SurgVision developed from a collaborative
project between the Institute of Biological and
Medical Imaging and the University Medical
Center Groningen, the Netherlands.
With the new start-up companies, Helmholtz
Zentrum München has continued its successful
series of spin-offs. Since 1997, 18 spin-off companies from the Center have been founded. 15
of these are currently active on the market and
employ approximately 400 people.
In the field of drug development, Helmholtz
Zentrum München specifically promotes projects
that are in the early phase of the value added
chain. The portfolio currently comprises developmental projects from the areas of diabetes,
neurodegeneration, autoimmune diseases and
cancer. The major aim is the identification and
development of innovative drugs. Five of the 27
newly registered patents in 2012 and 2013
refer to new compounds. The entire patent
portfolio of the Center currently covers 150
patent families.
To identify new target structures for drugs
against diabetes, a strategic research collaboration was launched in 2013 between the Institute
for D
iabetes and Obesity and Sanofi Aventis
Deutschland GmbH. The research collaboration is
initially designed to last for three years.
Translational Research
Translational research, which aims at the benefit
for patients, is an essential element of the
scientific strategy at the Center. The objective
is to enable the reliable stratification of patient
groups and to develop preventive and treatment
approaches tailored to the individual patient.
Key success factors are the close connection
between excellent basic research, continuous
advancements in platform technologies and differentiated model systems with large population
cohorts, and clearly defined patient populations.
The Center implements this principle in three
translational centers, eleven clinical cooperation
groups and a translational project portfolio in
collaboration with clinical partners.
Translational Centers
There are three regional translational centers
in the fields of lung, diabetes and allergy
research that closely combine basic research,
technology platforms and clinical research in a
long-term perspective. While both the Diabetes
Study Center and the Munich Allergy Research
Center collaborate with Technische Universität
München, translational research in cooperation
with Ludwig-Maximilians-Universität München
and the Asklepios Fachkliniken München-Gauting
has been implemented at the Comprehensive
Pneumology Center since 2103, following the
successful appointment of the Chair of Clinical
Pneumology at the University Hospital.
Clinical Cooperation Groups
In eleven clinical cooperation groups, defined
clinical-scientific hypotheses are elucidated with
the aim of achieving clinical proof of concept.
Four of them develop personalized cellular
therapy approaches for clinical application. A
phase I/II trial for treatment of CMV infection
after bone marrow transplantation by adoptive
T-cell transfer was recently completed and is
being evaluated. Further projects in or shortly
prior to clinical trials include cell vaccination
in acute myeloid leukemia, NK-cell transfer in
non-small cell lung cancer and prophylactic CMV
and EBV-specific T-cell transfer after stem cell
transplantation.
Since 2013, two clinical cooperation groups have
been participating in observational studies of
the German Center for Diabetes Research (DZD).
For the Prediabetes Lifestyle Intervention Study
PLIS, these groups investigate whether lifestyle
changes with respect to diet and physical activity
positively influence the risk for the development
of type 2 diabetes. Within the German Diabetes
Study DDS, a differentiated long-term observation of newly diagnosed diabetes patients is
being carried out.
In cooperation with the Department of Radiation
Oncology, Ludwig-Maximilians-Universität München, the clinical cooperation group
"Personalized Radiotherapy in Head and Neck
Cancer" was established in 2013. It analyzes
molecular markers for predicting the efficacy of
radiotherapy for tumors of the head and neck area.
Translational Project Portfolio
To specifically strengthen the development of
personalized preventive, diagnostic and therapeutic concepts, translational and have been funded
since 2012. A total of nine peer-reviewed projects
were supported by 2013.
Cross-Program Initiative Personalized Medicine
In the newly established Helmholtz Initiative
Personalized Medicine (iMed), the Center has
teamed up with four Helmholtz Health Research
Centers to establish a research-driven and
molecular systems medicine program which
spans various indications. The initiative provides
high-throughput and IT platforms for collaborative projects. The indications are cancer,
metabolic and cardiovascular diseases, diseases
of the nervous system as well as lung diseases
and infectious diseases.
Innovation and
Translation
18
Spin-Offs from
the Center since 1997
Here we present two promising
new approaches for prevention and therapy.
INNOVAT ION AND T RANSLAT ION
104 Antipsychotic Drugs Tested
against Malignant Lymphomas
For Daniel Krappmann, in retrospect everything seems so clear and obvious. In view
of their groundbreaking findings, the excitement was palpable among Krappmann and
his 15-member team until the study was published: The researchers discovered that
specific drugs used since the 1950s to treat psychotic disorders can also be used as cancer
treatment against malignant lymphomas. The substances inhibit the enzyme MALT1
leading to the death of cancer cells. This could mean a breakthrough in cancer research.
105 Many years of intensive preparatory work, coupled with determination and the necessary
bit of luck led to this success. Since 2008, Daniel Krappmann, head of the research unit
Cellular Signal Integration at the Institute of Molecular Toxicology and Pharmacology at
Helmholtz Zentrum München, has been investigating the MALT1 protease, which he had
recognized as a particularly interesting enzyme. “It is the only enzyme in this class in
humans, and is thus very exclusive,” the 45-year-old biologist said. He not only analyzed
its enzymatic effectiveness, but using genetic methods, also explored the effects of the
MALT1 protease on the immune system. In addition, his team, together with scientists
from Technische Universität München, was able to show that aggressive lymphoma cells
are not viable without the activity of MALT1.
After all this was known, Krappmann decided to look for compounds that can inhibit
MALT1, since such substances would provide good starting points for drugs for the treatment of lymphomas or autoimmune diseases. His doctoral candidate Daniel Nagel took on
the task and tested 18 000 substances in cooperation with the Leibniz-Institut für Molekulare Pharmakologie in Berlin. After many test runs and further analyses in cooperation
with Charité Universitätsmedizin Berlin, it became apparent that the long-known antipsychotic drugs mepazine and thioridazine were among the best MALT1 inhibitors.
"It is a huge advantage that both drugs have long been in clinical use," said Krappmann.
"Many side effects have been extensively studied, and this allows us to quickly initiate
clinical trials." These will now begin parallel to further trials that will be carried out on
the effect of the substances in autoimmune diseases.
According to Krappmann, Helmholtz Zentrum München offers excellent conditions
for such research. Here researchers find expertise in a variety of disciplines, from
biochemistry and immune research to preclinical testing. Meanwhile, a separate
screening unit has been established for drug discovery at the Center.
Added to this was the financial support from the Helmholtz Validation Grant, the new
funding instrument of the Helmholtz Association. The funding for the project amounted to
around 950 000 euros, half of which came from the Helmholtz Association and the other
half from Helmholtz Zentrum München. The financial support from this fund shall enable
scientists from Helmholtz centers to develop their project ideas into commercial results
within two years. That is exactly what happened in Krappmann’s project.
The successful identification of a MALT1 inhibitor will also raise the awareness of the
pharmaceutical industry for developments and projects within the Helmholtz Association
and, over the medium term, significantly promote strategic partnerships. Thus, innovative
solutions for patients and even personalized medicine approaches will become possible:
“In the future, special biomarkers may enable the identification of patients who respond to
treatment with a MALT 1 inhibitor,” said Daniel Krappmann. “Our long-term goal is quite
clear – to replace standard treatment with personalized treatment, i.e. with a treatment
protocol designed for the individual patient.”
Daniel Krappmann is studying the MALT 1 protease enzyme as new approach for
the treatment of malignant lymphomas. With support from the Helmholtz Validation
Grant and the Department of Innovation Management, the team of the research unit
Cellular Signal Integration led by Krappmann found potential enzyme inhibitors,
which then were licensed for therapeutic further development. Image: signaling
protein visualized with an immunofluorescence microscope.
All in all, a great success for Innovation Management at Helmholtz Zentrum München.
Here in an exemplary way, basic research findings are translated into applications – thus
increasing the value creation of the Center immensely. “It is only possible to pursue such
research approaches consistently in an interdisciplinary research environment,” Krapp
mann said. “With our study we have shown that it really can be done!“
BRIEF PROFILE
PROF. DR. DANIEL
KRAPPMANN
Cellular Signal Integration and
deputy director of the Institute
of Molecular Toxicology,
since 2014:
Professor,
2011-2013:
Funding through Helmholtz
Validation Fund Grant
since 2008:
Privatdozent,
Ludwig-MaximiliansUniversität Munich
2005-2008:
Institute of Toxicology,
2005: Habilitation
2002 -2005:
Junior research group leader,
Max Delbrück Center, Berlin
1997-2002:
Postdoc, Max Delbrück Center,
Berlin
Publications:
Daniel Nagel et al.: Pharmacologic Inhibition of MALT1
Protease by Phenothiazines
as a Therapeutic Approach for
the Treatment of Aggressive
ABC-DLBCL. Cancer Cell 22
(2012) 825–837 | doi: 10.1016/j.
ccr.2012.11.002
Florian Schlauderer et al.:
Structural Analysis of Phenothiazine Derivatives as Allosteric
Inhibitors of the MALT1
Paracaspase. Angew. Chem.
Int. Ed. 52, 10384–10387 (2013) |
doi: 10.1002/anie.201304290
106 107 Spearhead of
Diabetes Prevention
The incidence of a disease is rising, and no one knows why: For years doctors have
observed that the number of cases of type 1 diabetes in children – especially young
children – and adolescents is rising throughout the world. In Germany, the rate of
new cases is currently increasing by three to five percent annually. The causes for
this increase are still unknown; possible culprits may be environmental factors that
have an effect in the womb or in early childhood, for example early nutrition, viral
infections or changes in the immune system through improved hygiene, but also the
development of the microbiome of the digestive system in early childhood and the
bacterial colonization of the intestine.
BRIEF PROFILE
DR. FLORIAN HAUPT
At the Institute of Diabetes Research at Helmholtz Zentrum München, scientists under the
direction of Anette-Gabriele Ziegler are seeking to find the causes of type 1 diabetes, to
elucidate the disease course and to combat the disease. Type 1 diabetes – in contrast to
the much more frequent type 2 diabetes – is triggered by an autoimmune process. As a
result of genetic alterations or environmental influences, the insulin-producing cells – the
beta cells in the pancreas – are destroyed. Often children and adolescents are affected.
When approximately 80 percent of these cells have failed, there is a dramatic rise in
blood glucose levels leading to the outbreak of the disease. Without insulin treatment,
the outcome of the disease would be fatal.
Trial coordinator of the
diabetes trials INIT II and
TEENDIAB and research
associate at the Institute of
Zentrum München
The physician Ruth Chmiel and the biologist Florian Haupt are working at the Institute
of Diabetes Research to develop a vaccine against the dangerous disease. “By detecting certain antibodies in the blood we can diagnose the dysregulation of the immune
system, which ultimately leads to the outbreak of the disease, at an early stage,” said
Ruth Chmiel. “Practically all individuals in whom two or more of these antibodies
have been detected develop type 1 diabetes within 15 to 20 years after diagnosis. If
detected early, there is still time for preventive immunotherapy.”
2011:
PhD degree, V
isiting Scientist,
SYKE Finnish Environment
Institute, Helsinki
Within the framework of the Intranasal Insulin Trial (INIT II) and the Oral Insulin Trial,
the two scientists select appropriate German candidates who can participate in the
trial of such a vaccine. Whoever has close relatives with type 1 diabetes and in whose
blood the characteristic autoantibodies can be detected can take part in the trial.
The subjects take one capsule with insulin daily or are treated with intranasal insulin
spray once a week. “The immune system of the body can thus gradually get used to
the insulin,” explained Chmiel. “It acts directly on the nasal mucosa and in this way
does not disturb the metabolism.”
First successes of the vaccine have already been confirmed: Evaluations of a trial in
the U.S. have shown that through the oral administration of insulin in young children
and in individuals with high autoantibody titers, the onset of diabetes can be delayed
significantly.
The trials in Munich will be accompanied by projects that address fundamental questions.
“In translational projects at Helmholtz Zentrum München, we are studying how changes
in the metabolism affect the development of type 1 diabetes,“ said Florian Haupt. “In
addition, cells of the immune system are being analyzed to elucidate the underlying
disease processes.” Helmholtz Zentrum München is now right at the interface of basic
research and the translation of the findings into medical practice. The Institute of Diabetes
Research is, so-to-speak, the spearhead of diabetes research in Germany.
2011-2012:
Research associate,
2009-2011:
Case Manager for Vascular
Surgery, Kliniken Südostbayern,
Klinikum Traunstein
BRIEF PROFILE
RUTH CHMIEL
Trial physician and research
associate at the Institute of
Zentrum München
2009-2012:
Dissertation, Institute of
Zentrum München and
Research Group Diabetes,
Klinikum rechts der Isar, Technische Universität München
Publications:
Stefanie Krause et al.: IA-2
Autoantibody Affinity in Children
at Risk for Type 1 Diabetes.
Clinical Immunology 145
(2012) 224–229 | doi: 10.1016/j.
clim.2012.09.010
The physician Ruth Chmiel and the biologist Florian Haupt explore new avenues for
the prevention of type 1 diabetes. Through the oral and intranasal administration of
insulin (in the image: insulin crystals) they are seeking to delay the onset of type 1
diabetes in risk patients.
Jennifer Raab et al.: Continuous
Rise of Insulin Resistance
Before and After the Onset of
Puberty in Children at Increased
Risk for Type 1 Diabetes – a
Cross-Sectional Analysis.
Diabetes Metab Res Rev.
29(2013)631-635 | doi: 10.1002/
dmrr.2438
Talent Management
TA RG E T G RO U P S
Talented scientists and outstanding staff are elemental to the success of
Helmholtz Zentrum München. Excellent researchers and competent staff in
science management and in the administration and technical infrastructure
require a strategic human resources management. This includes human
resources development which is systematically oriented on the needs of
various target groups and on the Center’s strategy.
The focus of Human Resources Development at
Helmholtz Zentrum München is on the promotion of young scientists and high potentials,
especially in the areas of professional, methodological, social and leadership skills.
It is complemented by a wide range of continuing
education and training courses. Both levels take
into account the increasing complexity of today’s
research, which takes place in an international
environment in cross-linked infrastructures.
In 2012 and 2013, human resources development
activities at the Center increased dynamically
due to the consistent orientation towards needs
and demand. More than 150 internal training
events are held per year. Besides scientific topics,
language and computer courses and training in
management and social skills are predominant.
Furthermore, in the past two years, more than
70 moderated team workshops were held under
supervision of Human Resources Development.
The workshops mainly focused on leadership
and cooperation topics as well as changes in
processes, structures, roles and responsibilities.
The team approach was also applied to specific
training topics that have to be implemented
in and adjusted to particular organizational
units, such as project and time management
or systematic personnel selection. Individual
training courses and support for managers and
potential executives were also expanded. In this
context the implementation of an internal developmental program for managers and management trainees plays an important role.
Based on individual advisory consultations,
external training programs are also offered
and arranged. For the qualification of science
managers and administrators the training
program of the Center for Science Management
(ZWM) in Speyer and the Helmholtz Management Academy are especially suitable.
Coaching and differentiated mentoring programs
supplement the portfolio of effective development measures. These include – in addition
to the individual support provided by Human
Resources Development – offers of the Helmholtz
Association such as the mentoring program
for young women in science, the shadowing
program for employees in the administrativetechnical area and a cross-company mentoring
program in the Munich region.
Team
workshops
Continuing
education and
training
Individual
qualifying
measures
HUMAN RESOURCES
DEVELOPMENT
Mentoring
STR
AT E G
Training
programs
Coaching
U
Y FOR THE FUT
RE
Continuing
Education and
Training
3400
participants in seminars
and training courses
As examples, we present two participants in the “Munich Leadership Development in
Science” program, which Helmholtz Zentrum München helped to initiate.
TALENT MANAGEMENT
TALENT MANAGEMENT
112 113 Recruiting and
Promoting Talent in
Science Administration
BRIEF PROFILE
BARBARA FERWAGNER
Barbara Ferwagner is project
coordinator in the Department
of Operations & Support. From
2011 to the beginning of 2014
she was assistant to the CFO.
She came to Helmholtz Zentrum
München in 2004, where she
first was financial and project
management assistant at the
Institute of Experimental Genetics. Barbara Ferwagner studied
business engineering at the
University of Applied Sciences
Munich.
BRIEF PROFILE
THERESIA SCHMITT
Theresia Schmitt has worked
since 2011 as project coordinator in the Department
of O
perations & Support.
Prior to that she worked for
three years as a business
consultant. Theresia Schmitt
studied business administration at Ludwig-Maximilians-
Universität München and spent
one semester at the Università
Commerciale Luigi Bocconi in
Milan.
“Professionalism, leadership and management skills as
well as social competence are the four important qualities
that characterize good science managers.” Uwe Bott
Science is not created in a vacuum, quite the contrary: Funds have to be
acquired and managed; laboratories must be operated and services
organized; scientists and specialists in various fields have to be recruited
and hired. Only if the framework conditions are suitable, can researchers
utilize their capabilities in an optimal way. That is why efficient management is
needed. “In a research center such as ours, the administration must navigate
between world-class science with high dynamics on the one hand and the
relatively rigid requirements of the public service sector on the other,” said
Uwe Bott, who heads Human Resources Development at Helmholtz Zentrum
München. Both sides have to be taken into account: the researchers who want
to remain as flexible as possible and who want to avoid spending too much
time on administrative tasks, and the administrators who often must comply
with rigid official structures and who are not particularly well paid.
However, to be successful in international competition, new processes and structures must
be developed, and there is a special need for
science managers who are keen in solving very
specific problems in this area. “At Helmholtz
Zentrum München we have established a number
of options in which employees can take part
in continuing education and training courses
and develop further in this area,” said Bott.
“We offer around 150 Center-internal training
events, which in part are intensive courses on
management topics such as scientific project
management. There are also seminars and
workshops in which employees acquire specific
knowledge and skills and practice the transfer of
learning objectives into daily work. Our center
also participates in the Helmholtz Management
Academy, whose purpose is to promote under
standing between science and the administration.
In addition, we have intensified our cooperation
with the Center for Science Management (ZWM)
Speyer; since October, five of our employees
have been participating in the one-year
program ‘Munich Leadership Development in
Science’. It is aimed at academic and administrative leaders from universities and research
institutions in the Munich region, who already
have or will soon have budget and staff responsibility.”
One of the participants of the course, Barbara
Ferwagner, has been working since March in the
Department of Operations & Support. In her previous positions at Helmholtz Zentrum München
she was able to gain experience in a number of
different areas. “In order to qualify for leader
ship roles, it is necessary to step out once from
the microcosm of one’s own center and to
discuss similar issues with colleagues from other
academic institutions,” she said. “There are so
many different cultures and ways of organizing
science administration. This exchange with other
colleagues represents a great added value of the
program.” In principle, the challenges are always
the same: leading people, managing resources,
developing strategies, communicating and
implementing, balancing interests, organizing
majorities, making and carrying out decisions.
The day to day work requires from leaders a wide
range of management skills and the ability to
relate these to the special characteristics of science management. The ZWM program therefore
offers modules on leadership and self-leadership,
project management, budgeting, and employee
motivation, among other topics. Barbara
Ferwagner finds the concept of the course convincing, since the basic principles of a variety of
skills are taught.
In addition to the qualification in management
responsibilities, her colleague Theresia
Schmitt, who has been working as project
coordinator since 2011 in the Department of
Operations and Support, sees a significant
added value of the ZWM program in building
networks at the science location Munich. Her
supervisor recommended her for the program
and – just as for Barbara Ferwagner – Helmholtz Zentrum München assumes the costs; the
participants themselves must devote the necessary time by means of holidays or flextime.
The thirty-two year-old business graduate with
a specialization in health economics likes the
interdisciplinary work: “In science management
at our center many aspects intertwine: business
administration, medical and legal topics as well
as topics of company consulting such as process
optimization or organizational structures. That
is exciting and varied. Every day you can deal
with something new, which is why the training
course must cover many aspects.” Her goal is
to make it as easy as possible for the scientists
and to largely relieve them of administrative
duties. “We are establishing a new adminis
trative structure at Helmholtz Zentrum
München for this purpose to ensure that each
institute has a primary contact person who
coordinates all the further details.”
Uwe Bott underlines how important it is to
have transparent processes and to avoid
having different people responsible for the
same topics. “That is why good science
managers are so essential,” he said. “The four
aspects – professionalism, leadership and
management skills as well as social competence – must be covered already in the training
phase. Once this requirement profile is clearly
defined, it is easier to select the appropriate
executives and to give them systematic training.”
BRIEF PROFILE
DR. UWE BOTT
Dr. Uwe Bott heads the Department of Human Resources
Development at Helmholtz
Zentrum München. He studied
education, psychology and
sports science at the University of Düsseldorf, completed
his doctorate and worked
and conducted research in
the treatment and training of
chronically ill patients. From
1999 to 2011 Uwe Bott was
responsible for Human
Resources Development at
the German Aerospace
Center (DLR).
Facts
& Figures
2012/2013
2234
employees
More than three fourths of the employees are science staff. The proportion of women in
leadership positions is 51 percent at the research group and junior research group level.
FACTS & FIGURES 2012/2013
116 117 Staff
Scientists’ disciplines
Biology
Mathematics
1 %
Helmholtz Zentrum München is an attractive employer for a broad spectrum
of science-oriented professions. The Center’s dynamic development and
its international work environment make it an interesting place to work
both for renowned researchers and for novice scientists and administrators.
In 2012, Helmholtz Zentrum München employed
a total of 2148 people from 65 different countries.
In 2013 the number of employees increased to
2234; the percentage of employees financed via
third-party funding dropped from 29 percent to
25 percent. Over three quarters of the staff work
in the scientific area; in 2012 these included 330
doctoral students, 186 postdocs and 503 scientists. In 2013 the scientific staff was made up
of 328 doctoral students, 200 postdocs and 535
scientists. Research activities focus on the areas
of biology, biochemistry, physics and medicine.
Equal Opportunities
Helmholtz Zentrum München views equal opportunities for men and women to be an integral part
of its corporate culture. It promotes the careers of
women employees and creates equal framework
conditions for professional success. To improve
the compatibility of work and family both for
men and women in equal measure, child care
options for employees' children on the research
campus are continually being expanded.
In 2012 and 2013 women made up 59 percent of
the workforce. The overall proportion of women
in leadership positions is 34 percent; 51 percent
of the research groups and junior research
groups are headed by women.
Vocational Training
In addition to the promotion of young scientists,
Helmholtz Zentrum München is engaged in
vocational training and offers a broad spectrum
of vocational training disciplines. At the end
of 2012 there were 61 vocational trainees; at the
end of 2013 there were 63 trainees in commercial and technical vocations as well as future
animal keepers.
Women in Leadership Positions
2 %
3 %
Agricultural Science/
Forestry
8 %
Percentage of women
as leaders of research
groups or junior
research groups
34 %
66 %
Epidemiology/Health
Science
40 %
Geology/
Environmental Science
8 %
Engineering
15 %
Physics/Biophysics
Chemistry/Biochemistry
No MINT Subjects
15 %
8 %
1 %
6 %
Medicine
Veterinary Medicine
Other
Disciplines
Distribution of staff by area of work
76 %
Percentage of women
in leadership
positions
Computer Science
4 % 4 %
13 %
51 % 49 %
13 %
11 %
Science
Infrastructure
Administration
As of: December 31, 2013
118 119 Finances 2012
In 2012, the overall budget of Helmholtz Zentrum München amounted to
approximately 211 million euros, with 165 million euros coming from
institutional funding provided by the Federal Government and the Free State
of Bavaria at a ratio of 90:10. External funds from national and international
research grants amounted to 45.9 million euros, including the funds that
were forwarded to third parties.
Institutional funding 2012
15.1
million
euros
16.5 million
euros
21.8 million
euros
Personnel costs
Material costs
69.1
million
euros
Costs for third-party
subsidies
Ongoing
investments
42.8
million
euros
Total financing and funding sources 2012
Construction and
procurements
> 2.5 million euros
External funding according to source 2012
0.8 million euros
Institutional funds from
the Federal Government
Institutional
funds from the Free
State of Bavaria
Third-party funds
5.3
million
euros
45.9
million
euros
16.5 million
euros
6.7 million
euros
148.8
million
euros
Federal Government
project funding
State Government
project funding
12.0
million
euros
German Research
Foundation (DFG)
Helmholtz Association
Other national sources
9.0 million
euros
4.3 million
euros
4.8 million
euros
0.6 million euros
Federal bureaus
EU
Funds forwarded
Industry (international)
0.4 million euros
2.0 million euros
Contract research
120 121 Finances 2013
In 2013, the overall budget of Helmholtz Zentrum München amounted to
approximately 224 million euros, with 172 million euros coming from
institutional funding provided by the Federal Government and the Free State
of Bavaria at a ratio of 90:10. External funds from national and international
research grants amounted to 51.7 million euros, including the funds that
were forwarded to third parties.
Institutional funding 2013
11.4
million
euros
15.0
million
euros
Personnel costs
75.8
million
euros
23.2 million
euros
Material costs
Costs for third-party
subsidies
Ongoing
investments
46.8
million
euros
Total financing and funding sources 2013
Construction and
procurements
> 2.5 million euros
External funding according to source 2013
Federal Government
project funding
1.1 million euros
Institutional funds from
the Federal Government
Institutional
funds from the Free
State of Bavaria
Third-party funds
0.8 million euros
6.7 million
euros
51.7
million
euros
17.2 million
euros
155.0
million
euros
State Government
project funding
10.0
million
euros
0.7 million euros
Helmholtz Association
3.5 million
euros
12.6
million
euros
German Research
Foundation (DFG)
Other national sources
Federal bureaus
5.4 million
euros
EU
Funds forwarded
8.3 million
euros
Industry (international)
2.0 million euros
0.6 million euros
Contract research
Business operations
122 123 Project Funding and
Research Cooperations
Helmholtz Zentrum München successfully takes part in in calls for proposals
by the Federal Ministry of Education and Research, the European R
esearch
Framework Programme, the German Research Foundation (DFG), the
Helmholtz Association of German Research Centres and other public and
private o rganizations. In 2012 the acquired third-party funding amounted
to 39.2 million euros, and in 2013 the amount was 39.1 million euros.
In public funding for Helmholtz Zentrum
München, the Federal Government ranks first
with approximately 12 million euros per year,
followed by the European Union with almost
9 million euros and the German Research
Foundation (DFG) with more than 4 million euros.
At the end of 2013 there were more than 350
third-party agreements for research funding.
By the end of 2013, Helmholtz Zentrum München
contributed to almost 430 proposals in the 7th
Research Framework Programme of the European Union. This resulted in 113 projects with
approximately 63 million euros in funds from the
EU for the Center.
Helmholtz Zentrum München was particularly
successful in acquiring grants from the European
Research Council (ERC). The Center has a total
of 12 ERC grantees with a funding volume of
15.9 million euros and thus assumes a leading
position among the Helmholtz Centres.
Researchers at the Center who apply for grants
receive intensive coaching and support from
staff members of the Department of Program
Planning and Management.
While the average success rate for Starting
Grants and Consolidator Grants is 13.9 percent
in the EU, Helmholtz Zentrum München received
nine grants for a total of 34 proposals – a
success rate of 26.5 percent.
ERC Grants at Helmholtz Zentrum München
Number
Funding [in millions of euros]
Starting Grants
[brought to the Center]
7
1
9.02
0.53
Consolidator Grants
2
3.85
Advanced Grants
[as cooperation partner]
1
1
2.38
0.08
Total:
12
15.9
In 2013 Dr. Martin Elsner and Dr. Tillmann
Lüders each received an ERC Consolidator
Grant. The two research group leaders at the
Institute of Groundwater Ecology are to receive
a total of 3.85 million euros funded by the
European Research Council for their research.
Prof. Dr. Magdalena Götz, director of the
Institute of Stem Cell Research and Chair of
Physiological Genomics at Ludwig-Maximilians-Universität, received an ERC Advanced
Grant endowed with 2.38 million euros for her
research on molecular mechanisms regulating
neurogenesis. The grant for Magdalena Götz
is one of the few Advanced Grants awarded
to German women researchers in 2013: From
2400 submitted project proposals, 37 male
and only 4 female Principal Investigators from
Germany were awarded a grant.
Scientists of Helmholtz Zentrum München were
extraordinarily successful in the last call for
proposals on the topic of Health within the 7th
Research Framework Programme. From nine
proposals submitted by the Center in the second
phase, six projects were approved with a total
funding volume of more than 3 million euros.
For his contributions to German-French
cooperation in the field of pneumology, Oliver
Eickelberg was awarded the Gay Lussac-Humboldt Research Award 2013. Under his leadership, the Helmholtz-INSERM-Alliance for the
Cure of Chronic Lung Disease was founded,
which evolved from an initiative of the research
ministries of both countries.
Through its participation in programs of the
Federal Ministry of Education and Research
(BMBF), Helmholtz Zentrum München makes
significant contributions to current issues of
great social and economic importance. The
Center was thus able to solicit considerable
research funds in 2012 and 2013. Particularly
noteworthy are the German Plant Phenotyping
Network (DPPN) with 6.1 million euros in funding and two competence networks on radiation
research coordinated by the Center, together
amounting to 2.1 million euros.
The BMBF research network on photonics
“Ultrasensitive detection and manipulation
of cells and/or tissues and their molecular
components” is coordinated by Helmholtz
Zentrum München. From the BMBF funding
initiative “e:Med – Measures to Establish Systems
Medicine” the Center receives 2.0 million euros
for its research contributions on heart attack,
stomach cancer, neurodegeneration and alcohol
addiction. Within the framework of the 2nd funding phase of the BMBF Competence Networks on
Obesity and Diabetes, the Center receives a total
of 0.8 million euros in funds. The German Center
for Infectious Disease Research (DZIF) forwards
2.7 million euros in funding to Helmholtz
Zentrum München for its research projects.
Significant projects supported by research
foundations include the Max Eder Junior
Research Group “Therapeutic Inhibition of Autocrine Signals in Breast Cancer Stem Cells” led by
Dr. Christina Scheel, which is funded by the
German Cancer Aid with 0.7 million euros, and a
network on Parkinson research coordinated by
the Center, which is led by Dr. Christian Johannes
Gloeckner; this network is funded by the Michael
J. Fox-Foundation with 0.5 million U.S. dollars.
124 125 In 2012 and 2013 a total of 20 new projects were approved
by the Initiative and Networking Fund (IVF) of the Helmholtz
Association of German Research Centres:
The Helmholtz Alliance ICEMED (Imaging and Curing Environmental Metabolic Diseases), coor
dinated by Prof. Dr. Matthias Tschöp and including 18 partners, is being funded with a total
of 15 million euros until 2017. Of these funds, four million euros are to remain at Helmholtz
Zentrum München.
Helmholtz Zentrum München has close contacts
with the two Munich universities and the
Max Planck Institutes of Biochemistry and of
Neurobiology. The success of this cooperation is
shown in nine Collaborative Research Centres/
Transregios of the German Research Foundation
(DFG), in which Helmholtz Zentrum München
participates with 34 subprojects. Along with
Berlin, Munich plays a prominent role as cluster
location for the life sciences in Germany.
The Center is a partner in the Helmholtz Alliance Preclinical Comprehensive Cancer Center
(PCCC), in the Helmholtz Alliance Remote Sensing and Earth System Dynamics and the special
project Synthetic Biology, altogether funded with 0.8 million euros.
For Helmholtz Zentrum München, projects
funded by the German Research Foundation
comprise an important component of the
externally funded research activities. This
especially applies to young, outstanding junior
research group leaders, who are funded
through the Emmy Noether Program of the
DFG. In 2012/2013 the Center established three
new junior research groups with a total volume
of more than 4.5 million euros through this
funding program.
Participation of Helmholtz Zentrum München in
DFG-funded projects 2012/2013
The Helmholtz Research School of Radiation Sciences (RS2) receives funding amounting to
1.8 million euros.
Funding program
Projects
7 Collaborative Research Centres and 2 Transregios
34
In the framework of the Helmholtz Postdoctoral Program, three projects are to receive 100 000
euros each over three years, and two additional projects from the research field Health are to
receive 150 000 euros each.
10 priority programs
13
7 research groups
7
Within the framework of the W2/W3 program for women professors, Dr. Irmela Jeremias has
received a W2 position to conduct research on “Diseases of the Immune System – Personalized
Medicine Targeting Leukemia Stem Cells”.
Leibniz Prize
1
Junior research groups in the Emmy Noether Program
3
Two Helmholtz International Research Groups at the Institute of Diabetes Research and the
Institute of Lung Biology are being funded with 280 000 euros.
Individual grants
39
Four new Helmholtz Young Investigator Groups are to receive 625 000 euros each over five
years.
As part of the Helmholtz-Alberta Initiative “Infectious Diseases Research”, the Institute of
Virology under the direction of Prof. Dr. Ulrike Protzer has been awarded 0.2 million euros for
research projects.
Two of the Helmholtz International Fellow Awards, which are endowed with 20 000 euros
each and were awarded for the first time in 2013, went to cooperation partners of Helmholtz
Zentrum München: Prof. Dr. Harald von Boehmer of Harvard Medical School in Boston, and
Prof. Dr. Naftali Kaminski of the University of Pittsburgh.
Dr. Jan Krumsiek, Institute of Computational Biology, has received the Helmholtz Doctoral
Student Award in the research field Health, which is endowed with 5000 euros.
International Cooperation
In 2012/2013, Helmholtz Zentrum München
participated in approximately 1200 international scientific collaborations with universities,
non-university research institutions and industry partners in over 60 countries.
These partnerships may, but need not necessarily have a contractual basis. In 2013, there were
more than 270 cases of international funding or
cooperation agreements, often with multiple
partners.
International cooperation serves the exchange
between scientists on the basis of guest stays
and collaborative research or publications.
The U.S. tops the list by far in the number of
non-European cooperative projects, followed by
Canada, China and Japan. Within Europe, Center
scientists collaborate particularly often with
scientists from the UK, France, Italy, Austria, the
Netherlands, Switzerland and Spain.
A special element of the Center’s international
activities is the Helmholtz-Israel cooperation
on personalized medicine, which was launched
in 2013 and in which Helmholtz Zentrum
München and four other biomedical Helmholtz
centers and scientific institutions in Israel have
joined together. The objective of the long-term
cooperation is to develop new strategies for
personalized medicine in the field of diagnosis,
treatment and prevention of widespread common
diseases such as diabetes.
Organization
39
Scientific Institutes and
Research Units
In the fields of Environmental and Radiation Sciences, eleven institutes and research units have
joined to form departments; five institutes comprise the Helmholtz Diabetes Center.
ORGANIZAT ION
ORGANIZAT ION
128 129 Institutes and Research Units
TOPIC 1
Systemic Analysis of Genetic and Environmental Factors with an Impact on Health
INSTITUTE OF EPIDEMIOLOGY II
(EPI II)
INSTITUTE OF EXPERIMENTAL
GENETICS (IEG)
INSTITUTE OF HUMAN GENETICS
(IHG)
Director: Prof. Dr. Annette Peters
[email protected]
T 089 3187 4566
– also Topic 2 –
Director: Prof. Dr. Martin Hrabe de
Angelis
[email protected]
T 089 3187 3502
Chair of Experimental Genetics at
TUM
Director: Prof. Dr. Thomas Meitinger
[email protected]
T 089 3187 3294
Chair of Human Genetics at TUM
INSTITUTE OF GENETIC
EPIDEMIOLOGY (IGE)
Director: Prof. Dr. Konstantin Strauch
[email protected]
T 089 3187 2838
Chair of Genetic Epidemiology at LMU
RESEARCH UNIT MOLECULAR
EPIDEMIOLOGY (AME)
GENOME ANALYSIS CENTER (GAC)
Service platform
Head: Prof. Dr. Jerzy Adamski
[email protected]
T 089 3187 3155
INSTITUTE OF DEVELOPMENTAL
GENETICS (IDG)
– also Topic 4 –
Director: Prof. Dr. Wolfgang Wurst
[email protected]
T 089 3187 4110
Chair of Developmental Genetics at
TUM
RESEARCH UNIT COMPARATIVE
MEDICINE (AVM)
Head: Dr. Christian Gieger
christian.gieger@
T 089 3187 4106
Head: PD Dr. Markus Brielmeier
[email protected]
T 089 3187 2837
INSTITUTE OF EPIDEMIOLOGY (EPI I)
INSTITUTE OF LUNG BIOLOGY (iLBD)
Director (acting): Dr. Joachim
Heinrich
[email protected]
T 089 3187 4150
Director: Prof. Dr. Oliver Eickelberg
oliver.eickelberg@
T 089 3187 4666
Chair of Experimental Pneumology
at LMU
Diabetes: Pathophysiology, Prevention and Therapy
HELMHOLTZ DIABETES CENTER (HDC)
INSTITUTE FOR DIABETES AND
OBESITY (IDO)
Speaker: Prof. Dr. Matthias Tschöp
INSTITUTE OF DIABETES
RESEARCH (IDF)
Director: Prof. Dr. Anette-Gabriele
Ziegler
anette-g.ziegler@
T 089 3187 3405
Chair of Diabetes and Gestational
Diabetes at TUM
Director: Prof. Dr. Matthias Tschöp
matthias.tschoep@
T 089 3187 2103
Chair of Metabolic Diseases at TUM
INSTITUTE OF DIABETES AND
REGENERATION RESEARCH (IDR)
Director: Prof. Dr. Heiko Lickert
[email protected]
T 089 3187 3760
Chair of Diabetes Research/Beta Cell
Biology at TUM
INSTITUTE OF DIABETES RESEARCH
AND METABOLIC DISEASES OF
HELMHOLTZ ZENTRUM MÜNCHEN AT
THE UNIVERSITY OF TÜBINGEN (IDM)
Director: Prof. Dr. Hans-Ulrich Häring
hans-ulrich.haering@
med.uni-tuebingen.de
T 07071 298 2735
Medical Director, University Hospital
Tübingen, Medical Department IV
INSTITUTE OF ALLERGY RESEARCH
(IAF)
Director: Prof. Dr. Carsten
Schmidt-Weber
schmidt-weber@
T 089 3187 3081
Chair of Molecular Allergology and
Environmental Research at TUM
Mechanisms of Genetic and Environmental Influences on Health and Diseases
INSTITUTE OF STEM CELL
RESEARCH (ISF)
RESEARCH UNIT CELLULAR SIGNAL
INTEGRATION (AZS)
Director: Prof. Dr. Magdalena Götz
magdalena.goetz@
T 089 3187 3750
Chair of Physiological Genomics
at LMU
Head: Prof. Dr. Daniel Krappmann
daniel.krappmann@
T 089 3187 3461
RESEARCH UNIT SENSORY BIOLOGY
AND ORGANOGENESIS (SBO)
Head: Dr. Hernan Lopez-Schier
hernan.lopez-schier@
T 089 3187 2187
INSTITUTE OF PATHOLOGY (PATH)
TOPIC 2
TOPIC 3
Chronic Lung Diseases and Allergies
Director: Prof. Dr. Heinz Höfler
[email protected]
T 089 4140 4161
Chair of General Pathology and
Pathological Anatomy at TUM
RESEARCH UNIT ANALYTICAL
PATHOLOGY (AAP)
INSTITUTE OF CLINICAL MOLECULAR
BIOLOGY AND TUMOR GENETICS
(KMOLBI)
Director (acting): Prof. Dr. Wolfgang
Hammerschmidt
hammerschmidt@
T 089 3187 1506
EPIGENETICS (MEG)
Head: Prof. Dr. Dirk Eick
[email protected]
T 089 3187 1512
INSTITUTE OF MOLECULAR
IMMUNOLOGY (IMI)
Head: Prof. Dr. Axel Karl Walch
[email protected]
T 089 3187 2739
Director (acting):
Prof. Dr. Ralph Mocikat
[email protected]
T 089 3187 1301
INSTITUTE OF MOLECULAR TOXICOLOGY AND PHARMACOLOGY (TOXI)
IMMUNE REGULATION (AMIR)
Director: Prof. Dr. Martin Göttlicher
martin.goettlicher@
T 089 3187 2446
Chair of Toxicology and
Environmental Hygiene at TUM
Head: Dr. Vigo Heissmeyer
vigo.heissmeyer@
T 089 3187 1214
INSTITUTE OF VIROLOGY (VIRO)
Director: Prof. Dr. Ulrike Protzer
[email protected]
T 089 3187 3004
Chair of Virology at TUM
RESEARCH UNIT GENE VECTORS
(AGV)
Head: Prof. Dr. Wolfgang Hammerschmidt
hammerschmidt@
T 089 3187 1506
DEPARTMENT OF RADIATION SCIENCES
Speaker: Dr. Peter Jacob
RESEARCH UNIT MEDICAL RADIATION
PHYSICS AND DIAGNOSTICS (AMSD)
Head: Prof. Dr. Christoph Hoeschen
christoph.hoeschen@
T 089 3187 4560
INSTITUTE OF RADIATION BIOLOGY (ISB)
Director: Prof. Dr. Michael Atkinson
[email protected]
T 089 3187 2983
Chair of Radiation Biology at TUM
INSTITUTE OF RADIATION
PROTECTION (ISS)
Director (acting): Dr. Peter Jacob
[email protected]
T 089 3187 4020
RESEARCH UNIT RADIATION
CYTOGENETICS (ZYTO)
Head: Prof. Dr. Horst Zitzelsberger
[email protected]
T 089 3187 3421
TOPIC 4
ORGANIZAT ION
ORGANIZAT ION
130 131 Institutes and Research Units
TOPIC 5
New Technologies for Biomedical Discoveries
INSTITUTE OF STRUCTURAL BIOLOGY
(STB)
Director: Prof. Dr. Michael Sattler
[email protected]
T 089 289 13867
Chair of Biomolecular NMR-Spectroscopy at TUM
INSTITUTE OF BIOLOGICAL AND
MEDICAL IMAGING (IBMI)
Director: Prof. Dr. Vasilis Ntziachristos
v.ntziachristos@
T 089 3187 3852
Chair of Biological Imaging at TUM
Chair of Genome-oriented Bioinformatics at TUM
RESEARCH UNIT SCIENTIFIC
COMPUTING (ASC)
RESEARCH UNIT PLANT GENOME
AND SYSTEMS BIOLOGY (PGSB)
Head: PD Dr. Wolfgang Graf zu CastellRüdenhausen
[email protected]
T 089 3187 2946
Head: Dr. Klaus Mayer
[email protected]
T 089 3187 3584
INSTITUTE OF COMPUTATIONAL
BIOLOGY (ICB)
Director: Prof. Dr. Dr. Fabian Theis
[email protected]
T 089 3187 4159
Chair of Mathematical Modeling of
Biological Systems at TUM
INSTITUTE OF HEALTH ECONOMICS
AND HEALTH CARE MANAGEMENT
(IGM)
Director: Prof. Dr. Reiner Leidl
[email protected]
T 089 3187 4168
Chair of Health Economics and Health
Care Management at LMU
INSTITUTE OF BIOINFORMATICS AND
SYSTEMS BIOLOGY (IBIS)
DEPARTMENT OF PROTEIN ANALYTICS
(PROT)
Director: Prof. Dr. Hans-Werner Mewes
[email protected]
089 3187 3580
Head: Prof. Dr. Marius Ueffing
marius.ueffing@
T 089 3187 3567
Helmholtz Research Program Terrestrial Environment
Translational Centers and Clinical Cooperation Groups
TREATMENT CENTER FOR DIABETES
PREVENTION STUDIES
Head: Prof. Dr. Anette-Gabriele
Ziegler
anette-g.ziegler@
T 089 3187 3405
COMPREHENSIVE PNEUMOLOGY
CENTER (CPC)
Scientific Director: Prof. Dr. Oliver
Eickelberg
oliver.eickelberg@
T 089 3187 4666
Institute of Lung Biology; Clinical
partners: University Hospital M
unich,
Asklepios Specialist Hospital,
Munich-Gauting
MUNICH ALLERGY RESEARCH
CENTER (MARC)
Head: Prof. Dr. Carsten
Schmidt-Weber
schmidt-weber@
089 4140 3081
Institute of Allergy Research;
Clinical partners: Dept. of
Dermatology and Allergology at TUM,
ZAUM – Center for Allergy and Environment
DEPARTMENT OF ENVIRONMENTAL
SCIENCES (DES)
COOPERATION GROUP COMPREHENSIVE MOLECULAR ANALYTICS (CMA)
RESEARCH UNIT MICROBE-PLANT
INTERACTIONS (AMP)
CLINICAL COOPERATION GROUPS
DIABETES
Speaker: Prof. Dr. Jörg Durner
Head: Prof. Dr. Ralf Zimmermann
ralf.zimmermann@
T 089 3187 4544
Head: Prof. Dr. Anton Hartmann
anton.hartmann@
T 089 3187 4109
INSTITUTE OF SOIL ECOLOGY
RESEARCH UNIT ANALYTICAL BIOGEOCHEMISTRY (BGC)
Subclassification of Type 2 Diabetes
and Risk Estimation by Metabolic and
Genetic Marker Profiles
Head: Prof. Dr. Jochen Seißler
jochen.seissler@
T 089 3187 3502
Institute of Experimental Genetics;
Clinical partners: University Hospital
Munich, City Campus
INSTITUTE OF BIOCHEMICAL
PLANT PATHOLOGY (BIOP)
Director: Prof. Dr. Jörg Durner
[email protected]
T 089 3187 3434
Chair of Biochemical Plant
Pathology at TUM
Director: Prof. Dr. Jean Charles Munch
[email protected]
T 089 3187 4064
Chair of Soil Ecology at TUM
RESEARCH UNIT ENVIRONMENTAL
SIMULATION (EUS)
INSTITUTE OF GROUNDWATER
ECOLOGY (IGOE)
Head: Prof. Dr. Jörg-Peter Schnitzler
[email protected]
T 089 3187 2413
Director: Prof. Dr. Rainer Meckenstock
rainer.meckenstock@
T 089 3187 2561
Chair of Groundwater Ecology at TUM
Head: PD Dr. Philippe
Schmitt-Kopplin
schmitt-kopplin@
T 089 3187 3246
RESEARCH UNIT ENVIRONMENTAL
GENOMICS (EGEN)
Head: Prof. Dr. Michael Schloter
[email protected]
T 089 3187 2304
Interaction of Diet and Genetics in
Type 2 Diabetes Mellitus
Leitung: Prof. Dr. Hans Hauner
[email protected]
T 089 3187 3502
Institute of Experimental Genetics;
Clinical partner: Else-KrönerFresenius Center for Nutritional
Medicine, TUM
PATHOMECHANISMS AND
THERAPEUTIC TARGETS
Pathogenesis of Acute Myeloid
Leukemia
Head: Prof. Dr. Wolfgang
Hiddemann
wolfgang.hiddemann@
T 089 7095 2551
Institute of Clinical Molecular Biology
and Tumor Genetics; Clinical partner:
Dept. of Internal Medicine III at LMU;
University Hospital Munich, Grosshadern Campus
Osteosarcoma
Head: PD Dr. Michaela Nathrath
michaela.nathrath@
T 089 3187 2312
Institute of Pathology; Clinical partner:
Children's Hospital and Polyclinic for
Children's and Youth Medicine, TUM
Klinikum Schwabing StKM GmbH
INNOVATIVE THERAPIES
Pediatric Tumor Immunology
Head: Prof. Dr. Uta Behrends
uta.behrends@
T 089 3068 3076
Institute of Clinical Molecular Biology
and Tumor Genetics; Clinical partner:
Children's Hospital and Polyclinic for
Children's and Youth Medicine,TUM
Klinikum Schwabing StKM GmbH
Antigen-Specific Immunotherapy
Head: Prof. Dr. Dirk Busch
[email protected]
T 089 4140 4120
nstitute of Virology;
Clinical partner: Institute of Medical
Microbiology, Immunology and
Hygiene at TUM
Innate Immunity in Tumor Biology
Head: Prof. Dr. Gabriele Multhoff
gabriele.multhoff@
T 089 4140 4514
Institute of Pathology; Clinical partner:
Department of Radiotherapy and
Radiooncology at TUM
Immune Oncology
Head: Dr. Andreas Moosmann
andreas.moosmann@
T 089 3187 1231
Research Unit Gene Vectors, Clinical
partner: Dept. of Internal Medicine III
of LMU; University Hospital Munich,
Grosshadern Campus
Immunotherapy
Head: PD Dr. Marion Subklewe
marion.subklewe@
T 089 3187 1412
Institute of Molecular Immunology;
Clinical partner: Dept. of Internal
Medicine III of LMU; University Hospital Munich, Grosshadern Campus
Personalized Radiotherapy
Head: Dr. Anna Friedl
[email protected]
T 089 3187 2447
Research Unit Radiation Cytogenetics;
Clinical partner: Dept. of Radiation
Therapy and Radiooncology of LMU;
University Hospital Munich
Platform Immune Monitoring
Head: Prof. Dr. Dolores Schendel
[email protected]
T 089 3187 1301
Institute of Molecular Immunology;
Clinical partner: Dept. of Internal
Medicine III of LMU; University Hospital Munich, Grosshadern Campus
ORGANIZAT ION
132 Organization
Helmholtz Zentrum München is a research institution of the Federal
Government and the Free State of Bavaria. The partners are the Federal
Republic of Germany, represented by the Federal Minister of Education and
Research, and the Free State of Bavaria, represented by the Bavarian State
Minister of Finance, Regional Development and Regional Identity.
The bodies of the company are the Assembly of Partners, the Supervisory Board
and the Board of Directors. The Scientific Advisory Board, which is made
up of external members, advises Helmholtz Zentrum München on scientific
issues. Scientists are represented in the Management C ommittee by the
program and topic speakers. The Scientific Review Committee as expert body
also advises the Board of Directors on important scientific matters.
Members of the Board of Directors
Prof. Dr. Günther Wess
CEO
Dr. Nikolaus Blum
CFO
Dr. Alfons Enhsen
CTO
Members of the Supervisory Board
Chair
MinDir’in Bärbel Brumme-Bothe
Federal Ministry of Education and Research
MinR Dr. Christian Greipl
Federal Ministry for the Environment, Nature
Conservation and Nuclear Safety
Vice Chair
MDirig. Dr. Ronald Mertz
Bavarian State Ministry of Economic Affairs and
Media, Energy and Technology
MinR Ulrich Reithmann
Bavarian State Ministry of Finance, Regional
Development and Regional Identity
MinR’in Maria Becker
Federal Ministry of Health
As of June 2014/ Within the framework of the new Partnership Agreement, changes in the composition of the Supervisory Board are
being made.
Members of the Scientific Advisory Board
Chair
Professor Hillel Koren
Environmental Health, LLC Durham,
North Carolina, USA
Professor Stephanie J. London
National Institute of Environmental
Health Sciences, Research Triangle Park, North
Carolina, USA
Vice Chair
Professor Steve Brown
MRC Harwell, Harwell Science and Innovation
Campus, Oxfordshire, UK
Dr. Manfred Rösner
mroe-consulting, Eppstein, Germany
Professor Amnon Altman
Head, Division of Cell Biology, La Jolla Institute
for Allergy & Immunology, California, USA
Professor Elizabeth Fisher
UCL Institute of Neurology, London, UK
Professor Edda Klipp
Humboldt-Universität zu Berlin, Department of
Biology, Germany
Professor Geoff J. Laurent
Centre for Cell Therapy and Regenerative Medicine, University of Western Australia, Nedlands,
Australia
Professor Edward H. Leiter
The Jackson Laboratory, Bar Harbor, Maine, USA
Professor Urban Lendahl
Department of Cell and Molecular Biology (CMB),
Karolinska Institutet, Stockholm, Sweden
Professor Sisko Salomaa
STUK, Radiation and Nuclear Safety Authority,
Research and Environmental Surveillance,
Helsinki, Finland
Professor Christine Foyer
Centre for Plant Sciences, University of Leeds, UK
Professor Bernhard Wehrli
ETH Zurich, Institute of Biogeochemistry and
Pollutant Dynamics, Switzerland
Professor Stephen C. Woods
Department of Psychiatry, University of
Cincinnati, Ohio, USA
IMPRINT
Published by:
Helmholtz Zentrum München –
German Research Center for
Environmental Health (GmbH)
Ingolstädter Landstrasse 1
D-85764 Neuherberg
Germany
T +49 (0) 89 3187–0
F +49 (0) 89 3187–3324
www.helmholtz-muenchen.de
Editors and Authors:
Sonja Opitz, Cordula Klemm,
Sonja Duggen, Dr. Nadja Becker,
Corporate Communications
Dr. Hans Guldner, Dr. Brigitte Röthlein
[email protected]
Translated by:
Carol Oberschmidt, Berlin
Online Realization:
Marion Kuchler, Susanne Eichacker
Graphic Design:
heller & partner communication GmbH
Munich
Photographs:
Jan Roeder, Munich
Michael Haggenmüller; Ingo Kniest;
NASA; DFG/Humboldt Foundation David
Ausserhofer; Hans Steininger,
Helmholtz Association of German
Research Centres H. Scherm; Vincent
Breysacher
Printed by:
Gotteswinter und Aumaier GmbH
Munich
ISSN: 0941-3847
Excerpts from the articles in this publication may be reproduced without further
permission, provided that Helmholtz
Zentrum München – German Research
Center for Environmental Health is
mentioned. All other rights are reserved.
© Helmholtz Zentrum München 2014
The Helmholtz
Association
The Helmholtz Association of German Research Centres is Germany’s largest
scientific research organization. Altogether, 36 000 people currently work
in its 18 scientific-technical and biological-medical research centers. The
Association’s annual budget amounts to more than 3.8 billion euros.
The mission of the Helmholtz Association is research to make a major
contribution to solving grand challenges which face society, science and
industry. To succeed in meeting these responsibilities, the Association
concentrates its work in six research fields: Energy, Earth and Environment,
Health, Aeronautics, Space and Transport, Key Technologies and Structure
of Matter.
For each of these fields, scientists develop research programs which
are evaluated by international experts. Their evaluation forms the basis
for the program-oriented funding given to Helmholtz research. Within
the six research fields, Helmholtz scientists cooperate with each other and
with external partners – working across disciplinary, organizational
and national borders.
German Research Center for
Environmental Health (GmbH)
Ingolstädter Landstrasse 1
D-85764 Neuherberg
Germany
T +49 (0) 89 3187–0
F +49 (0) 89 3187–3324
www.helmholtz-muenchen.de

pdf version - Helmholtz Zentrum München

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