IMT Annual Report 2010

Transcription

Annual Report 2010
Institute of Medical Technology
University of Tampere
1
INDEX
Foreword...........................................................................
4
About IMT
IMT Personnel..................................................................
IMT Board and Scientific Advisory Board......................
IMT Administration.........................................................
6
7
8
Strategy, Mission, Vision.................................................
Research programs..........................................................
10
11
Research groups
Bioinformatics.................................................................
Protein Dynamics Group................................................
Molecular Biotechnology................................................
Cancer Biology................................................................
Cancer Genomics............................................................
Genetic Cancer Predisposition........................................
Molecular Biology of Prostate Cancer.............................
Biochemistry of Cell Signaling........................................
Cell Interactions...............................................................
Mitochondrial Gene Expression and Disease..................
Mitochondrial Biogenesis in Health and Disease............
Mitochondrial Gerontology and Age-related Diseases....
Mitochondrial DNA Maintenance.................................
Genetic Immunology.......................................................
Immunoregulation...........................................................
Experimental Immunology..............................................
Molecular Immunology...................................................
Coeliac Disease...............................................................
Tissue Biology.................................................................
12
14
16
17
19
20
21
22
24
25
27
28
29
30
32
33
34
35
37
Education
Biotechnology program...................................................
Master’s Degree Program in Bioinformatics...................
Tampere Graduate Program in Biomedicine and
Biotechnology.................................................................
IMT Annual Report 2010
Publisher
Institute of Medical Technology 2011
Editor
Tapio Visakorpi, Professor
Sub-editor
Jaana Salmensivu-Anttila, Administrator
Photographs
All IMT Research Groups
Jukka Lehtiniemi
Front-page image
“1DDZ” by Martti Tolvanen
Page layout
Jukka Lehtiniemi, ADP
38
39
40
All publications 2010........................................................ 42
2
Annual Report 2010
3
Foreword, IMT 1995-2010
As from the beginning of 2011 IMT will be the central part of the Institute of
Biomedical Technology, so this will be the last Annual Report from IMT. The new
institute will consist of units operating in biomedical and translational research and its
exploitation, and will offer universities in Tampere Region an excellent opportunity
to develop a high quality interdisciplinary center ready to meet present and future
challenges.
IMT was a success story. Fifteen years ago a few scientists were brought into an
empty building in the middle of Kauppi forest, and that initiative developed into
an international high quality research and education center. I want to thank all our
personnel over the years; you made this happen. The founder Prof. Kai Krohn, our
collaborators and supporters are all warmly thanked.
From IMT photograph arc
hives
It is our duty to ensure that the legacy of IMT in high quality research and education
will flourishes and develops further in the new institute.
Olli Silvennoinen
4
Annual Report 2010
5
IMT Personnel
IMT consists of fifteen research groups and two affiliated groups with a total staff
of some 180. This includes project leaders, senior and post-doctoral researchers,
PhD students, laboratory technicians and other personnel. About 67% of the staff
iareacademic scientists, 26% research support staff while 7% work in administration.
About 20% of the personnel are foreigners.
The major resource of IMT is professionally skilled, highly educated and motivated
personnel. The Institute is committed to developing the working environment
for all its employees. Integral parts of the personnel policy are providing a good
working environment, career development opportunities a rewarding system of
remuneration and addressing equal opportunity issues. Continuing education is
provided for the entire personnel. The IMT personnel can participate in activities
intended to maintain working ability including support for sporting activities. In
addition the Institute has its own bi-annual event to promote well-being at work
and foster team spirit.
The research strategies and institutional policies are openly discussed at monthly
group leader meetings, thereby providing an opportunity for all scientists to
influence the decisions and strategies. Institutional policies and recruitment
strategies are also discussed at IMT staff meetings providing an opportunity for all
personnel to participate in the decision-making.
Members of the Board 1.1.2010-31.12.2010
(Primary member, position and personal deputy member)
Nordback Isto, Chairman, Director, Division of surgery, gastroenterology and oncology, TAUH
Turjanmaa Väinö, MD, Tauh
Prof. Kallioniemi Anne, IMT
Prof. Visakorpi Tapio, IMT
Prof. Kulomaa Markku, IMT
Prof. Parkkila Seppo, IMT
Prof. Isola Jorma, IMT
Prof. Vihinen Mauno, IMT
Prof. Hurme Mikko, Faculty of Medicine
Skottman Heli, Senior Researcher, Regea
Rovio Anja, Project Manager, IMT
Schleutker Johanna, Principal Investigator, IMT
Hinkka Janette, Laboratory technician, IMT
Valanne Susanna, Research Fellow, IMT
Wahlfors Jarmo, Research Development Director, University of Tampere
Salminen Tiina, Project manager, University of Tampere
Uusi-Rajasalo Harri, City of Tampere
Tainio Hanna, Medical Advisor, MD, PhD, City of Tampere
Eskola Matti, Managing director, Finn-Medi Research
Valimaa Tero, Director, Finn-Medi Research
Ojala Elina, Student
Siivonen Joonas, Student
Prof. Silvennoinen Olli, Presenting official
Salmensivu-Anttila Jaana, Administrator, Secretary
6
IMT Administration
SAB Scientific Advisory Board
IMT is led by a ten-member Board representing the University of Tampere and
surrounding institutions, such as the City of Tampere, Tampere University Hospital
(TAUH) and biotechnology companies. The Board also includes representation
of professors, other personnel and the students of IMT. The Director serves the
presenting official for the Board and is responsible for most of the research-related
and administrative decisions. IMT’s administration consists of a laboratory chief,
a coordinator and an amanuensis (MSc program), an administrator, a financial
assistant and clerical staff.
The Scientific Advisory Board consists of four distinguished scientists. The duties of the SAB are to issue statements on the
competence of applicants for the post of director, to evaluate the scientific programs of the Institute and rolling tenure track
professors, and to formulate initiatives and provide statements on new research programs.
Annual Report 2010
Prof. Carl-Henrik Heldin, Ludwig Institute for Cancer Research, Uppsala, Sweden
Prof. Marja Jäättelä, Danish Cancer Society, Copenhagen, Denmark
Prof. Juha Kere, Department of Biosciences and Nutrition, Novum, Huddinge, Sweden
Prof. Kjetil Taskén, The Biotechnology Centre of Oslo, Oslo, Norway
7
Funding 2010
External funding
Ministry of education and Univ.of Tampere
10
Administrative personnel 2010
8
Administrator
Jaana Salmensivu-Anttila
Coordinator
Marjatta Viilo
Amanuensis
Riitta Aallos
4
2
53%
21% 7%
6% 6% 4% 3% 2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
0
1996
Total
11,5 m€
6
1995
Laboratory chief
Anja Rovio
Million euros
Director
Olli Silvennoinen, Director
Tapio Visakorpi, Vice Director
Budget
Academy of Finland
Biocenter Finland
European Union
Foundations
EVO
Own Income Financing, University Alliance, etc.
Financial Affairs
Kaarin Forsman
Departmental Secretary
Suvi-Elina Kalliola
Erika Säynässalo (16.8.2010 -)
Personnel 2010
Office Secretary
Maria Bergman, Office Secretary -28.2.2010
180
Study Secretary
Mira Pihlström
120
Academic researchers
Research support staff
Administration
160
140
100
80
60
20
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
0
1995
Staff altogether
171 persons
40
73% Researchers
21% Support staff
6% Administration
8
Annual Report 2010
9
Research Programs
Strategy, Mission, and Vision
The IMT strategy for the years 2006 – 2010 sees the Institute
as a modern, internationally competitive research and teaching
institute of the University of Tampere. The main focuses are
medical technology and biotechnology. The Institute’s role as a
developer of the above- mentioned focus areas is the principaltheme
of our strategy.
Developing of high quality biomedical and biotechnology research
and teaching is our mission. Our Institute is a dynamic research
and education institution, where synergistic research and
teaching areas lay the foundations for modern multidisciplinary
research projects and commercial applications. The main aim is to
integrate education, research and development into a tight unity
where the three different aspects support each other.
The FinMIT Centre of Excellence, based in IMT and in Biomedicum Helsinki, was recently
granted on extension for a further six years, from 2008 to 2013, under the title ‘Centre of
Excellence in Research on Mitochondrial Disease and Ageing’. FinMIT combines the efforts
of four research groups, those of Hans Spelbrink and Howy Jacobs in IMT Tampere, and of
Brendan Battersby and Anu Suomalainen in Biomedicum Helsinki, to develop new knowledge
about the role of mitochondria in human disease, including the degenerative diseases of old age,
and to use this knowledge to develop novel diagnostic and therapeutic tools for the benefit of
patients and their families. The work is undertaken primarily using model organisms such as
Drosophila and the zebrafish, but also involves the analysis of clinically derived cell-lines and
DNAs, and the use of in vitro systems to better understand the biochemistry of mitochondrial
function. The Translational Prostate Cancer Research Program (TPCRP) was established on the
campus of the University of Tampere and Tampere University Hospital (TAUH) in the early
1990’s. Today, the core of TPCRP consists of three research groups: Genetic Predisposition
to Prostate Cancer (GPPC), led by Professor Johanna Schleutker; the Molecular Biology
of Prostate Cancer group (MBPCG), led by Prof. Tapio Visakorpi; and the Department of
Urology (DoU), led by Prof. Teuvo Tammela.
The overall aim of the TPCRP is to form close interactions between basic scientists and
clinicians to provide an excellent basis for translational research and education. The unique
collection of population-based clinical materials and models with complementary expertise
provides exceptionally good preconditions to study prostate cancer. Special emphasis is placed
on the training of basic scientists and clinicians so that they understand each other and to foster
their clinical researcher careers.
Vactia - The Center for Vaccine Research and Immunology.
Vaccine development and immunology have been recognized as strategic competence areas of
the University of Tampere. Tampere is the leader in vaccine research in Finland. For example,
the largest trials in Finland studying the efficacy of vaccines are conducted by the Vaccine
Research Center. In order to develop vaccine research further in Tampere, key operators in the
field have joined forces to create Vactia – The Center for Vaccine Research and Immunology.
The founding members of Vactia include the Vaccine Research Center, the Department of
Virology, Finn-Medi Research, the Institute of Medical Technology, STD-Vaccine Research,
Fit Biotech and Vactech. In total, Vactia includes of nearly 200 researchers and aims to promote
vaccine development – from basic research to clinical trials – and to facilitate the establishment
of new spin-off companies.
Biocenter Finland Funded Core Facilities
The University of Tampere Drosophila Core facility, funded by Biocenter Finland, is a facility
promoting the use of the model organism Drosophila melanogaster in life sciences. The services
offered by the Drosophila core facility include obtaining transgenic flies of interest, consultation
and guidance on the experimental setting, and ordering and maintenance of fly lines. More
information can be found at: http://cofa.uta.fi/drosophila_index.php
University of Tampere Zebrafish Core facility, funded by Biocenter Finland, serves all
scientists using zebrafish as a research model system. The new facility is capable of housing
up to 50,000 adult zebrafish. Zebrafish provide a vertebrate model where many advantages of
lower invertebrate model organisms are combined with the benefits of mammalian research
models. Such advantages include embryonic development ex utero, transparency of embryos and
rapid embryonic development. Zebrafish core facility services include e.g. housing of zebrafish,
morpholino injections and F3 homozygous mutant carrier families for genetic screening. More
info at: http://cofa.uta.fi/zebra_index.php
10
Annual Report 2010
11
Bioinformatics
The goal of the Bioinformatics Group is to understand biological and medical phenomena at the structural, mechanical
and systems level by applying and developing bioinformatics tools and applications. The Group has two major research
lines.
Analysis and prediction of the effects of variations ranges from collecting information into publicly accessible databases
to detailed structural and functional studies of the effects and consequences of the variations. Currently we maintain
about 140 variation databases (http://bioinf.uta.fi/). These databases mainly contain information on immunodeficiencies
and cancers. The effects and consequences of the variations are investigated at RNA, DNA and protein level. The ultimate
goal is to help in developing new therapies to treat patients. We are developing tools for the prediction of numerous
effects on protein structure, function, interactions, stability, aggregation and disorder propensity etc. For this purpose
we provide the Pathogenic-Or-Not-Pipeline (PON-P), that allows easy and fast access to a large number of predictors
and interpretation of the predictions. We have successfully predicted the effects of thousands of variations. We have also
investigated the performance of numerous prediction methods with large test sets. For these studies we have collected
benchmark datasets in VariBench, a suite for high-quality experimentally verified variation information.
Bioinformatics
The aim of the Bioinformatics Group is to understand biological and medical phenomena in structural, mechanical and systems level by applying
bioinformatics tools and applications.
The other research line is systems biology of the immune system. We have identified genes and proteins essential
to human immunity. The evolution of these genes and proteins has been investigated and a database generated for
about 1,500 proteins. These datasets allow system wide analysis of immunity. We have investigated and simulated
certain immunological processes based on immunome interactome (protein-protein-interactions) and gene expression
information. These studies have revealed new features of biological networks and allowed e.g. successful prediction of
novel primary immunodeficiency (PID) candidate genes. Another approach to investigating the immune system at
system level is to follow gene and protein expression during B-cell development by applying microarray and proteomics
methods. We are now applying systems immunological approaches to study the mechanisms of PIDs to learn how these
diseases could be efficiently treated on system level.
Main collaboration
Professor Tapio Salakoski, Deparment of Information Technology, University of Turku, Finland; Professor Harri
Savilahti, Department of Biology, University of Turku, Finland; Professor C. I. Edvard Smith, Karolinska Institutet,
Stockholm, Sweden; Human Genome Variation Society board members; Immunodeficiency diagnostic and research
laboratories; European Bioinformatics Institute.
Funding
Academy of Finland, Medical Research Fund of Tampere University Hospital, Sigrid Juselius Foundation, Biocenter
Finland.
Personnel
Group Leader:
Post-doctoral Fellow:
PhD Students:
Undergraduate Students:
Other staff:
12
Annual Report 2010
Professor Mauno Vihinen, PhD
Csaba Ortutay, PhD
Sofia Khan, MSc
Johanna Salonen, MSc
Crina Samarghitean, MD, MSc
Janita Thusberg, MSc
Jouni Väliaho, MSc
Heidi Ali
Ayodeji Olatubosun
Preethy Nair
Jani Härkönen
Sreevani Kotha
Percy Nutifafa Hevor
Abhishek Niroula
Saija Sorsa
Martti Tolvanen, PhLic
Hannu Korhonen, system manager
13
Protein Dynamics Group
Conformational changes in proteins are important for protein function, including ligand recognition, protein-protein
interactions and chemical modifications of proteins. The Protein Dynamics Group uses experimental and computational
methods to elucidate the importance of changes in protein conformation and protein interactions caused by mechanical
stress.
Our major focus is to on exploring the structural dynamics of the proteins in cellular adhesion sites called focal adhesions.
We are focus particularly on talin and vinculin, two proteins in the complex that connects the actin cytoskeleton to the
integrin receptors on the cell surface. We also engage in material research to develop novel biosensors and better tools for
gene transfer. In addition, we participate in research focusing on avidin-biotin technology in collaboration with Professor
Kulomaa.
The experimental tools include recombinant proteins and mutagenesis, interaction analysis methods, fluorescence
spectroscopy and optical microscopy. Computational biology makes it possible to understand the protein behavior at
atomic resolution, and we use molecular dynamics simulations as a main tool.
Biocenter Finland plays an important role in our operation and we provide services in protein production and protein
analysis.
Biotechnology
Main collaborators
The biotechnology groups study and engineer proteins to understand
their structure-function relationships and to apply them in diagnostics,
vaccination and materials science
Professors Mark S. Johnson and J. Peter Slotte, and Docent Tomi Airenne, Åbo Akademi University; Professor Janne
Jänis, Dr. Maija Lahtela-Kakkonen and Dr. Mikael Peräkylä, University of Eastern Finland; Professor Janne Ihalainen,
Docents Maija Vihinen-Ranta and Jussi Toppari, University of Jyväskylä; Professor Kristiina Takkinen, VTT Technical
Research Center of Finland, Espoo; Docent Perttu Permi, University of Helsinki; Professors Seppo Parkkila, Timo
Vesikari and Heikki Hyöty, University of Tampere.
Professor Oded Livnah, Hebrew University of Jerusalem, Israel; Professor Viola Vogel, ETH Zürich, Switzerland; Dr.
Bernhard Wehrle-Haller, University of Geneva, Switzerland, Professor Peter Hinterdorfer, Dr. Andreas Ebner and Dr.
Hermann Gruber, Johannes Kepler Universität Linz, Austria Funding
Academy of Finland, Biocenter Finland, Sigrid Jusélius Foundation, Health District of Pirkanmaa, The National
Graduate School in Informational and Structural Biology (ISB)
Personnel
Group Leader:
Post-doctoral Fellows:
PhD Students:
Laboratory staff:
14
Annual Report 2010
Docent Vesa Hytönen, PhD
Juha Määttä, PhD
Jenita Pärssinen, PhD
Sampo Kukkurainen, MSc
Barbara Niederhauser, MSc
Henrik Hammarén
Joonas Siivonen
Outi Väätäinen
15
Molecular Biotechnology Group
Protein engineering and protein design followed by the many sided analyses of the functional and structural properties of the products
are the major experimental approaches in the Molecular Biotechnology (MBT) Group in IMT. Bacterial and eukaryotic expression
systems are used to produce the recombinant proteins, and site-directed and random mutagenesis (phage display, DNA-shuffling) for
genetic modification of the proteins. Functional characterization of the proteins engineered and their interactions, particularly with
small ligands, are performed using a wide variety of biochemical and biophysical methods. They include, for instance, surface plasmon
resonance (SPR), optical biosensors (Biacore), fluorescence spectroscopy, isothermal titration (ITC) and differential scanning (DSC)
calorimetry, atomic force microscopy (AFM), and light scattering analyses. Computational methods, for example molecular modeling
and molecular dynamics simulations, are also used in protein design and analysis. Structural analysis of the engineered proteins by
X-ray crystallography, NMR, and cryo-EM is performed by our national and international collaborators.
The research in the MBT group focuses on four topics: 1. Engineering of biotin-binding proteins, aiming at the development of novel
protein tools for bio- and nanotechnology. This includes the development of avidins carrying heterogenous binding sites in a single
molecule, the development of novel ligands for avidins, and the engineering of avidins with efficient immobilization capabilities. 2.
Production and characterization of virus proteins and virus-like particles for the development of diagnostics and vaccines. 3. Use of
biological macromolecular building blocks for the development of improved and new biofunctional nanostructures. 4. Design and
production of ultra sensitive, stable and easy to use atomic force spectroscopy (AFM) biosensor tips (Intellitip).
Docent Vesa Hytönen was appointed Group Leader position in IMT, and therefore, started his own Protein Dynamics (PD) Group
at beginning of August, 2010. Three other scientists and a technician moved with him from the MBT group to the PD group.
However, active collaboration between our groups continues. We use the same laboratory facilities and technical approaches and
hold group meetings together.
Main collaborators
Cancer Research
The cancer research groups aim to identify the molecular mechanisms
of cancer and translate the information into new clinical tools.
Professors Mark S. Johnson and J. Peter Slotte, and Docent Tomi Airenne, Åbo Akademi University; Professors Janne Jänis,
Seppo Ylä-Herttuala and Kari Airenne, Dr. Maija Lahtela-Kakkonen and Dr. Mikael Peräkylä, University of Eastern Finland;
Professors Kari Rissanen, Docents Maija Vihinen-Ranta, Varpu Marjomäki, University of Jyväskylä; Professor Kristiina Takkinen,
VTT Technical Research Center of Finland, Espoo; Docent Perttu Permi, University of Helsinki; Professors Seppo Parkkila, Timo
Vesikari and Heikki Hyöty, University of Tampere. Professor Oded Livnah, Hebrew University of Jerusalem, Israel; Professors Meir
Wilchek and Edward Bayer, Weizmann Institute of Sciences, Rehovot, Israel; Professor Viola Vogel, ETH Zürich, Switzerland;
Professor Peter Hinterdorfer and Dr. Andreas Ebner, Johannes Kepler Universität Linz, Austria; Professor Peter Schurtenberger,
Drs. Herve Dietsch and Christian Moitzi, University of Fribourg, Switzerland. Funding
Academy of Finland, The Finnish Funding Agency for Technology and Innovation (TEKES), MNT-ERA.net, Health District
of Pirkanmaa, The National Graduate School in Informational and Structural Biology (ISB), and Tampere Graduate School in
Biomedicine and Biotechnology (TGSBB).
Personnel
Group Leader:
PhD Students:
16
Professor Markku Kulomaa, PhD
Docent Vesa Hytönen, PhD (until 31.7.2010)
Satu Helppolainen, PhD (until 28.2.2010)
Anssi Mähönen, PhD
Juha Määttä, MSc, PhD 18.6.2010 (until 31.7.2010)
Tiina Riihimäki, MSc
Tiia Koho, MSc
Jenni Leppiniemi, MScEng
Barbara Niederhauser, MSc (until 31.7.2010)
Sampo Kukkurainen, MSc (until 31.7.2010)
Soili Hiltunen, MSc
Laboratory staff:
Annual Report 2010
Other staff:
Suvi Varjonen
Selina Mäkinen
Toni Grönroos
Elina Ojala
Ulla Kiiskinen, technician
Tanja Heinonen (Vactech Oy)
Joanna Zmurko, work
placement student
(Univ. Glasgow)
Tuomas Mäntylä, MSc
17
Cancer Biology
Cancer Genomics
Trastuzumab is a recombinant monoclonal antibody drug that is widely used in the treatment of breast cancer. Despite encouraging
clinical results, some cancers are primarily resistant to trastuzumab, and a majority of these initially responding become resistant
during prolonged treatment. We have previously established an experimental research model for trastuzumab resistance (cell line
JIMT-1) by using cells from a drug-resistant patient. JIMT-1 cells are intrinsically resistant to trastuzumab in vitro, but the direct
mechanism(s) for drug resistance remains uncertain, despite numerous published reports by us and other groups.
Breast and pancreatic cancers are among the most common causes of cancer deaths in industrialized countries and thus constitute an
important cause of morbidity and mortality. The main focus of the Cancer Genomics Research Group is the identification of genes
and molecular pathways that are critical for the development and progression of these tumor types, as they are likely to provide new
diagnostic tools or therapeutic targets for the clinical management of breast and pancreatic cancer.
Although it has been reability documented that trastuzumab inhibits mitotic and apoptotic signaling via cell surface receptor tyrosine
kinases, an increasing number of studies suggest that the main mechanism of action is mediated by the lymphocytic immune
reaction evoked by trastuzumab bound to the cancer cells. We have recently shown that immune effector cells (mainly natural killer
T lymphocytes) react equally well in breast cancer cell lines irrespective of the direct resistance in mitotic cell signaling (Barok et al.).
The immune mechanisms are likely to be more important in the treatment of early (submacroscopic but disseminated) cancer, which
is the best target for anti-HER2 therapy. We aim to monitor CTCs and DTCs in our xenograft mouse tumor models, and study
whether trastuzumab has an inhibitory effect on CTCs and DTCs at the time when the primary tumor has already grown too large
to be growth-inhibited by trastuzumab and the immune system. According to our hypothesis, single tumor cells shed into the blood
stream may differ in their trastuzumab sensitivity, since there are no surrounding connective tissue glycosaminoglycans and/or other
cell surface molecules responsible for epitope masking. These studies are intended to form an experimental basis for the molecular
diagnostics of circulating HER-2 positive tumors cells.
Our research also includes medical imaging and virtual microscopy (i.e., viewing and handling digitized microscope specimens
with computers). We have developed free image software tools for automated scanning, analysis, viewing, network transmission,
and clinical DICOM linkage (Tuominen et al.). Please see our website for more details: http://jvsmicroscope.uta.fi/.
Main collaborators
University of Helsinki, Department of Oncology & Biomedical Informatics Group; University of Lund, Department of Oncology,
Sweden; University of Debrecen, Hungary.
Funding
The Finnish Cancer Foundation, Sigrid Juselius Foundation and Medical Research Fund of Tampere University Hospital (EVO).
Personnel
Group Leader:
PhD Students:
Undergraduate Student:
Laboratory staff:
Other staff:
18
In pancreatic cancer, we are focusing our efforts on the study of genes that are activated through DNA amplification during cancer
pathogenesis. To this end, we have applied a combination of high-throughput microarray based screening techniques and traditional
positional cloning methods to identify regions of the genome that are commonly amplified in pancreatic cancer cell lines and to
pinpoint actual putative amplification target genes. The functional role of these genes in cancer development is then studied in cell
line model systems. The possible clinical significance of these newly identified molecular targets is being evaluated in a large series of
pancreatic cancer patients using tissue microarray technology. Together these studies aim at elucidating the possible contribution of
the putative amplification target genes to pancreatic cancer pathogenesis.
Main collaborators
Professor Daniel von Hoff, University of Arizona, USA; Drs. Spyro Mousses and David Azorsa, Translational Genomics Research
Institute, AZ, USA; Professor Guido Sauter, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Dr. Sampsa
Hautaniemi, Computational Systems Biology Laboratory, Institute of Biomedicine, University of Helsinki, Finland; Dr. Reija Autio,
Signal Processing Unit, Tampere Technical University, Finland; Professor Kaija Holli, Medical School, University of Tampere,
Finland; Dr. Heini Huhtala, School of Public Health, University of Tampere, Finland.
Funding
The Academy of Finland, the Sigrid Juselius Foundation, the Finnish Cancer Organizations, the Medical Research Fund of Tampere
University Hospital, the National Institutes of Health (USA).
Personnel
Professor Jorma Isola, MD, PhD
Minna Tanner, MD, PhD, Docent
Mark Barok, MD, PhD
Synnöve Staff, MD, PhD
Jukka Pitkänen, MD, PhD
Group Leader:
Katri Köninki, MSc
Vilppu Tuominen, MSc
Teemu Tolonen
PhD Students:
Laura Partanen
Kristiina Ryömä, Bioanalyst
Sari Toivola, Laboratory technician
Eeva Pesonen, Bioanalyst
Laboratory staff:
Ulla Saarela, Coordinator
In breast cancer, we are exploring the role of bone morphogenetic proteins, especially BMP4 and BMP7, in cancer development.
BMPs are extracellular signaling molecules that control various cellular processes, such as proliferation, differentiation, apoptosis and
migration by regulating target gene transcription. They have essential roles during embryogenesis and organogenesis but are also
implicated in cancer pathogenesis. We are studying the functional relevance of BMP4 and BMP7 signaling in breast cancer by using
well-established breast cancer cell line model systems. Using large tumor materials we are also evaluating the clinical significance of
various BMP signaling pathway components and thereby the possible clinical utility of these molecules in breast cancer.
Annual Report 2010
Professor Anne Kallioniemi, MD, PhD
Kimmo Savinainen, PhD
Emma-Leena Alarmo, PhD
Alejandra Rodriguez Martinez, PhD
Johanna Ketolainen, MSc
Riina Kuuselo, MSc
Eeva Laurila, MSc
Laura Rantanen
Minna Ampuja
Riikka Laurila
Kati Rouhento, Technician
19
Genetic Cancer Predisposition
Molecular Biology of Prostate Cancer Group (MBPCG)
Genetics seem to have a major role in susceptibility to cancer. Although the actual inherited cancer syndromes cause only about
1% of all cancers, a much greater proportion of the overall cancer risk may be explained by heritable factors. For prostate and breast
cancer – the most common cancers in males and females – the repective estimates are 42% and 27%. Genes found to be affected
in hereditary cancers can lead to the discovery of new pathways and processes relevant to carcinogenesis. These genes can also be
inactivated by somatic mutation or epigenetic modification in sporadic cancers.
The Molecular Biology of Prostate Cancer Group (MBPCG) studies somatic genetic alterations in prostate cancer with emphasis
on alterations associated with disease progression. Finding the common genetic alterations is an important step in the development
of better diagnostics and therapeutics.
Two major research lines are pursued by the MBPCG:
1. The search for prostate cancer oncogenes and tumor suppressor genes. Microarray and next generation sequencing technologies
are used to analyze differential expression, epigenetic changes as well as gene copy number alterations. Special emphasis is placed
on non-coding RNAs (ncRNA), especially on microRNAs (miRNA). The clinical significance of these genes is evaluated with
the aid of population based tissue microarrays and their function is analyzed in cellular models – the ultimate goal being the
development of novel diagnostic and therapeutic tools.
2. Characterization of the AR signaling pathway in the tumorigenesis of prostate cancer. Over 60 years after the discovery of the
importance of androgens in prostate cancer, there is still no curative treatment for castration-resistant prostate cancer. MBPCG
is exploring strategies to therapeutically interfere with androgen signaling. The androgen receptor (AR) itself is a potent therapy
target, but downstream target genes or AR co-factors might also provide means for therapeutic intervention. A new ARoverexpression model for prostate cancer has been developed by the group to identify these genes and co-factors, and to study
their functional significance. Several such protein-coding genes and miRNAs have already been identified with the help of the
model. Currently their significance is under investigation. One known downstream target gene of AR signaling is the oncogenic
transcription factor ERG (and some of its family members) which is recurrently fused with TMPRSS2 (or other androgenregulated genes) in prostate cancer. The significance of the fusion driven overexpression is also under investigation.
Our main focus is on prostate cancer (PrCa) genetics and we are also working on the genetic bases of hereditary breast cancer. There
is genetic predisposition to aggressive cancer and cancer specific deaths. Therefore genetic markers should be found that could be
used as to identify individuals at elevated risk. Currently in PrCa, however there are no reliable means to accurately distinguish
risk for life-threatening, aggressive PrCa from the overwhelming majority of indolent cases. Therefore we aim to 1) identify new
risk factors and explain their functionality in prostate carcinogenesis. This would have diagnostic applicability, especially for more
aggressive disease, at an early, curable stage, and 2) develop tools for prognostic purposes, i.e. prognostic biomarkers, which are
urgently needed in clinical practice. We combine traditional genetic analyses with functional genomics and array-based applications.
Multiple methods are used in order to identify genes that are mutated, differentially expressed or copy-number altered.
Main collaborators
CPCG (International Consortium for Prostate Cancer Genetics); PRACTICAL (Prostate Cancer Association Group to Investigate
Cancer Associated Alterations in the Genome); ProspeR (Prostate cancer: profiling and evaluation of ncRNA); TPCRP (Translational
Prostate Cancer Research Program); Professor Anssi Auvinen and Professor Hannu Oja, Departments of Epidemiology and
Biostatistics at the Tampere School of Public Health and Dr. Joan Bailey-Wilson, National Institutes of Health (USA).
Funding
The Academy of Finland, Finnish Cancer Organizations, the Sigrid Juselius Foundation, the Reino Lahtikari Foundation, the
National Institutes of Health (USA), Medical Research Fund of Tampere University Hospital (EVO).
Personnel
Group Leader:
PhD Students:
Laboratory staff:
Other staff:
20
Main collaborators
EU-FP7-ProspeR consortium; EU-FP7-PRO-NEST; Professor Robert Vessella (University of Washington, USA); Dr. Steven
Bova ( Johns Hopkins University, USA); Professor Jorma Palvimo (University of Kuopio, Finland); Professor Olli Jänne (University
of Helsinki, Finland); Dr. Matti Nykter and Dr. Harri Lähdesmäki (Tampere University of Technology, Finland); TPCRP
(Translational Prostate Cancer Research Program)
Funding
Professor Johanna Schleutker, PhD
The Academy of Finland, the European Commission, the Medical Research Fund of Tampere University Hospital, the Sigrid
Jusélius Foundation, the Cancer Society of Finland, the Reino Lahtikari Foundation, OrionPharma Ltd
Tiina Wahlfors, PhD
Personnel
Sanna Pakkanen, MD
Sanna Siltanen, MSc
Kirsi Kuusiato, MSc
Riikka Nurminen, MSc
Daniel Fischer, MSc
Virpi Laitinen, MSc
Group Leader:
Aleksandra Bebel
Ekaterina Slitikova
PhD Students:
Linda Enroth, Technician
Riitta Vaalavuo, Research Nurse
Riina Liikala, Technician
Clinical contributors:
Professor Teuvo Tammela, MD, PhD
Mika Matikainen, MD, PhD
Annual Report 2010
Professor Tapio Visakorpi, MD, PhD
Merja Helenius, PhD
Kati Porkka, PhD
Outi Saramäki, PhD
Leena Latonen, PhD
Kati Waltering, PhD
Hanna Rauhala, PhD
Laboratory staff:
Visa Manni
Erinn-Lee Ogg, placement student
Simone McSeveney, placement student
Mariitta Vakkuri, technician
Päivi Martikainen, technician
Sanni Jalava, MSc
Anchit Khanna, MSc
Saara Lehmusvaara, MSc
Katri Leinonen, MSc
Mauro Scaravilli, MSc
Hanna Suikki, MSc
Kirsi Tuppurainen, MSc
Alfonso Urbanucci, MSc
Erik Veskimäe, MD
Teemu Tolonen, MD
Rasa Sabaliauskaite, ERASMUS student
21
Cell Interactions
Our main interest is in the role of ADAM metalloproteinase-disintegrins in intercellular communication. ADAMs are the principal
ectodomain sheddases which can activate growth factors, cytokines, and other mediators from their membrane-bound precursors as
well as down-regulate receptors and adhesion proteins. ADAMs can also mediate cell adhesion. We address the molecular mechanism
of physiological ADAM regulation and the altered ADAM regulation in pathological conditions, particularly in vascular disease
and cancer.
We have identified the Src-homology-3 (SH3) proteins interacting with human ADAMs as candidate regulators of their activity
and targeting. ADAMs appear to have characteristic SH3-binding profiles with some specific and some common interactions. These
studies have been carried out in collaboration with Prof. Saksela’s laboratory (University of Helsinki). Further characterization of
select ADAM-SH3 interactions in cells is ongoing.
Cellular Biology
We are particularly interested in human ADAM15, implicated both in physiological and pathological processes through ectodomain
shedding and cell-cell interactions. We have shown that the alternative ADAM15 exons are differentially used in human tissues,
giving rise to mRNA variants encoding ADAM15 isoforms with cytosolic tails carrying different complements of SH3-interaction
motifs. The alternative ADAM15 tails show differential SH3-binding, suggesting that ADAM15 function is regulated at the level
of differential alternative exon use.
The alternative ADAM15 exon use is misregulated in human cancers. The tumors are distributed into a few different clusters
according to their ADAM15 mRNA variant profiles, suggesting that different variant patterns reflect specific defects in the splice
control mechanism. Misregulated ADAM15 splicing appears to be associated with clinical traits such as EGFR status and tumor
angiogenesis.
We investigated the misregulation of ADAMs in the vascular diseases in collaboration with the Tampere University Hospital and the
AtheroRemo Consortium. Several ADAMs have been implicated in atherosclerosis and sudden cardiac death.
Altogether, our recent results provide novel insights into ADAM regulation and accentuate the pro- and diagnostic potential of
ADAM15 in vascular disease and cancer.
Main collaborators
Professor Terho Lehtimäki, Tampere University Hospital, Finland; Professor Kalle Saksela, Haartman Institute, University of
Helsinki, Finland; Professor Anthony Turner, IMCB, University of Leeds, UK; Professor Markku Pelto-Huikko, University of
Tampere Medical School, Finland; Dr. Hannu Haapasalo, Dept. of Pathology, Tampere University Hospital, Finland.
Funding
The Medical Research Fund of Tampere University Hospital
Personnel
Group Leader:
PhD Student:
22
Annual Report 2010
Ari-Pekka Huovila, PhD
Iivari Kleino, PhD
Rebekka Ortiz, MD
Paula Koskela
23
Biochemistry of Cell Signaling
The mammalian p21-activated kinases (PAKs) 1-3 act as downstream effectors of the small GTPases Cdc42 and Rac1
and play important roles in the regulation of the actin cytoskeleton morphology, the transduction of signals controlling
gene expression, and the execution of programmed cell death. The roles of PAKs in these pivotal cellular processes have
directed significant attention to understanding how the activity of these serine/threonine kinases is controlled.
The N-terminal regulatory domain of the various PAK family members contains several potential SH3-domain binding
PxxP-motifs, some of which have been found to play important roles in the activation and cellular localization of the
kinases. We have screened a proteome-wide phage-display library to identify all SH3-domains binding to PAK1-3. From
this screen we have identified several new PAK-interacting proteins, among which are POSH2 and all members of the
vinexin protein family. We are currently studying the roles of these interactions in different PAK functions.
Main collaborators
Professor Kalle Saksela, University of Helsinki, Finland; Professor Ole Nørregaard Jensen, University of Southern
Denmark, Denmark
Funding
The Academy of Finland, the Medical Research Fund of Tampere University Hospital.
Personnel
Group Leader:
Herma Renkema, PhD
Marita Hiipakka, PhD
PhD Students:
Hanna Polari, MSc
Satu Kärkkäinen, MSc
Laboratory staff:
24
Mitochondria
FinMIT’s research groups aim to derive new knowledge about the
structure, function and regulation of mitochondria, and use this to develop
novel strategies for therapy of mitochondrial disorders.
Kristina Lehtinen, Technician
Annual Report 2010
25
Mitochondrial Gene Expression and Disease
Mitochondrial Biogenesis in Health and Disease
Defects in the mitochondrial OXPHOS system cause a wide variety of human diseases, ranging from fatal infantile disorders to
neurodegenerative pathologies of old age, also including a substantial proportion of cases of common conditions, such as deafness,
diabetes, epilepsy, and cardiomyopathy. We are engaged in a long-term effort to identify at the molecular level the pathological
mechanisms associated with these disorders, aiming to use this knowledge to design effective therapeutic interventions.
Research in our lab is centered on studies of mitochondrial biogenesis in health and disease. Our focus is on mitochondrial DNA
transactions, which represent the first phase of the mitochondrial life cycle. We use a multi-disciplinary strategy to study mtDNA
replication and transcription, and their regulation by nuclear-mitochondrial communication, including biochemical, molecular
genetic, structural and computational approaches to understand enzyme and protein function in both human and Drosophila
systems. We translate our findings into biological models of mitochondrial function and dysfunction in fly cell culture and in
animals. In collaboration with Professor Howy Jacobs, we are also exploring the effects of mtDNA haplotype on mtDNA copy
number, organismal fitness and longevity.
Our effort is divided into three directions:
1. Basic studies of the mitochondrial genetic system: we are studying mitochondrial DNA (mtDNA) replication using a
combination of 2D agarose gel electrophoresis, LM-PCR and electron microscopy, combined with regulated expression of key
mtDNA-binding proteins. We have elaborated a new model for metazoan mtDNA replication involving a transient RNA
lagging strand. In human heart we have found evidence for a distinct type of mtDNA replication involving recombination, which
can be experimentally induced by several different transgenic manipulations.
2. Analysis of mitochondrial disease models in Drosophila: we are using a combination of transcriptomics, proteomics, transgenetics
and classical genetics to profile gene expression and identify target tissues, compensatory pathways and genetic and environmental
suppressors of Drosophila mutants that model OXPHOS disease in humans, focusing initially on the tko mutant, which has a
general defect in mitochondrial protein synthesis.
3. Development of a novel gene-therapy approach to mitochondrial disorders: we are testing the potential of the alternative
oxidase (AOX) from Ciona intestinalis, as well as single-subunit NADH dehydrogenases, to act as a by-pass of the cytochrome
segment of the OXPHOS system under conditions where it is deficient or malfunctioning. In both human cells and Drosophila,
AOX renders mitochondrial respiration insensitive to inhibitors such as cyanide or antimycin, diminishes the production of
toxic oxygen radicals, and complements the phenotypes of some specific OXPHOS disease mutations. Preliminary findings also
indicate intriguing effects on lifespan.
We currently have open positions for professional researchers and postdoctoral fellows in both the protein and mtDNA projects
funded by the U.S. National Institutes of Health, the Academy of Finland and the FinMit Centre of Excellence in Research
on Mitochondrial Disease and Ageing. Applicants for these positions, and interested Finnish M.Sc. and Ph.D. candidates are
welcome to submit a statement of research interests and qualifications, curriculum vitae and letters of reference to laurie.s.kaguni@
uta.fi. Opportunities area available to work both at the University of Tampere, Finland and Michigan State University, U.S.A.
Personnel
Group Leader:
PhD Student:
Laboratory staff:
Professor Laurie Kaguni
Tiina Riihimäki
Jokela Merja, Laboratory technician
Main collaborators
Group leader Ian Holt, MRC-Mitochondrial Biology, Cambridge, UK; Dr. Pierre Rustin, INSERM, Hôpital Debré, Paris, France;
Dr. Kevin O’Dell, University of Glasgow, UK; Professor Dongchon Kang, Kyushu University, Fukuoka, Japan; Professor Nils-Göran
Larsson and Aleksandra Trifunovic, Karolinska Institute, Stockholm, Sweden.
Funding
The Academy of Finland (FinMIT Centre of Excellence), the European Research Council, the Sigrid Juselius Foundation, the
Tampere University Hospital Medical Research Fund, EMBO, EU
Personnel
Group Leader:
Shanjun Chen, PhD
Giuseppe Cannino, PhD
Eric Dufour, PhD
Atsushi Fukuoh, PhD
Priit Jöers, PhD
Alberto Sanz, PhD
Jacek Lenart, PhD
Suvi Vartiainen, PhD
PhD Students:
Anne Hyvärinen, MSc
Kia Kemppainen, MSc
Esko Kemppainen, MSc
26
Academy Professor Howy Jacobs, PhD
Laboratory staff:
Other staff:
Tea Tuomela, Technician
Päivi Lillsunde, Technician
Bettina Hutz, Technician
Marja Pirinen, Technician
Essi Kiviranta, Technician
Marika Vähä-Jaakkola, Technician
Rhoda Stefanatos, Research Assistant
Päivi Manninen, Project Manager
Matti Lakanmaa
Marie Chalons
Lucile Boyer
Angela Wilson, Erasmus-student
Kirsty Allan
Anna Popplestone
Akbar Zeb
Annual Report 2010
27
Mitochondrial Gerontology and Age-related Diseases Group
Ageing is a universal process of degeneration that impairs the capacity of an individual to cope with stress. We aim to understand
how this ageing occurs in order to delay this process and prolong healthy lifespan. Recently it has emerged that mitochondria
play a critical role in the regulation of ageing. We utilize the power of Drosophila genetics in combination with various cellular,
biochemical and physiological approaches to manipulate mitochondrial function and increase maximum lifespan. This approach
should prolong healthy lifespan and delay ageing-related diseases (cardiovascular disease, cancer, arthritis, cataracts, osteoporosis,
type 2 diabetes, Alzheimer’s disease).
Main collaborators
Professor Christiaan Leeuwenburgh, University of Florida (USA), Dr. Daniel Fernandez-Ayala, Pablo Olavide University (Spain),
Professor Howy Jacobs, University of Tampere (Finland), Professor Reinald Pamplona, University of Lleida (Spain) and Dr.
Ricardo Gredilla, Complutense University of Madrid (Spain)
Funding
The European Research Council, the Medical Research Fund of Tampere University Hospital (EVO)
Personnel
Group Leader:
Other staff:
Alberto Sanz, PhD
Mohan Aravind Kumar
Essi Kiviranta, Research assistant
Mitochondrial DNA Maintenance Group
FinMIT Centre of Excellence, Tampere, Finland
Institute for Genetic and Metabolic Disease, Radboud University Nijmegen, the Netherlands
Apart from a few well characterized proteins, little is known about the molecular mechanisms involved in mitochondrial DNA
(mtDNA) organization, replication and repair. As part of ongoing research, several years ago we identified a new mitochondrial
protein called Twinkle. It was shown that mutations in the gene for Twinkle, in families of several ethnic origins including one
Finnish family, are associated with a late onset disorder: autosomal dominant Progressive External Opthalmoplegia (adPEO). In
addition, the mitochondrial DNA polymerase POLG has been recognized as an adPEO disease gene. AdPEO is characterized by
the accumulation of mtDNA deletions in the brain and skeletal muscle, and is clinically identified by ophthalmoparesis and exercise
intolerance, but can also show other variable phenotypes. Other adPEO genes remain to be identified.
Our research pursues a better understanding of the role of Twinkle in human disease, identification of new components of the
mtDNA maintenance machinery, and to better understanding of the processes of mtDNA maintenance in both health and disease.
More specifically, the research aims are to:
1. Elucidate the enzymatic and cellular effects of Twinkle adPEO mutations and to establish the functions of Twinkle in mtDNA
metabolism and organization
2. Systematically identify new proteins involved in mtDNA maintenance using various approaches, including biochemical
isolation of mitochondrial DNA/protein complexes
3. Functionally characterize newly identified proteins involved in mtDNA maintenance
4. Understand the dynamics of mitochondrial gene segregation at the cell biology level.
Main collaborators
Professor Anu Wartiovaara, Biomedicum Helsinki, Finland; Group leader Ian Holt, MRC-Mitochondrial Biology, Cambridge, UK;
Professor Howy Jacobs, University of Tampere, Finland; Professor Eric Verdin, UCSF, USA.
Funding
The Academy of Finland, EVO, IMT, the Netherlands Organization for Scientific Research (NWO)
Personnel
Group Leader:
PhD Students:
Hans Spelbrink, PhD (Nijmegen, Tampere)
Lucia Valente, PhD (Nijmegen)
Joachim M. Gerhold, PhD (Nijmegen)
Nina Rajala, PhD student (Tampere)
Fenna Hensen, PhD student (Nijmegen)
Sirin Cansiz, PhD student (Nijmegen)
Alexey Klymov, MSc. student (Nijmegen)
Mai Nguyen, BSc. student (Nijmegen)
Laboratory staff:
Merja Jokela, technician (Tampere)
Outi Kurronen, technician (Tampere)
Helga van Rennes, technician (Nijmegen)
Home page: http://www.ncmd.nl/page/309/mitochondrial-dna-maintenance.htm
28
Annual Report 2010
29
Genetic Immunology
It takes several days or even weeks for our immune system to develop a specific immune response. Nevertheless, most of us stay
alive, and often healthy, thanks to an elaborate system of rapidly activated innate immune defenses. Work on insects and other
invertebrates that lack an acquired immune response has played an important role for the progress of this field. Our research group
has developed Drosophila as a useful model system to study innate immunity. The insight that immune reactions in insects are closely
related to the human innate immune defense has led to a rapidly growing interest in this model in recent years. In addition, insect
immunity is of intrinsic interest because insects are vectors for serious human disease, and because insect pathogens are increasingly
used to control agricultural pests.
The immune response in Drosophila includes both humoral and cellular components. The humoral response is manifest in the
production of potent antimicrobial peptides. The molecular mechanisms of this response have been investigated intensely and are
now reasonably well understood. By contrast, much less is known about the cellular part of this immune system, which is capable
of relatively sophisticated functions such as the recognition, encapsulation and killing of parasites, and the phagocytosis of bacteria.
Molecular immunology
The aim of the molecular immunology groups is to reveal the basic
mechanisms that regulate immune response and to use this
information to develop novel therapeutic or preventive strategies.
Over the years, our laboratory in Umeå, Sweden, has engaged in fruitful collaboration with the laboratory of Prof. Mika Rämet
in Tampere. A FiDiPro grant from the Academy of Finland made it possible for us to set up a laboratory at IMT, and thereby
intensifying the collaboration with the Rämet laboratory as well as with Prof. Olli Silvennoinen and others at IMT. During 2010, we
recruited more co-workers and set up new projects. Our work is conducted in close collaboration with the recently set-up Biocenter
Finland -funded Drosophila core facility (http://cofa.uta.fi/drosophila_index.php).
Main collaborators
Professor Istvan Ando, Biological Research Center, Hungarian Academy of Science, Szeged, Hungary; Professor Ronald van Rij,
Radboud University, Nijmegen, the Netherlands; Professor Andrew G. Clark, Cornell University, USA; Professor Todd Schlenke,
Emory University, USA; Professor Jay Evans, USDA-ARS, USA; Professor Thomas Kieselbach, Department of Chemistry, Umeå
University, Sweden; Professor Gunnar Wingsle, Umeå Plant Science Centre, Sweden; Professor Ruth Palmer, Department of
Molecular Biology, Umeå University, Sweden; Professor Mika Rämet, Institute of Medical Technology, University of Tampere,
Finland.
Funding
The Academy of Finland, the Swedish Research Council, the Swedish Cancer Society.
Personnel
Group Leader:
PhD Students:
Laboratory staff:
30
Annual Report 2010
Professor Dan Hultmark, Ph.D.
Anni Kleino, Ph.D.
Ines Anderl, Dipl. Biol.
Volker von Gernler, Dipl. Biol.
Sina Saari
Otto Mäkelä
Tuula Myllymäki
31
Immunoregulation
Experimental Immunology
Our group investigates the regulative mechanisms of immune cells with special deference to on the role of proprotein convertases
(PC). PCs cleave and convert immature proproteins into functional end products. We have previously shown that the expression
of a PC family member furin is highly regulated in immune cells and its expression in T cells is critical for the maintenance of
peripheral immune tolerance. Moreover, our results indicate that furin is essential for Th1 type cell-mediated immunity and adequate
development of immune cells.
Most important physiological mechanisms are conserved in evolution, and therefore it is possible to use genetically tractable model
organisms such as the fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio) to study genetic diseases, and also complex
diseases like cancer, cardiovascular diseases or diabetes. Our research group uses fruit flies and zebrafish in order to investigate the
immune response mechanisms.
Flies have a highly effective innate immune response. In contrast to mammals, Drosophila has no adaptive i.e. antibody-mediated
immunity, which makes it a valid model for studying the pattern recognition receptors and signaling pathways of innate immunity.
The conservation between the most important immunity signaling pathways in Drosophila (Toll, Imd and JAK/STAT pathways) and
the human pathways mediating inflammation (IL-1/TLR, TNF and JAK/STAT) is especially striking. We have used Drosophila
as a model to discover novel classes of gene products that are important in combatting pathogens mainly by using an in-house
developed RNA interference (RNAi) -based in vitro screening method in Drosophila S2 cells (Rämet et al. (2002) Nature). This
screening method has been utilized on genome-wide scale to study the functional significance of gene products for numerous cell
based functions using our unique collection of dsRNAs covering the entire Drosophila genome. In recent years we have used this
collection successfully to identify new proteins necessary for: 1.) recognition and phagocytosis of bacteria (Rämet et al., 2002 Nature;
Kocks et al., 2005 Cell; Ulvila et al., 2011 J Leukoc Biol); 2.) the RNAi phenomenon itself (Ulvila et al., 2006 JBC) 3.) NF-kappaB
signaling (Kleino et al., 2005 EMBO Journal; Kleino et al., 2008 J Immunol, Valanne et al., 2010 J Immunol) and 4.) JAK/STAT
signaling (Kallio et al., 2010 FASEB J).
In addition to the Drosophila model, we have established a state-of-the-art zebrafish facility in order to carry out large-scale genetic
screens in zebrafish. The zebrafish has recently emerged as a powerful model for infectious diseases and immune function. As a
vertebrate, it is evolutionarily relatively close to humans and has a fully developed immune system. Compared with other vertebrate
models zebrafish are small, fast-growing, inexpensive and easy to manipulate genetically. These characteristics make it possible to
carry out large-scale mutagenesis screens or to create extensive infection models using the zebrafish model. Mycobacterium marinum, a
close relative of M. tuberculosis, is used widely as a model to study M. tuberculosis pathogenesis. It causes a granulomatous, tuberculosislike disease in zebrafish and leads to both innate and adaptive immune responses. We study the genetic networks underlying the
mechanisms of innate and adaptive immune responses in mycobacterial infections by forward genetic analysis in the zebrafish model.
Secondly, we are developing a mycobacterial vaccination model in the zebrafish system.
See: Biocenter Finland Funded Core Facilities on page 11.
In the future we shall continue to explore the molecular mechanisms of furin in T cells and its role as a regulator of immune
homeostasis. We are also interested in how PC family members may contribute to the pathogenesis of immune-mediated diseases,
such as autoimmunity or allergy. In addition, we want to understand how PCs regulate hematopoiesis and contribute to the host
defense against diverse pathogens.
The Immunoregulation Group was founded in 2009 and currently consists of three postdoctoral fellows, two technicians and one
PhD student. We have expertise in the methodology that is essential for analyzing immune cell function including primary cell
cultures, flow cytometry, cytokine measurements and T regulatory cell suppression assays.
Main collaborators
Scientific Director John O’Shea (NIAMS/NIH, USA), Group Leader John Creemers (University of Leuven, the Netherlands),
Professor Mika Rämet (University of Tampere, Finland), Group Leader, Head of Proteomics Garry Corthals (University of Turku,
Finland), Docent Panu Kovanen (University of Helsinki, Finland)
Funding
The European Union, the Academy of Finland, the Medical Research Fund of Tampere University Hospital (EVO), the Sigrid
Juselius Foundation, the Emil Aaltonen Foundation.
Personnel
Group Leader:
Researchers:
Laboratory staff:
Main collaborators
Marko Pesu, PhD
Kati Pulkkinen, PhD
Hannu Turpeinen, PhD
Zsuzsanna Ortutay, PhD
Professor Dan Hultmark, Umeå University, Sweden & Institute of Medical Technology, University of Tampere, Finland, Professor
Christine Kocks, Harvard Medical School, USA, Professor Ylva Engström, Stockholm University, Sweden, Professor Mikko
Hallman, University of Oulu, Finland, Professor Olli Silvennoinen, Institute of Medical Technology, University of Tampere, Finland.
Zuzet Martinez Cordova, MSc
Anna Oksanen, BSc
Funding
Sanna Hämäläinen, laboratory technician
Annemari Latvala, laboratory technician
The Academy of Finland, the Sigrid Juselius Foundation, the Competitive Research Funding of Pirkanmaa Hospital District (EVO),
the Foundation for Pediatric Research, the Emil Aaltonen Foundation, the Tampere Tuberculosis Foundation
Personnel
Group Leader:
PhD Students:
32
Annual Report 2010
Professor Mika Rämet MD, PhD
Susanna Valanne, PhD
Mataleena Parikka, DDS, PhD
Jinghuan Wang, PhD
Johanna Ulvila, PhD (University of Oulu)
Anni Kleino, MSc
Jenni Kallio, MSc
Henna Myllymäki, MSc
Leena-Maija Vanha-aho, MSc
Sanna-Kaisa Harjula, MSc
Marika Lahtinen, MSc
Laboratory staff:
Kaisa Oksanen
Milka Vuoksio
Meri Kaustio
Anni Järvinen
Elina Pajula
Nick Halfpenny
Leena Mäkinen
Matilda Martikainen
Tuula Myllymäki
33
Molecular Immunology - Cytokine Receptor Signaling
Cytokines regulate the growth and differentiation of hematopoietic cells through the activation of JAK tyrosine kinases and STAT
transcription factors. Deregulated activation of the JAK/STAT pathway has been implicated in human diseases, particularly in cancer,
hematological disorders, allergies and autoimmune diseases. An understanding of the mechanisms of JAK/STAT activation at the
molecular and atomic level will provide the molecular basis for designing intervention strategies and methodologies for the screening
and development of therapeutic compounds. Our research projects focus on structure/function analysis and posttranslational
modifications of the JAK/STAT pathway.
Aberrant activation of JAK kinases, e.g. by point mutations or translocations, lead to cellular transformation and cancer. Point
mutations in the JH2 (pseudokinase) domain of JAK2 cause Polycytemia Vera and other myeloproliferative diseases. Our laboratory
has conducted pioneering work in characterizing the function of JH2 in regulation of JAK kinases, and the disease causing mutations
in JAK2 and JAK3 localized in the inhibitory region identified previously in our studies. Present works defines the molecular
mechanism of JH2 mediated JAK regulation during cytokine receptor activation, and aim at characterizing JAKs at the structural
level. In collaboration with Professor Mika Rämet We are also investigating novel regulators of JAK-STAT signaling identified in a
genome wide screen.
We are investigating the molecular mechanisms of STAT mediated gene regulation. STAT6 plays a decisive role in allergic responses,
and we adopted a combined biochemical and structural approach to analyze the composition, structure and function of the STAT6
enhanceosome. Through a direct proteome approach we have identified transcriptional coregulators for STAT6. The first of the
regulators identified, Tudor-SN (p100/SND1), was found to participate in several aspects of cellular RNA metabolism, and to
function both as an interaction surface for transcription factors and in pre-mRNA processing via the so-called Tudor domain (TD).
In collaboration with Dr J. Liu we have crystallized the TD of Tudor-SN allowing detailed analysis of the TD function. Recently in
collaboration with P. Botzhkov we also identified a novel function of Tudor-SN in regulation of apoptosis. Current studies focus on
gaining an in-depth understanding of the Tudor-SN function as an RNA-binding protein and regulator of gene expression using
Next-Generation Sequencing technologies and Tudor-SN knockout mouse model.
Affiliated groups
The affiliated groups have focused their research on cell physiology
and molecular pathogenic mechanisms of certain diseases,
such as coeliac disease and cancer.
Main collaborators
Professor S. Hubbard, NYU Medical School, USA; Professor O.N. Jensen, University of Southern Denmark, Denmark; Professor H.
Alenius, Finnish Institute of Occupational Health, Finland and EU FP6 Marie Curie RTN on Cytokine Receptors in Disease; Dr.
J. Yang, Tianjin Medical University, China
Funding
The Academy of Finland, the Sigrid Juselius Foundation, the Pirkanmaa Hospital District, the Finnish Funding Agency for
Technology and Innovation (TEKES)
Personnel
Group Leader:
PhD Students:
Laboratory staff:
Other staff:
34
Professor Olli Silvennoinen, MD, PhD
Daniela Ungureanu PhD
Juha Saarikettu, PhD
Juha Grönholm, Bachelor of Medicine
Tekele Fashe, DVM, MSc Yashavanthi Niranjan, MSc
Jie Shao, visiting PhD student
Tuija Pekkala, BSc
Paula Kosonen, Technician
Merja Lehtinen, Technician
Visiting professor Jie Yang, MD, PhD
Pia Isomäki, MD, PhD
Samuli Rouninoja, MD, PhD
Xianzhi Zhang, PhD
Annual Report 2010
35
Coeliac Disease Study Group
Tissue Biology Group
Coeliac disease (CD) is intolerance to dietary gluten present in wheat, rye and barley and belongs to the most common food related
life-long disorders in Europe and the United States. A typical feature for CD, in addition to the small intestinal mucosal changes,
is gluten dependent serum IgA class autoantibodies which are widely used in clinical practice in selecting patients to undergo
diagnostic intestinal biopsy. Although the target of these antibodies is known to be transglutaminase 2 (TG2), the role of these
autoantibodies in CD pathogenesis is far from clear with the generally accepted view of CD as a T-cell-mediated disorder. Today,
the only effective treatment for CD is a life-long gluten-free diet, where wheat, rye and barley are excluded. As adhering to a strict
gluten-free diet is burdensome, new treatment options are needed.
The research in the Tissue Biology Group is focused on cellular pH homeostasis regulated by carbonic anhydrase (CA) enzymes.
The aim of our study group is to ascertain how large a proportion of the entire Finnish population suffers from gluten intolerance
and thus need to permanently exlude gluten from their daily diet in order to sustain health and general well-being and to prevent the
protean associated diseases and complications of CD. We also hope to develop more efficient, simple and non-invasive diagnostic
tools, both serology-based and genetic, that enable the identification of the vulnerable gluten-sensitive population subgroup who
already benefit from life-long gluten-free diet in the early phase of the disease process. Our group also aims to study the mechanism
behind gluten-toxicity and the role of disease-specific autoantibodies in pathogenesis. Our goal is also to eliminate the coeliac-toxic/
immunogenic fractions present in wheat, rye and barley in order to develop new coeliac-safe foods and carry out preclinical and
clinical studies of novel treatment options.
Main collaborators
The “TRACKS” Consortium, the “TRANSCOM” Consortium (Professor M. Griffin, coordinator); the ELVIRA “MANGLIN”
Consortium (Professors J. Kere, P. Männistö and P. Salovaara); Docent Päivi Saavalainen, University of Helsinki; Docent J. Partanen
and J. Mättö, the Finnish Red Cross; Professor H. Hyöty, University of Tampere; Ikihyvä project (MD, PhD L. Luostarinen);
National Public Health Institute (Professors. A. Reunanen and P. Knekt); Professor M. Hadjivassiliou, University of Sheffield, UK;
MD PhD A. Stanescu-Popp, Romania; Prof. H. Wieser, Deutsche Forschungsanstalt für Lebensmittelchemie, Garching, Germany;
Professor C. Khosla, University of Stanford, USA, Professor B. Jabri, University of Chigaco, Chigaco, USA, Dr D. Leffler, Harvard
Medical School, USA; professor P. Daugherty and Dr J. Ballew, University of California-Santa Barbara, USA; professor JR Bilbao,
University of Basque Country, Barakaldo, Spain, Professor C. Esposito, University of Salerno, Italy, Dr R. Anderson, The Walter &
Eliza Hall Institute of Medical Research (WEHI), Melbourne, Australia; Industrial collaborators: Anibiotech Oy, ChemoCentryx
Ltd., Alvine Pharmaceuticals Ltd.
Funding
The European Commission, the Academy of Finland, TEKES, the Competitive Research Funding of Pirkanmaa Hospital District,
the Paediatric Research Foundation, the Sigrid Juselius Foundation, the Research Foundation of the Finnish Coeliac Society, the
Finnish Foundation of Gastroenterological Research, the Finnish Cultural Foundation, the Finnish Medical Society Duodecim
Personnel
Group Leader:
Principal
Investigators:
PhD Students:
36
Professor Markku Mäki, MD, PhD
Docent Katri Kaukinen, MD, PhD
Docent Pekka Collin, MD, PhD
Docent Katri Lindfors, PhD
Associate professor Ilma Korponay-Szabo, MD, PhD
Sergio Caja, PhD
Marja-Leena Lähdeaho, MD, PhD
Kalle Kurppa, MD, PhD (10/2010)
Essi Myrsky, MSc/PhD (05/2010)
Satumarja Stenman, MSc
Tiina Rauhavirta, MSc
Cristina Nadalutti, MSc
Laura Airaksinen, MSc
Suvi Kalliokoski, MSc
Outi Koskinen, MD, PhD (05/2010)
Anniina Ukkola, MD
Anitta Vilppula, MD
Anitta Ruuskanen, MD
Visiting students:
Laboratory staff:
Other staff:
Annual Report 2010
Carbonic anhydrases are enzymes that catalyze the reversible hydration of carbon dioxide according to the following reaction: CO2
+ H2O ↔ HCO3- + H+. The main function of this protein family is to regulate pH homeostasis in different organisms, including
eukaryotes, bacteria and archaea. The alpha-CA gene family present in mammals includes 13 enzymatically active members. Additional
gene families are also expressed in various species other than human. These include beta-, gamma-, epsilon-, and zeta-CAs.
One major line in our research is the investigation of the distribution and functional significance of cancer-associated CA isozymes
(CA II, VII, IX and XII) in normal and pathological tissues. In these investigations, we utilize CA knockout mouse models, which are
excellent tools for physiological studies. In 2010 our group was involved in the European Union DeZnIT Consortium, which aimed
to design and produce novel inhibitor molecules against zinc enzymes including different CAs. One major task of our group was to
produce different CA isozymes as recombinant proteins for characterization and drug design studies. In 2010 we also established a
knockout mouse model of CA VI deficiency. CA VI is the only secretory isozyme of the alpha-CA gene family. The enzyme is present
in saliva and milk, and its physiological functions have been remained unclear. In a recent article, we characterized CA VI deficient
mice and described several interesting alterations in gene expression levels, which may help to understand the role of CA VI. In
the past year we also reported and characterized the first beta-CA in Drosophila melanogaster and currently aim to isolate the same
enzyme from pathogenic organisms, such as Anopheles mosquito. Our group has also extended out research to three novel members
of the alpha-CA family. Carbonic anhydrase-related proteins (CARPs) are structurally quite similar to classical CAs. The main
exception is the lack of the critical histidine residues in the active site cavity, which are important for CA catalytic activity. Therefore
CARPs are catalytically inactive, but they have other roles, especially in the central nervous system. In human and mouse cerebellum,
CARP VIII protein is linked to movement coordination. In 2010 we reported the distribution of all CARPs in mouse tissues and
phylogenetic analysis of CARPs in a number of different species. The results led us to investigate further the role of CARPs, and we
selected zebrafish as a model organism. These studies are underway in our laboratory and the first results on CARP VIII knockdown
zebrafish will be submitted for publication in near future.
Main collaborators
Professor William S. Sly, Saint Louis University School of Medicine, USA; Professors Silvia and Jaromir Pastorek, Institute of
Virology, Slovak Academy of Sciences, Slovak Republic; Professor Claudiu Supuran, Università degli Studi di Firenze, Italy;
Professor Onni Niemelä, EP Central Hospital and University of Tampere, Finland; Dr. Hannu Haapasalo, Laboratory Centre,
Tampere University Hospital, Finland; Dr. Vesa Hytönen, Institute of Medical Technology, University of Tampere, Finland.
Funding
The European Union Grant (DeZnIT), the Academy of Finland, the Sigrid Juselius Foundation, the Medical Research Fund of
Tampere University Hospital.
Satu Korpimäki
Sampsa Kinos
Olli Lauronen
Ida Lahtinen
Pilvi Paarlahti
Asif Rasheed
Jaakko Salminiemi
Juha Taavela
Boglarka Toth
Jennifer Cullighan
Personnel
Kaija Laurila, MSc, Head of Laboratory
Jorma Kulmala, Technician
Mervi Himanka, Tecnician
Soili Peltomäki, Technician
Anne Heimonen, Technician
Kaija Kaskela, Project secretary
Marja-Terttu Oksanen, Research nurse
Group Leader:
PhD Students:
Laboratory staff:
Professor Seppo Parkkila, MD, PhD
Peiwen Pan, PhD
Ashok Aspatwar, PhD
Piritta Hynninen, MD
Joonas Haapasalo, MD
Martti Tolvanen, Phil. lic.
Fatemeh Ahmad, MSc
Heini Kallio, MSc
Leo Syrjänen
Anna Lappalainen
Anna-Kaisa Harju
Aulikki Lehmus, Technician
Marianne Kuuslahti, Technician
37
The Biotechnology Program
Master’s Degree Program in Bioinformatics
Since 2001 the Biotechnology Program at the Institute of Medical Technology has been offering interdisciplinary BSc and MSc
degrees. The fundamental objective of the Program is to educate a new generation of young scientists with outstanding theoretical
knowledge and state-of-the-art research skills to harness the potential of biosciences for the development of wellbeing. Special
emphasis is placed on the biomedical branch of biotechnology, which can be considered one of the core areas of the research conducted
in IMT. The Program has increasingly intensive collaboration with Tampere University of Technology, and vital international
ERASMUS exchange of students and teacher mobility with the University of Glasgow in Scotland and the National University
of Ireland in Galway. In addition it has educational contacts with the national biotechnology industry and is engaged with various
departments at the University of Tampere in interdisciplinary teaching. Teaching is mostly provided by the Program staff with the
help of other IMT academic personnel and educational partners. Annual intake is 25-30 students. The majority of the funding comes
from the University budget and complementary funding has been received from the BioneXt Project by the City of Tampere.
The Master’s Degree Program in Bioinformatics is co-operative joint operation between our Institute and the Department of
Information Technology at the University of Turku. The program was launched in 2006, and was the first international master’s degree
program in bioinformatics in Finland. This program aims at imparting interdisciplinary knowledge of bioinformatics, and the joint
expertise of the participating institutions has been essential in arranging the courses. All teaching is given in English, and the students
learn to work together with associates from different countries and different scientific backgrounds. Instruction takes advantage of
modern technology, for example web courses, video lectures, and video conferencing, in addition to traditional contact teaching.
After completing the BSc degree, the students enter advanced studies where they have a choice of the four fields of specialization:
1) Molecular biology
2) Bioinformatics
3) Cell and tissue technology
4) Biobusiness
In the first nine years of the Program nearly 60 students graduated and the great majority of them have found placements academic
research, industrial R&D and marketing or teaching. Several students have continued their postgraduate studies abroad prestigious
research institutions, e.g. EMBL in Heidelberg, Germany, and the University of Cambridge, UK. The rapid development and success
of the Program is based on the devoted staff and well-motivated students. The Program provides a firm foundation for further
development and continuing success in the future, due to the closer and more intensive educational collaboration with the Tampere
University of Technology.
Students are required to have a bachelor degree or equivalent in biosciences or information technology, or in other relevant
method sciences, such as statistics. The studies encompass different aspects of bioinformatics, computer science, information
technology and biosciences, including biochemistry, genetics, and molecular biology. After preliminary courses which provide
background information when needed, the students take the courses together. At the end of their studies, students are able combine
knowledge of information technology and biosciences to accomplish complex analysis and data mining tasks of biological data.
The program has been running successfully. Student enrolment has been organized annually with an intake of 15 students per university. .
Teaching staff:
Professor Mauno Vihinen, PhD
Csaba Ortutay, PhD, Docent in Bioinformatics
Senior Research Associate Martti Tolvanen, Ph.Lic.
Present staff of the Biotechnology Program:
Professor Markku Kulomaa PhD
Professor Anne Kallioniemi, MD, PhD
University Lecturer Olli Jaakkola, PhD
Senior Research Associate Ari Huovila, PhD
Senior Research Associate Jarkko Valjakka, PhD
Senior Research Associate Martti Tolvanen, MSc
Lecturer Helena Torkkeli, PhD, MBA
Laboratory techinican Janette Hinkka
Coordinator Marjatta Viilo, MSocSc
Administrator Riitta Aallos, MA
Study Secretary Mira Pihlström, MSocSc
Master’s theses at the Master’s Degree Program in Bioinformatics
Master’s theses at the Biotechnology Program
Niskanen Ville - Selvitys nonkliinisen tutkimuspalvelukokonaisuuden
luomisesta Tampereen alueelle (31.12.2010)
Tirkkonen Laura - The effects of vibration loading on adipose stem
cell viability, proliferation and osteogenic differentiation (10.6.2010)
Kotha Sreevani Analysis of missense mutations in adenosine deaminase
using Pathogenic-Or-Not-Pipeline (PON-P) (20.12.2010)
Kuivanen Juuso - Engineering of Saccharomyces cerevisiae for
carboxylic acid production (31.11.2010) Kukkola Saija - HLA-DQ2-geenien promoottorialueiden metylaatio
keliakiassa (3.6.2010)
Nair Preethy Codon usage bias of the overlapping genes in microbial
genomes (3.11.2010)
Airaksinen Laura - Kaura ja keliakia - kauraperäisten molekyylien
hyödyt ja haitat in vitro (29.11.2010) Kukkola Saara - The effect of androgen receptor overexpression on its
recruitment to the regulatory regions of PSA and TMPRSS2 genes
(7.5.2010)
Teku Gabriel Transcriptional regulation of bidirectional promoters: role
of NF-Y (1.4.2010)
Kärkkäinen Pauliina - Nucleolar proteomics in acute leukaemia
(24.11.2010)
Mustalahti Eero - Expression and purification of endoplasmic
reticulum-targeted hydrophobin fusions in Nicotiana benthamiana and
Trichoderma reesei (28.10.2010)
Patrikainen Mimmi - HNF1B-geenin karakterisointi suomalaisissa
eturauhassyöpäperheissä (12.8.2010)
38
Laurila Kirsti - In silico analysis of point mutation effects on
transcription factor binding and protein subcellular localization
(26.4.2010)
Dai Xiaofeng A joint finite mixture model for clustering genes from
beta, Gaussian and Bernoulli distributed data (7.1.2010)
Kotipelto Tapio - Steroidihormonien molekulaarinen tunnistus
proteiineilla (26.2.2010)
Mäntymaa Anne - The effects of hypoxic condition on the
chondrogenic differentiation of adipose stem cells (12.2.2010)
Annual Report 2010
39
Tampere Graduate Program in Biomedicine and Biotechnology (TGPBB)
Dissertations 2010 in TGPBB
The first graduate school at the Institute of Medical Technology (IMT) was established in 1995. After a series of organizational
changes, the Tampere Graduate School in Biomedicine and Biotechnology (TGSBB) was officially founded in 2003 (name changed
in 2010 to its present form: TGPBB). Today TGPBB consists of students from IMT, the Medical School, Regea Institute for
Regenerative Medicine and Tampere University of Technology (TUT). The board of TGPBB consists of representatives from IMT,
Regea Institute for Regenerative Medicine and the Faculty of Medicine as well as a PhD student member.
Kati Pulkkinen
HIV-1 Nef protein and the Nef-associating kinase PAK2 in cell
signaling
http://acta.uta.fi/teos.php?id=11295
Supervised by Kalle Saksela
5.2.2010
The mission of TGPBB is to provide excellent quality graduate training in biosciences, especially in the disciplines of molecular
biology, biomedicine, biotechnology, and bioinformatics. TGPBB aims to equip graduate students with high standard academic
skills that allow them to pursue successful careers, e.g. in science, medicine or biotechnology. TGPBB is genuinely committed
to the goals set by the Ministry of Education for graduate training. These include active development of professional research
careers, improved planning of dissertation work, clarification and strengthening of the responsibilities of supervisors, enhancement of
national and international collaboration, and finally, the generation of high quality PhD dissertations within a 4-year training period.
A wide variety of seminars and courses is offered and students are also actively encouraged to participate in other local, national and
international training courses, for example those organized by the Finnish Graduate School Network in Life Sciences (FinBioNet).
An important part of TGPBB is the financial support that the School provides for students to attend training courses and scientific
meetings.
The Director and the Board of TGPBB are responsible for the successful implementation of the mission of the school and are
in charge of student selection and the development of a high quality curriculum. Currently, there are 34 research groups with 49
professor or docent level dissertation supervisors enrolled in TGPBB and approximately 80 registered students are working towards
a doctoral degree in TGSBB affiliated laboratories. In 2010, TGPBB had a total of 20 graduate student positions funded by the
Ministry of Education to support full-time graduate research.
Additional information on TGPBB can be found at http://www.uta.fi/ibt/tgpbb
Director of TGPBB
Professor Johanna Schleutker
TGPBB board (since 1.3.2009-)
Professor Anne Kallioniemi, IMT
Professor Hans Spelbrink, IMT
Professor Pekka Karhunen, Faculty of Medicine
Professor Mikko Hurme, Faculty of Medicine
Academy Research Fellow Heli Skottman, Regea
Graduate student Alfonso Urbanucci, IMT
Määttä Juha
Structural and Functional Characterization of Engineered Avidin Proteins
Supervised by Markku Kulomaa and Vesa Hytönen
11.6.2010
Anni Kleino
The Imd pathway-mediated immune response in Drosophila
Supervised by Mika Rämet
23.6.2010
Janita Thusberg
Molecular effects of missense mutations - Bioinformatics analysis of genetic defects
Supervised by Mauno Vihinen
2.7.2010
Coordinator of TGPBB
Henna Mattila, PhD
40
Sofia Khan
Mutational effects on protein structures: Knowledge gained from
databases, predictions and protein models
Supervised by Mauno Vihinen
8.2.2010
Annual Report 2010
Kati Waltering
Androgen receptor signaling pathway in prostate cancer
Supervised by Tapio Visakorpi
10.9.2010
Sanna Pakkanen
Profiling of High-risk Prostate Cancer Families in Finland
Supervised by Teuvo Tammela and Johanna Schleutker
12.11.2010
Anne Hyvärinen
Functional analysis of the MTERF protein family in cultured
human cells
Supervised by Howard T. Jacobs
20.11.2010
Katri Köninki
HER-2 positive breast cancer - molecular and epidemiological
studies
Supervised by Jorma Isola
2.12.2010
Riina Kuuselo
MED29 possesses a complex role in pancreatic cancer
http://acta.uta.fi/teos.php?id-11394
Supervised by Anne Kallioniemi and Ritva Karhu
17.12.2010
41
Bioinformatics
Cancer Biology
Kohonen-Corish MR, Al-Aama JY, Auerbach AD, Axton M,
Barash CI, Bernstein I, Béroud C, Burn J, Cunningham F, Cutting GR, den Dunnen JT, Greenblatt MS, Kaput J, Katz M,
Lindblom A, Macrae F, Maglott D, Möslein G, Povey S, Ramesar R, Richards S, Seminara D, Sobrido MJ, Tavtigian S, Taylor
G, Vihinen M, Winship I, Cotton RG,
How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010.
Hum Mutat 2010 ;31(12)1374-81
Tuominen VJ, Ruotoistenmäki S, Viitanen A, Jumppanen M,
Isola J
ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67.
Breast Cancer Res 2010 ;12(4)R56
Laurila K, Vihinen M
PROlocalizer: integrated web service for protein subcellular localization prediction.
Amino Acids 2010 ;
Lanzi G, Ferrari S, Vihinen M, Caraffi S, Kutukculer N, Schiaffonati L, Plebani A, Notarangelo LD, Fra AM, Giliani S
Different molecular behavior of CD40 mutants causing hyperIgM syndrome.
Blood 2010 ;116(26)5867-74
Khan S, Vihinen M
Performance of protein stability predictors.
Hum Mutat 2010 ;31(6)675-84
Howard HJ, Horaitis O, Cotton RG, Vihinen M, Dalgleish R,
Robinson P, Brookes AJ, Axton M, Hoffmann R, Tuffery-Giraud S
The Human Variome Project (HVP) 2009 Forum “Towards Establishing Standards”.
Hum Mutat 2010 ;31(3)366-7
Ortutay, C., Olatubosun, A., Parkkila, S., Vihinen, M., and Tolvanen, M. An evolutionary analysis of insect carbonic anhydrases.
(2010) Adv. Med. Biol., Vol. 7, 145-168.
Protein Dynamics
Huhti L, Blazevic V, Nurminen K, Koho T, Hytönen VP, Vesikari T
A comparison of methods for purification and concentration of
norovirus GII-4 capsid virus-like particles.
Arch Virol 2010 ;155(11)1855-8
Syrjänen L, Tolvanen M, Hilvo M, Olatubosun A, Innocenti A,
Scozzafava A, Leppiniemi J, Niederhauser B, Hytönen VP, Gorr
TA, Parkkila S, Supuran CT
Characterization of the first beta-class carbonic anhydrase from
an arthropod (Drosophila melanogaster) and phylogenetic analysis of beta-class carbonic anhydrases in invertebrates.
BMC Biochem 2010 ;1128
42
Saarilahti K, Bono P, Kajanti M, Bäck L, Leivo I, Joensuu T,
Isola J, Mäkitie AA
Phase II prospective trial of gefitinib given concurrently with
cisplatin and radiotherapy in patients with locally advanced head
and neck cancer.
J Otolaryngol Head Neck Surg 2010 ;39(3)269-76
Köninki K, Barok M, Tanner M, Staff S, Pitkänen J, Hemmilä P,
Ilvesaro J, Isola J
Multiple molecular mechanisms underlying trastuzumab and lapatinib resistance in JIMT-1 breast cancer cells.
Cancer Lett 2010 ;294(2)211-9
Parkkila S, Lasota J, Fletcher JA, Ou WB, Kivelä AJ, Nuorva K,
Parkkila AK, Ollikainen J, Sly WS, Waheed A, Pastorekova S,
Pastorek J, Isola J, Miettinen M
Carbonic anhydrase II. A novel biomarker for gastrointestinal
stromal tumors.
Mod Pathol 2010 ;23(5)743-50
Staff S, Isola J, Jumppanen M, Tanner M
Aurora-A gene is frequently amplified in basal-like breast cancer.
Oncol Rep 2010 ;23(2)307-12
Joensuu G, Joensuu T, Nokisalmi P, Reddy C, Isola J, Ruutu M,
Kouri M, Kupelian PA, Collan J, Pesonen S, Hemminki A
A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer.
Int J Radiat Oncol Biol Phys 2010 ;78(1)42-9
Tuominen VJ, Isola J
Linking whole-slide microscope images with DICOM by using
JPEG2000 interactive protocol.
J Digit Imaging 2010 ;23(4)454-62
Cancer Genomics
Kallioniemi A
DNA copy number analysis on tissue microarrays.
Methods Mol Biol 2010 ;664127-34
Wolf M, Korja M, Karhu R, Edgren H, Kilpinen S, Ojala K,
Mousses S, Kallioniemi A, Haapasalo H
Array-based gene expression, CGH and tissue data defines a
12q24 gain in neuroblastic tumors with prognostic implication.
BMC Cancer 2010 ;10181
Annual Report 2010
Alarmo EL, Kallioniemi A
Bone morphogenetic proteins in breast cancer: dual role in tumourigenesis?
Endocr Relat Cancer 2010 ;17(2)R123-39
Kuuselo R, Simon R, Karhu R, Tennstedt P, Marx AH, Izbicki
JR, Yekebas E, Sauter G, Kallioniemi A
19q13 amplification is associated with high grade and stage in
pancreatic cancer.
Genes Chromosomes Cancer 2010 ;49(6)569-75
Ketolainen JM, Alarmo EL, Tuominen VJ, Kallioniemi A
Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic
protein 4.
Breast Cancer Res Treat 2010 ;124(2)377-86
Genetic Predisposition to Cancer
Nurminen R, Wahlfors T, Tammela TL, Schleutker J
Identification of an aggressive prostate cancer predisposing variant at 11q13.
Int J Cancer 2010 ;
Christensen GB, Baffoe-Bonnie AB, George A, Powell I, Bailey-Wilson JE, Carpten JD, Giles GG, Hopper JL, Severi G,
English DR, Foulkes WD, Maehle L, Moller P, Eeles R, Easton D, Badzioch MD, Whittemore AS, Oakley-Girvan I, Hsieh
CL, Dimitrov L, Xu J, Stanford JL, Johanneson B, Deutsch K,
McIntosh L, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC,
Isaacs WB, Thibodeau SN, McDonnell SK, Hebbring S, Schaid
DJ, Lange EM, Cooney KA, Tammela TL, Schleutker J, Paiss T,
Maier C, Grönberg H, Wiklund F, Emanuelsson M, Farnham
JM, Cannon-Albright LA, Camp NJ,
Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer
Genetics using novel sumLINK and sumLOD analyses.
Prostate 2010 ;70(7)735-44
Molecular Biology of Prostate Cancer
(MBPCG)
Gu L, Zhu XH, Visakorpi T, Alanen K, Mirtti T, Edmonston
TB, Nevalainen MT
Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer.
Anal Cell Pathol (Amst) 2010 ;33(2)55-9
Waltering KK, Porkka KP, Jalava SE, Urbanucci A, Kohonen PJ,
Latonen LM, Kallioniemi OP, Jenster G, Visakorpi T
Androgen regulation of micro-RNAs in prostate cancer.
Prostate 2010 ;
Pittman AM, Naranjo S, Jalava SE, Twiss P, Ma Y, Olver B,
Lloyd A, Vijayakrishnan J, Qureshi M, Broderick P, van Wezel
T, Morreau H, Tuupanen S, Aaltonen LA, Alonso ME, Manzanares M, Gavilán A, Visakorpi T, Gómez-Skarmeta JL, Houlston RS
Allelic variation at the 8q23.3 colorectal cancer risk locus functions as a cis-acting regulator of EIF3H.
PLoS Genet 2010 ;6(9)
Erkkilä T, Lehmusvaara S, Ruusuvuori P, Visakorpi T, Shmulevich I, Lähdesmäki H
Probabilistic analysis of gene expression measurements from
heterogeneous tissues.
Bioinformatics 2010 ;26(20)2571-7
Leinonen KA, Tolonen TT, Bracken H, Stenman UH, Tammela
TL, Saramäki OR, Visakorpi T
Association of SPINK1 expression and TMPRSS2:ERG fusion
with prognosis in endocrine-treated prostate cancer.
Clin Cancer Res 2010 ;16(10)2845-51
Suikki HE, Kujala PM, Tammela TL, van Weerden WM, Vessella RL, Visakorpi T
Genetic alterations and changes in expression of histone
demethylases in prostate cancer.
Prostate 2010 ;70(8)889-98
Rauhala HE, Jalava SE, Isotalo J, Bracken H, Lehmusvaara S,
Tammela TL, Oja H, Visakorpi T
miR-193b is an epigenetically regulated putative tumor suppressor in prostate cancer.
Int J Cancer 2010 ;127(6)1363-72
Biochemistry of Cell Signaling
Kärkkäinen S, van der Linden M, Renkema GH
POSH2 is a RING finger E3 ligase with Rac1 binding activity
through a partial CRIB domain.
FEBS Lett 2010 ;584(18)3867-72
Mitochondrial Gene Expression and Disease
Hyvärinen AK, Kumanto MK, Marjavaara SK, Jacobs HT
Effects on mitochondrial transcription of manipulating mTERF
protein levels in cultured human HEK293 cells.
BMC Mol Biol 2010 ;1172
Chua YL, Dufour E, Dassa EP, Rustin P, Jacobs HT, Taylor CT,
Hagen T
Stabilization of hypoxia-inducible factor-1alpha protein in hypoxia occurs independently of mitochondrial reactive oxygen
species production.
J Biol Chem 2010 ;285(41)31277-84
43
Jiménez-Menéndez N, Fernández-Millán P, Rubio-Cosials A,
Arnan C, Montoya J, Jacobs HT, Bernadó P, Coll M, Usón I,
Solà M
Human mitochondrial mTERF wraps around DNA through a
left-handed superhelical tandem repeat.
Nat Struct Mol Biol 2010 ;17(7)891-3
Pohjoismäki JL, Goffart S, Taylor RW, Turnbull DM, Suomalainen A, Jacobs HT, Karhunen PJ
Developmental and pathological changes in the human cardiac
muscle mitochondrial DNA organization, replication and copy
number.
PLoS One 2010 ;5(5)e10426
Sanz A, Fernández-Ayala DJ, Stefanatos RK, Jacobs HT
Mitochondrial ROS production correlates with, but does not directly regulate lifespan in Drosophila.
Aging (Albany NY) 2010 ;2(4)220-3
Sanz A, Soikkeli M, Portero-Otín M, Wilson A, Kemppainen
E, McIlroy G, Ellilä S, Kemppainen KK, Tuomela T, Lakanmaa
M, Kiviranta E, Stefanatos R, Dufour E, Hutz B, Naudí A, Jové
M, Zeb A, Vartiainen S, Matsuno-Yagi A, Yagi T, Rustin P, Pamplona R, Jacobs HT
Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction.
Proc Natl Acad Sci U S A 2010 ;107(20)9105-10
Pohjoismäki JL, Holmes JB, Wood SR, Yang MY, Yasukawa T,
Reyes A, Bailey LJ, Cluett TJ, Goffart S, Willcox S, Rigby RE,
Jackson AP, Spelbrink JN, Griffith JD, Crouch RJ, Jacobs HT,
Holt IJ
Mammalian mitochondrial DNA replication intermediates are
essentially duplex but contain extensive tracts of RNA/DNA
hybrid.
J Mol Biol 2010 ;397(5)1144-55
Fernández-Ayala DJ, Chen S, Kemppainen E, O’Dell KM,
Jacobs HT
Gene expression in a Drosophila model of mitochondrial disease.
PLoS One 2010 ;5(1)e8549
Mitochondrial Biogenesis in Health and
Disease
Oliveira MT, Kaguni LS
Functional roles of the N- and C-terminal regions of the human
mitochondrial single-stranded DNA-binding protein.
PLoS One 2010 ;5(10)e15379
Matsushima Y, Goto Y, Kaguni LS
Mitochondrial Lon protease regulates mitochondrial DNA copy
44
number and transcription by selective degradation of mitochondrial transcription factor A (TFAM).
Makowska-Grzyska MM, Ziebarth TD, Kaguni LS
Physical analysis of recombinant forms of the human mitochondrial DNA helicase.
Methods 2010 ;51(4)411-5
Ziebarth TD, Gonzalez-Soltero R, Makowska-Grzyska MM,
Núñez-Ramírez R, Carazo JM, Kaguni LS
Dynamic effects of cofactors and DNA on the oligomeric state
of human mitochondrial DNA helicase.
J Biol Chem 2010 ;285(19)14639-47
Dallmann HG, Fackelmayer OJ, Tomer G, Chen J, WiktorBecker A, Ferrara T, Pope C, Oliveira MT, Burgers PM, Kaguni
LS, McHenry CS
Parallel multiplicative target screening against divergent bacterial replicases: identification of specific inhibitors with broad
spectrum potential.
Biochemistry 2010 ;49(11)2551-62
Palin EJ, Lesonen A, Farr CL, Euro L, Suomalainen A, Kaguni
LS
Functional analysis of H. sapiens DNA polymerase gamma spacer mutation W748S with and without common variant E1143G.
Biochim Biophys Acta 2010 ;1802(6)545-51
Oliveira MT, Garesse R, Kaguni LS
Animal models of mitochondrial DNA transactions in disease
and ageing.
Exp Gerontol 2010 ;45(7-8)489-502
Mitochondrial Gerontology and Age-related Diseases
Hiona A, Sanz A, Kujoth GC, Pamplona R, Seo AY, Hofer
T, Someya S, Miyakawa T, Nakayama C, Samhan-Arias AK,
Servais S, Barger JL, Portero-Otín M, Tanokura M, Prolla TA,
Leeuwenburgh C
Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice.
PLoS One 2010 ;5(7)e11468
Sanz A, Fernández-Ayala DJ, Stefanatos RK, Jacobs HT
Mitochondrial ROS production correlates with, but does not directly regulate lifespan in Drosophila.
Aging (Albany NY) 2010 ;2(4)220-3
Sanz A, Soikkeli M, Portero-Otín M, Wilson A, Kemppainen
Annual Report 2010
E, McIlroy G, Ellilä S, Kemppainen KK, Tuomela T, Lakanmaa
M, Kiviranta E, Stefanatos R, Dufour E, Hutz B, Naudí A, Jové
M, Zeb A, Vartiainen S, Matsuno-Yagi A, Yagi T, Rustin P, Pamplona R, Jacobs HT
Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction.
Sanz A, Stefanatos R, McIlroy G
Production of reactive oxygen species by the mitochondrial electron transport chain in Drosophila melanogaster.
J Bioenerg Biomembr 2010 ;42(2)135-42
Molecular Biology-Mitochondrial DNA
maintenance
Pohjoismäki JL, Holmes JB, Wood SR, Yang MY, Yasukawa T,
Reyes A, Bailey LJ, Cluett TJ, Goffart S, Willcox S, Rigby RE,
Jackson AP, Spelbrink JN, Griffith JD, Crouch RJ, Jacobs HT,
Holt IJ
Mammalian mitochondrial DNA replication intermediates are
essentially duplex but contain extensive tracts of RNA/DNA
hybrid.
J Mol Biol 2010 ;397(5)1144-55
Spelbrink JN
Functional organization of mammalian mitochondrial DNA in
nucleoids: history, recent developments, and future challenges.
IUBMB Life 2010 ;62(1)19-32
Genetic Immunology
Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J,
Colbourne JK, , Werren JH, Richards S, Desjardins CA, Niehuis
O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik
CG, Grimmelikhuijzen CJ, Kitts P, Lynch JA, Murphy T, Oliveira DC, Smith CD, van de Zande L, Worley KC, Zdobnov
EM, Aerts M, Albert S, Anaya VH, Anzola JM, Barchuk AR,
Behura SK, Bera AN, Berenbaum MR, Bertossa RC, Bitondi
MM, Bordenstein SR, Bork P, Bornberg-Bauer E, Brunain M,
Cazzamali G, Chaboub L, Chacko J, Chavez D, Childers CP,
Choi JH, Clark ME, Claudianos C, Clinton RA, Cree AG,
Cristino AS, Dang PM, Darby AC, de Graaf DC, Devreese
B, Dinh HH, Edwards R, Elango N, Elhaik E, Ermolaeva O,
Evans JD, Foret S, Fowler GR, Gerlach D, Gibson JD, Gilbert DG, Graur D, Gründer S, Hagen DE, Han Y, Hauser F,
Hultmark D, Hunter HC, Hurst GD, Jhangian SN, Jiang H,
Johnson RM, Jones AK, Junier T, Kadowaki T, Kamping A, Kapustin Y, Kechavarzi B, Kim J, Kim J, Kiryutin B, Koevoets T,
Kovar CL, Kriventseva EV, Kucharski R, Lee H, Lee SL, Lees
K, Lewis LR, Loehlin DW, Logsdon JM, Lopez JA, Lozado
RJ, Maglott D, Maleszka R, Mayampurath A, Mazur DJ, McClure MA, Moore AD, Morgan MB, Muller J, Munoz-Torres
MC, Muzny DM, Nazareth LV, Neupert S, Nguyen NB, Nunes
FM, Oakeshott JG, Okwuonu GO, Pannebakker BA, Pejaver
VR, Peng Z, Pratt SC, Predel R, Pu LL, Ranson H, Raychoudhury R, Rechtsteiner A, Reese JT, Reid JG, Riddle M, Robertson
HM, Romero-Severson J, Rosenberg M, Sackton TB, Sattelle
DB, Schlüns H, Schmitt T, Schneider M, Schüler A, Schurko
AM, Shuker DM, Simões ZL, Sinha S, Smith Z, Solovyev V,
Souvorov A, Springauf A, Stafflinger E, Stage DE, Stanke M,
Tanaka Y, Telschow A, Trent C, Vattathil S, Verhulst EC, Viljakainen L, Wanner KW, Waterhouse RM, Whitfield JB, Wilkes
TE, Williamson M, Willis JH, Wolschin F, Wyder S, Yamada T,
Yi SV, Zecher CN, Zhang L, Gibbs RA
Functional and evolutionary insights from the genomes of three
parasitoid Nasonia species.
Science 2010 ;327(5963)343-8
Immunoregulation
Pokrzywa M, Dacklin I, Vestling M, Hultmark D, Lundgren E,
Cantera R
Pesu M
Uptake of aggregating transthyretin by fat body in a Drosophila [T-helper cells--bandleaders of immune response].
model for TTR-associated amyloidosis.
Duodecim 2010 ;126(18)2179-87
PLoS One 2010 ;5(12)e14343
Valanne S, Myllymäki H, Kallio J, Schmid MR, Kleino A, Murumägi A, Airaksinen L, Kotipelto T, Kaustio M, Ulvila J, Esfahani SS, Engström Y, Silvennoinen O, Hultmark D, Parikka M,
Rämet M
Genome-wide RNA interference in Drosophila cells identifies
G protein-coupled receptor kinase 2 as a conserved regulator of
NF-kappaB signaling.
J Immunol 2010 ;184(11)6188-98
Experimental Immunology
Kaikkonen S, Räsänen S, Rämet M & Vesikari T.
Aichi virus infection in children with acute gastroenteritis in
Finland.
Epidemiology and Infection 2010, 138:1166-71.
Valtonen TM, Kleino A, Rämet M & Rantala MJ.
Starvation reveals maintenance cost of humoral immunity.
Evolutionary Biology 2010, 37:49-57.
Ulvila J, Hultmark D, Rämet M
RNA silencing in the antiviral innate immune defence--role of
DEAD-box RNA helicases.
Ulvila J, Hultmark D & Rämet M.
Scand J Immunol 2010 ;71(3)146-58
RNA silencing in the antiviral innate immune defense--Role of
45
DEAD-box RNA helicases.
Scandinavian Journal of Immunology 2010.; 71:146-158.
Wang JH, Valanne S & Rämet M.
Drosophila as a model for antiviral immunity.
World Journal of Biological Chemistry 2010;1(5):151-159.
Hyvärinen J, Parikka M, Sormunen R, Rämet M, Tryggvason K,
Kivirikko KI, Myllyharju J, Koivunen P
Deficiency of a transmembrane prolyl 4-hydroxylase in the zebrafish leads to basement membrane defects and compromised
kidney function.
J Biol Chem 2010 ;285(53)42023-32
Rämet M, Hallman M
Surfactant proteins and respiratory syncytial virus.
J Pediatr 2010 ;157(5)866; author reply 866-7
Kallio J, Myllymäki H, Grönholm J, Armstrong M, Vanha-aho
LM, Mäkinen L, Silvennoinen O, Valanne S, Rämet M
Eye transformer is a negative regulator of Drosophila JAK/
STAT signaling.
FASEB J 2010 ;24(11)4467-79
Grönholm J, Ungureanu D, Vanhatupa S, Rämet M, Silvennoinen O
Sumoylation of Drosophila transcription factor STAT92E.
J Innate Immun 2010 ;2(6)618-24
Löfgren J, Marttila R, Renko M, Rämet M, Hallman M
Toll-like receptor 4 Asp299Gly polymorphism in respiratory
syncytial virus epidemics.
Pediatr Pulmonol 2010 ;45(7)687-92
Rämet M
J Immunol 2010 ;184(11)6188-98
Molecular Immunology
Gao X, Ge L, Shao J, Su C, Zhao H, Saarikettu J, Yao X, Yao Z,
Silvennoinen O, Yang J
Tudor-SN interacts with and co-localizes with G3BP in stress
granules under stress conditions.
FEBS Lett 2010 ;584(16)3525-32
Kallio J, Myllymäki H, Grönholm J, Armstrong M, Vanha-aho
46
LM, Mäkinen L, Silvennoinen O, Valanne S, Rämet M
Eye transformer is a negative regulator of Drosophila JAK/
STAT signaling.
FASEB J 2010 ;24(11)4467-79
Millan S, Murray L, Metzger MH, Gasparin M, Bravi E, Mäki
M,
The prevalence of celiac disease in Europe: results of a centralized, international mass screening project.
Ann Med 2010 ;42(8)587-95
Grönholm J, Ungureanu D, Vanhatupa S, Rämet M, Silvennoinen O
Sumoylation of Drosophila transcription factor STAT92E.
J Innate Immun 2010 ;2(6)618-24
Kaukinen K, Lindfors K, Collin P, Koskinen O, Mäki M
Coeliac disease--a diagnostic and therapeutic challenge.
Clin Chem Lab Med 2010 ;48(9)1205-16
Saarikettu J, Ovod V, Vuoksio M, Grönholm J, Yang J, Silvennoinen O
Monoclonal antibodies against human Tudor-SN.
Hybridoma (Larchmt) 2010 ;29(3)231-6
Lindfors K, Mäki M, Kaukinen K
Transglutaminase 2-targeted autoantibodies in celiac disease:
Pathogenetic players in addition to diagnostic tools?
Autoimmun Rev 2010 ;9(11)744-9
Rämet M
J Immunol 2010 ;184(11)6188-98
Ruuskanen A, Kaukinen K, Collin P, Huhtala H, Valve R, Mäki
M, Luostarinen L
Positive serum antigliadin antibodies without celiac disease in
the elderly population: does it matter?
Scand J Gastroenterol 2010 ;45(10)1197-202
Coeliac Disease Study
Salmi TT, Collin P, Reunala T, Mäki M, Kaukinen K. Diagnostic
methods beyond conventional histology in coeliac disease diagnosis.Dig Liver Dis 2010;42:28-32.
Stenman SM, Lindfors K, Venäläinen JI, Hautala A, Männistö
PT, Garcia-Horsman JA, Kaukovirta-Norja A, Auriola S, Mauriala T, Mäki M, Kaukinen K.
Degradation of coeliac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic effects in intestinal epithelial cells. Clin Exp Immunol 2010;161:242-9.
Sundman L, Saarialho-Kere U, Vendelin J, Lindfors K, Assadi G, Kaukinen K, Westerholm-Ormio M, Savilahti E, Mäki
M, Alenius H, D’Amato M, Pulkkinen V, Kere J, Saavalainen
P.Neuropeptide S receptor 1 expression in the intestine and
skin--putative role in peptide hormone secretion. Neurogastroenterol Motil. 2010;22:79-87.
Zhernakova A, Elbers CC, Ferwerda B, Romanos J, Trynka G,
Dubois PC, de Kovel CG, Franke L, Oosting M, Barisani D,
Bardella MT; Finnish Celiac Disease Study Group, Joosten LA,
Saavalainen P, van Heel DA, Catassi C, Netea MG, Wijmenga
C.
Evolutionary and functional analysis of celiac risk loci reveals
SH2B3 as a protective factor against bacterial infection.Am J
Hum Genet 2010;86:970-7.
Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, Mc-
Annual Report 2010
Koskinen O, Lindfors K, Collin P, Peräaho M, Laurila K, Woolley N, Partanen J, Mäki M, Kaukinen K
Intestinal transglutaminase 2 specific antibody deposits in nonresponsive coeliac disease.
Dig Liver Dis 2010 ;42(10)692-7
Kaukinen K, Collin P, Mäki M
[Celiac disease--a diagnostic and therapeutic challenge].
Duodecim 2010 ;126(3)245-54
Kurppa K, Ashorn M, Iltanen S, Koskinen LL, Saavalainen P,
Koskinen O, Mäki M, Kaukinen K
Celiac disease without villous atrophy in children: a prospective
study.
J Pediatr 2010 ;157(3)373-80, 380.e1
Dubois PC, Trynka G, Franke L, Hunt KA, Romanos J, Curtotti
A, Zhernakova A, Heap GA, Adány R, Aromaa A, Bardella MT,
van den Berg LH, Bockett NA, de la Concha EG, Dema B, Fehrmann RS, Fernández-Arquero M, Fiatal S, Grandone E, Green
PM, Groen HJ, Gwilliam R, Houwen RH, Hunt SE, Kaukinen
K, Kelleher D, Korponay-Szabo I, Kurppa K, MacMathuna P,
Mäki M, Mazzilli MC, McCann OT, Mearin ML, Mein CA,
Mirza MM, Mistry V, Mora B, Morley KI, Mulder CJ, Murray
JA, Núñez C, Oosterom E, Ophoff RA, Polanco I, Peltonen L,
Platteel M, Rybak A, Salomaa V, Schweizer JJ, Sperandeo MP,
Tack GJ, Turner G, Veldink JH, Verbeek WH, Weersma RK,
Wolters VM, Urcelay E, Cukrowska B, Greco L, Neuhausen SL,
McManus R, Barisani D, Deloukas P, Barrett JC, Saavalainen P,
Wijmenga C, van Heel DA
Multiple common variants for celiac disease influencing immune
gene expression.
Nat Genet 2010 ;42(4)295-302
Caja S, Myrsky E, Korponay-Szabo IR, Nadalutti C, Sulic AM,
Lavric M, Sblattero D, Marzari R, Collighan R, Mongeot A,
Griffin M, Mäki M, Kaukinen K, Lindfors K
Inhibition of transglutaminase 2 enzymatic activity ameliorates
the anti-angiogenic effects of coeliac disease autoantibodies.
Collin P, Mäki M, Kaukinen K
Revival of gliadin antibodies in the diagnostic work-up of celiac
disease.
J Clin Gastroenterol 2010 ;44(3)159-60
Kurppa K, Collin P, Sievänen H, Huhtala H, Mäki M, Kaukinen
K
Gastrointestinal symptoms, quality of life and bone mineral density in mild enteropathic coeliac disease: a prospective clinical
trial.
Dahlbom I, Korponay-Szabó IR, Kovács JB, Szalai Z, Mäki M,
Hansson T
Prediction of clinical and mucosal severity of coeliac disease and
dermatitis herpetiformis by quantification of IgA/IgG serum
antibodies to tissue transglutaminase.
J Pediatr Gastroenterol Nutr 2010 ;50(2)140-6
Koskinen O, Collin P, Lindfors K, Laurila K, Mäki M, Kaukinen
K
Usefulness of small-bowel mucosal transglutaminase-2 specific
autoantibody deposits in the diagnosis and follow-up of celiac
disease.
J Clin Gastroenterol 2010 ;44(7)483-8
Tissue Biology
Hallerdei J, Scheibe RJ, Parkkila S, Waheed A, Sly WS, Gros G,
Wetzel P, Endeward V
T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in
skeletal muscle.
PLoS One 2010 ;5(12)e15137
Pan PW, Käyrä K, Leinonen J, Nissinen M, Parkkila S, Rajaniemi H
Gene expression profiling in the submandibular gland, stomach,
and duodenum of CAVI-deficient mice.
Transgenic Res 2010 ;
Pan PW, Waheed A, Sly WS, Parkkila S
Carbonic anhydrases in the mouse harderian gland.
J Mol Histol 2010 ;41(6)411-7
Aspatwar A, Tolvanen ME, Ortutay C, Parkkila S
Carbonic anhydrase related protein VIII and its role in neurodegeneration and cancer.
Curr Pharm Des 2010 ;16(29)3264-76
47
Di Fiore A, Truppo E, Supuran CT, Alterio V, Dathan N, Bootorabi F, Parkkila S, Monti SM, De Simone G
Crystal structure of the C183S/C217S mutant of human CA VII
in complex with acetazolamide.
Bioorg Med Chem Lett 2010 ;20(17)5023-6
Syrjänen L, Tolvanen M, Hilvo M, Olatubosun A, Innocenti A,
Scozzafava A, Leppiniemi J, Niederhauser B, Hytönen VP, Gorr
TA, Parkkila S, Supuran CT
Characterization of the first beta-class carbonic anhydrase from
an arthropod (Drosophila melanogaster) and phylogenetic analysis of beta-class carbonic anhydrases in invertebrates.
BMC Biochem 2010 ;1128
Saari S, Hilvo M, Pan P, Gros G, Hanke N, Waheed A, Sly WS,
Parkkila S
The most recently discovered carbonic anhydrase, CA XV, is expressed in the thick ascending limb of Henle and in the collecting ducts of mouse kidney.
PLoS One 2010 ;5(3)e9624
Baranauskiene. L, Hilvo M, Matuliene. J, Golovenko D, Manakova E, Dudutiene. V, Michailoviene. V, Torresan J, Jachno J,
Parkkila S, Maresca A, Supuran CT, Gražulis S, Matulis D
Inhibition and binding studies of carbonic anhydrase isozymes
I, II and IX with benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulphonamides.
J Enzyme Inhib Med Chem 2010 ;25(6)863-70
Kallio H, Hilvo M, Rodriguez A, Lappalainen EH, Lappalainen
AM, Parkkila S
Global transcriptional response to carbonic anhydrase IX defi- Parkkila S, Lasota J, Fletcher JA, Ou WB, Kivelä AJ, Nuorva K,
ciency in the mouse stomach.
Parkkila AK, Ollikainen J, Sly WS, Waheed A, Pastorekova S,
BMC Genomics 2010 ;11397
Pastorek J, Isola J, Miettinen M
Carbonic anhydrase II. A novel biomarker for gastrointestinal
stromal tumors.
Oksala N, Levula M, Pelto-Huikko M, Kytömäki L, Soini JT, Mod Pathol 2010 ;23(5)743-50
Salenius J, Kähönen M, Karhunen PJ, Laaksonen R, Parkkila S,
Lehtimäki T
Carbonic anhydrases II and XII are up-regulated in osteoclast- Agborsangaya C, Toriola AT, Grankvist K, Surcel HM, Holl K,
like cells in advanced human atherosclerotic plaques-Tampere Parkkila S, Tuohimaa P, Lukanova A, Lehtinen M
Vascular Study.
The effects of storage time and sampling season on the stability
Ann Med 2010 ;42(5)360-70
of serum 25-hydroxy vitamin D and androstenedione.
Nutr Cancer 2010 ;62(1)51-7
Bootorabi F, Jänis J, Smith E, Waheed A, Kukkurainen S,
Hytönen V, Valjakka J, Supuran CT, Vullo D, Sly WS, Parkkila S
Analysis of a shortened form of human carbonic anhydrase VII
expressed in vitro compared to the full-length enzyme.
Biochimie 2010 ;92(8)1072-80
Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran
CT
The coumarin-binding site in carbonic anhydrase accommodates
structurally diverse inhibitors: the antiepileptic lacosamide as an
example and lead molecule for novel classes of carbonic anhydrase inhibitors.
Nordfors K, Haapasalo J, Korja M, Niemelä A, Laine J, Parkkila J Med Chem 2010 ;53(2)850-4
AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila S,
Haapasalo H
The tumour-associated carbonic anhydrases CA II, CA IX and Agborsangaya CB, Surcel HM, Toriola AT, Pukkala E, Parkkila
CA XII in a group of medulloblastomas and supratentorial prim- S, Tuohimaa P, Lukanova A, Lehtinen M
itive neuroectodermal tumours: an association of CA IX with Serum 25-hydroxyvitamin D at pregnancy and risk of breast
poor prognosis.
cancer in a prospective study.
Eur J Cancer 2010 ;46(3)467-70
Tampere Graduate Program of
Biomedicine and Biotechnology
TGPBB is a joint graduate program with
participants from the Institute of Biomedical
Technology and the Medical School, University
of Tampere and the Departments of Signal
Processing, Biomedical Engineering, and
Automation Science, Tampere University of
Technology.
TGPBB focuses on multidisciplinary research
training in molecular biology, biomedicine,
biotechnology, bioinformatics, cell biology and
systems biology.
Currently, there are 45 research groups enrolled in
TGPBB and approximately 80 registered students
are working towards a doctoral degree in TGPBB
affiliated laboratories.
TGPBB has 20 graduate student positions funded
by the Ministry of Education and Culture to
support full-time graduate research.
In 2010, 13 students completed their doctorates,
and in 2008-2010 altogether 41 TGPBB students
received their doctoral degrees.
http://www.uta.fi/ibt/tgpbb/
Aspatwar A, Tolvanen ME, Parkkila S
Phylogeny and expression of carbonic anhydrase-related proteins.
BMC Mol Biol 2010 ;1125
Järvelä S, Rantala I, Rodriguez A, Kallio H, Parkkila S, Kinnula
VL, Soini Y, Haapasalo H
Specific expression profile and prognostic significance of peroxiredoxins in grade II-IV astrocytic brain tumors.
48
Annual Report 2010
INSTITUTE OF BIOMEDICAL TECHNOLOGY
49
Multidisciplinary expertise in
Multidisciplinary expertise in
life science
science
life
Tampere University of Technology (TUT) and University of
Tampere (UTA) have a long tradition of high-level research
and education related to life sciences and medical technology.
Over 250 scientists in various departments have for many
years conducted research and education in the fields of cell
and molecular biology, genetics, biomaterials, biosensors,
computational systems, biotechnology, biomedical engineering,
and regenerative medicine. At the beginning of 2011 the two
Universities agreed to start the integration of these activities
and establish a combined organization, BioMediTech.
BioMediTech, a joint institute of TUT and UTA, brings together a
powerful mix of multidisciplinary expertise in life sciences and
medical technology. The institute aims not only to integrate
and strengthen the local tradition of excellence in basic
Excellence in
research
BioMediTech conducts world-class basic and
translational research in biomedicine and medical
technology. Its research activities cover diverse
fields, including biomaterials, stem cells, cancer,
immunology, biosensors, imaging, and computational
methods, with a common aim of developing
personalized medicine via new diagnostic and
treatment methods. The institute also houses FinMIT,
the Academy of Finland Centre of Excellence in
research on mitochondrial disease and ageing.
and, consequently, to produce stem-cell transplants
for clinical use. Our adult stem-cell research group
pioneered the generation of cranial bone derived from
patients’ own fat tissue in 2007. Since then, more
than 20 patients have successfully received cranial
and facial bone transplants created in this fashion.
During the last ten years the research groups
of BioMediTech have produced close to 1500
publications in international peer-reviewed journals,
nearly 100 patents and over 10 commercial spin-offs.
BioMediTech provides state-of-the-art laboratory
and clean-room facilities, and implements relevant
quality systems. These have enabled us, for
The institute is funded by national and international
agencies such as the Finnish Funding Agency for
Technology and Innovation (TEKES), Academy of
example, to be among the first units in the world
to initiate stem cell production in compliance with
pharmaceutical manufacturing requirements (GMP)
Finland, the Council of Tampere Region, the European
Union and its frontier-sciences arm, the European
Research Council.
Promoting
Unique
BioMediTech aims to nurture innovation and
commercialization of research results via an active
patenting policy, by providing expert advice to
its scientists on the innovation potential of their
discoveries, and by fostering spin-offs. Research
environment
life-science research and teaching, but also to create new
platforms for discovery and innovation.
innovation
50
Annual Report 2010
educational
BioMediTech is also pioneering a unique educational
environment by combining UTA-based biosciences
and TUT-based technology into a single degree
programme, which is planned to start in the autumn
groups participating in BioMediTech have a long
history of exploitation of research findings. For
example, the Biomedical Engineering unit and its
of 2012. The main objective of the new degree
programme will be to educate top-level experts
with multidisciplinary skills in life sciences for the
predecessors at TUT were the first in the world to
develop bio-absorbable implants such as screws and
plates for bone fixation.
demands of both academia and industry.
51
Annual Report 2010
To the Reader:
At the beginning of 2011, Regea Institute for Regenerative Medicine and the Institute of
Medical Technology were merged to form the Institute of Biomedical Technology (IBT).
http://www.uta.fi./ibt/
The new Institute cooperates closely with related departments at Tampere University of
Technology (TUT). The aim is to create an interdisciplinary, internationally high standard
research and education institute - BioMediTech.
BioMediTech, begun its work on August 31, 2011, as a joint institute of Tampere University
of Technology and University of Tampere, bringing together a powerful mix of multidisciplinary expertise in life sciences and medical technology. Over 250 scientists conduct research
and education in the fields of cell and molecular biology, genetics, biomaterials, biosensors,
computational systems, biotechnology, biomedical engineering, and regenerative medicine.
The Institute aims not only to integrate and strengthen the local tradition of excellence in
basic life-science research and teaching, but also to create new platforms for discovery and
innovation.
http://www.biomeditech.fi/
52
Annual Report 2010

IMT Annual Report 2010

Transcription

Similar documents

international conference places on the edge creating a sense of

Distortion Social

You Can Help - Goombay Bash

Interconnected World

The International PhD program in Biomedicine and

Antenne planari altamente direttive per investigazioni in spazio

What is the Electron Transport Chain?

Automaalit

In the m iddle of July the Autoglym Rally is run on - PR

Timo Vuorensola, allies and Iron Sky revolutionize

8823278-LuovaTampere_Today

BioMediTech Research Day 2013 Abstract Book