PDF - ScienceRelations
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PDF - ScienceRelations
Annual Report 2010/2011 Luxembourg Centre for Systems Biomedicine »Building up« Editorial Professor Dr. Rudi Balling, Director LCSB of disease stratification from this, however, not neglecting to look also at genomics, proteomics and transcriptomics, which we do with our partners in the US, especially the Institute for Systems Biology (ISB) in Seattle, our most important knowledge transfer partner. They have done a great job in supporting us, complementing us, and even promoting us in our development to what we are now. International and interdisciplinary cooperation, building partnerships with the best in the world is the key to being successful in the rapidly changing landscape of biotechnology and Information and Communication Technology. Building things up has always been my passion. This is why I could not resist accepting the offer to become the first director of LCSB and gain the chance to once again start from scratch – literally I can say. The beautiful building into which we have moved just now in August 2011 did not exist in those first days. It is one of the examples what a small but powerful country like Luxembourg can do. I have never seen buildings made functional in such a short time. »We can do it« seems a motto of this country and I would like to adopt it for LCSB as well. And we do meet the challenge. From one employee – myself in September 2009 – we have built seven research groups, led by young people full of ideas, full of enthusiasm. I am proud of these highly motivated investigators. Together we have already secured more than 3,5 Mio € in external grants. What is ahead of us? Genome wide omics and imaging will provide us with a tsunami of data. LCSB´s challenge will be to turn the available information into knowledge. This will require major efforts in data acquisition, handling, storage and of course data analysis. The future LCSB will be as much a computer centre as it will be a biology centre, both being in line with the priorities of the University of Luxembourg. I feel honoured that I was trusted to take up this important mission of building up systems biology in Luxembourg. But how to fulfil such great expectations? My deep persuasion is: to be successful you need to focus. Focusing has to be done on all levels: as a centre for systems biomedicine by selecting a specific disease area. I chose neurodegenerative diseases, more specifically Parkinson’s Disease, with an attempt to meet the challenges of an ageing population, and to address the concerns of people that they may lose the command of their body and even more scarily of the function of their brain. Neurodegenerative diseases – one of the major challenges for the general population as well as for research. With LCSB we want to contribute one building block for the future of Luxembourg. More have been created with the Integrated BioBank of Luxembourg (IBBL), with the CRP Santé and its Lung Cancer Programme (PPM). Together we form a strong pillar through the Personalised Medicine Consortium. Together we want to put Luxembourg on the map of biomedicine. Systems biomedicine means that you consider the entire system, employing all technologies to get at the cause of disease and health. Again, one research institute cannot do everything, focusing is needed. Aiming at the patient in systems medicine, we chose metabolomics and imaging, technologies to measure and visualise what is going on inside the body. We hope to gain a better understanding Yours. Thanks for all the support and interest. Rudi Balling Director LCSB 1 The LCSB is accelerating biomedical research by closing the link between systems biology and medical research. Collaboration between biologists, medical doctors, computer scientists, physicists and mathematicians is offering new insights in complex systems like cells, organs, and organisms. These insights are essential for understanding principal mechanisms of disease pathogenesis and for developing new tools in diagnostics and therapy. Neurodegenerative diseases like Parkinson’s Disease, metabolomics and disease network analysis are in the focus of LCSB’s research. Within Luxembourg the LCSB is building up strong partnerships with all major biological and medical research units. Key strategic partnership has been set up with the ISB in Seattle. The LCSB fosters collaboration with industrial partners and will be a focal point for developing a knowledge based economy in Luxembourg. Table of Content Our Team Spirit must move with us to Belval! 4 Parkinson’s Disease and the Quest for a Cure 6 All set for Cell Culture 8 From the Lab to the Computer Model 10 Metabolism Detectives at LCSB 12 The Principal Investigators of LCSB 14 Planning, Building, Moving: LCSB in Belval 16 Education at LCSB: PhD Students 18 Cooperations: Research together efficiently 19 ISB in Seattle: Learn from the Best 20 The »Kanneruni« 21 Parkinson Symposium at LCSB 22 Media Coverage 23 Facts & Figures 24 Publications 28 2 3 Spirit of LCSB Our Team Spirit must move with us to Belval! Rudi Balling on the establishment of the LCSB and systems biomedical research for Parkinson’s patients. Professor Dr. Rudi Balling foresees significant progress in the diagnosis of Parkinson´s Disease. family commitments are faced with great challenges. I believe that we should try to understand Parkinson’s on a molecular, cellular and organismic level as a model for neurodegenerative diseases. It would be an important step in finding new diagnostic and treatment techniques - and in the long term, fundamentally improve the condition of patients, doctors, care takers and family members.« Professor Dr. Balling in autumn 2009 you came to Luxembourg to build up the Luxembourg Centre for Systems Biomedicine. What was that like? Balling: »Incredibly exciting. Amazing opportunities awaited me - as well as a blank sheet of paper, namely the possibility to plan a new institute from scratch. When I arrived, I was given an office, a co-worker and a computer. That may not seem like much at first. But the background! The political commitment with Luxembourg aiming at being put on the biomedical research map, the perspective of setting up a new laboratory building within the midst of a new University campus, and the willingness of the external environment to pull together - all that helped me enormously at the start.« A disease as a model? »Yes, we want to understand neurodegenerative diseases of the brain: How does a disease like Parkinson’s flare up? Where are the relays that need to be fixed in order to prevent, undo or at least effectively minimise a flare-up? That is why the institute has »Systems Biomedicine« in its name. You are a nutrition scientist, mouse geneticist, infections researcher. Now you are dealing with Parkinson´s Disease. Why? Of course it will be impossible to understand the disease down to the last detail. And we do not need to. What we need is an ever improving overview over the basic disease mechanisms. That will help us know what to take into consideration when working on better diagnostic and treatment techniques and the details we have to settle. We will leave the more coincidental trial and error in medical research and instead move closer to selectively influencing vital set screws in the system cell-organism-disease.« »The decision to orientate the LCSB toward Parkinson’s Disease has two reasons. For one, there already exists very good clinical research on Parkinson’s Disease here in Luxembourg. For another, medical requirements speak for more intensively dealing with this neurodegenerative disease. Parkinson’s is triggered by a variety of factors: age, genetic disposition and environmental factors play important parts. It’s a highly complex interplay that, from a scientific perspective, is demanding and exciting. Sounds rather reductionist. »You can only effectively change something if you have understood the system in its main features. To some extent, we biologists should see engineers as role models: No new wide-body aircraft, no rocket is ever launched before Naturally, however, the scientific interest isn’t the only driving force: Neurodegenerative diseases will hit more and more people in our aging society. Supply systems and 4 And that’s where bioinformaticians and mathematicians come in: They will analyse the data and, by modelling and simulating, try to discover the important set screws in the system »energy supply of neurons,« which biologists will then take a closer look at experimentally. That way we proceed step by step: Experimental data generates better modelling, modelling data generates better experiments.« the functionality of all systems has been modelled and simulated on a computer - thus before the system has been regarded upon as a whole and works. We have to keep explaining this research approach in terms everyone can understand - otherwise acceptance issues are inevitable. After all, an organism isn’t a plane; it has a completely different moral value. When we say that we analyse it as a system, then that is merely an auxiliary construction of thought to get a rough picture of its tremendous complexity.« How does the patient benefit? »I am confident that we will soon make progress in the diagnosis of Parkinson’s. Thanks to high throughput techniques, we will identify markers - biological substances - that indicate certain pathological processes in the body. That will improve the early diagnosis of Parkinson’s. Another example: There is no typical Parkinson’s patient, but many different specificities and subtypes. Therefore, patients react very differently to medication. What helps one person may be ineffective in another case or, at worst, even damaging. With the help of biomarkers, we can better diagnose which Parkinson’s type is linked to which specific indisposition - and how the patient should be treated best.« How do you intend to proceed, Mr Balling? »First we have to find out why, with Parkinson’s Disease, neurons in the substantia nigra - a part of the midbrain - die off. Why there and not in other parts of the brain? Then we need to study the cause of this. What really happens inside the neurons of the substantia? We have some first clues: Something isn’t right with the energy supply in the neurons; the mitochondria, namely the power plants of the cells, aren’t fully functional and cannot provide sufficient energy. We want to understand the system of energy supply in neurons; we want to find out which system-related parts are out of order and what kind of effects this has on other components of the cell. Where do you see the future? » I believe that we have already achieved what’s most important: We have recruited great researchers who can think creatively. From the secretarial office to the infrastructure, the PhD students to the senior scientist, at LCSB imagination, excitement and optimistic spirit prevail. The close proximity of scientists that cover many disciplines from mathmatics to the clinic will then catalyse a huge load of exciting new ideas!« For this, we use classic biological laboratory techniques. Our cooperation partners, for example medical labs in Luxembourg, provide us with samples that we analyse using gas chromatography, mass spectrometry, microscopy - and, in contrast to the past, we can now collect significantly more data. We call it high throughput: in our new laboratories in Belval, robots will take care of pipetting or microscopy. It’s the only way we can collect sufficient amounts of data for the systems medical approach. 5 Background Parkinson’s Disease and the Quest for a Cure LCSB´s science is focused on Parkinson´s Disease. But what are the implications of this illness with which Nico Diederich is confronted in his daily work at the Centre Hospitalier de Luxembourg and at the LCSB. An overview. »When I was trying to put my coins in your coin machine, I dumped $83.52 of coins on your floor. I sometimes can be very shaky,« blogged Kate Kelsall in September 2006, telling a story of her everyday life. It is a »thank you note (...)« to her bank, honoring one of the employees for helping while acting »like it was a normal occurrence« – even though both knew it was not. The today 61-year-old is one of about five million Parkinson (PD) patients worldwide. This makes Parkinson’s the second most common neurological disease of the elderly. But even though Deep Brain Stimulation, medications and speech therapies make the illness manageable – the hunt for better diagnosis and a cure continues. Described first by James Parkinson in 1817, a huge step in the groundwork for Parkinson´s was made when the Swedish physiologist Arvid Carlsson got to the bottom of the illness in the 1950’s: death by unknown causes of dopamine-containing cells in the substantia nigra within the basal ganglia of the brain. Research progressed steadily since then but still the disease affects one in 100 people over the age of 60. Kelsall herself was diagnosed at age 46. Ten years later, the former director of finance was considered to be in an advanced stage. »I am grateful that I seldom fall and have never frozen. But I also realize that falling and freezing could just be around the corner, and I need to be prepared for this eventuality.« she wrote at the beginning of her blog. other abnormalities include autonomic dysfunction, sensory difficulties or neuropsychiatric problems. »X-Xenophobia, Y-Yin, yang, yoga, Z-Zombie« – with these words Kelsall ends her symptom-ABC, after listening to a presentation of a new doctor in town. »I counted 96 symptoms and side effects that he spewed out in 75 minutes«. cording to a study of the National Parkinson’s Foundation in April, that is why people do not go to the doctor, even though serious symptoms appear. It is an outraging situation. Therefore scientists like those at the LCSB search for example, for reliable biomarkers. They are not only supposed to help treating the disease but also to diagnose PD early. In that case a medical device, a brain pacemaker, is implanted. It sends electrical impulses to specific parts of the brain, blocking the abnormal nerve signals that cause PD symptoms. However it is not fully understood how DBS works. For Kate Kelsall »DBS is not a black and white issue, but one that includes many shades of gray.« Some symptoms occur early before the first diagnosis, such as a reduced ability to smell. For Dr. Nico Diederich, head of the neurology department at the Centre Hospitalier de Luxembourg and Clinical Senior Researcher at the LCSB, one of the most interesting symptoms described in the last years has been a disturbance in the REM sleep, called Rapid Eye Movement Sleep Behaviour Disorder (RBD). About two thirds of the patients are diagnosed with parkinsonism about 20 years later. Not knowing the cause of the specific cell death in the brain complicates the situation, too. What is certain is that the more cells that perish, the more difficult the therapy becomes. As fast as she could, Kelsall tried everything in her »quest for a PD cure«. She took medications – »sometimes as many as 13 pills a day« –, vitamins, got massaged and more. But even though »some of these measures provided temporary relief, it was more like putting a Band-Aid on a gun shot wound.« It has been 15 years now since Kelsall learned that she has Parkinson’s. She still suffers from it, but she tries to not allow the illness to interfere with her life. She dances, plays the accordion – and dedicates her blog »to spreading awareness of the realities behind having it«. Meanwhile Diederich and his colleagues try to improve the diagnosis, develop therapy methods and work on new research approaches such as gene therapy and the role of mitochondria. They are two quests linked by one thing: the hope to someday find the cause of Parkinson’s. Kate Kelsalls medical history began with a shaking left hand, a weak arm, dropping things and a soft and raspy voice. Left with the question, what is wrong? After two months of neurological testing Kelsall got her result: »I have good news and bad news (...) The good news is that you don not have a brain tumour, Lou Gehrig’s disease or Wilson’s disease. The bad news is that it appears that you have Parkinson’s Disease.« It was not the answer that she wanted to hear. At the same time it can not be denied that today’s treatments buy patients some time. »We can not heal it, but thanks to medication we have a handle on it,« says Luxembourg’s researcher Diederich, talking about motor symptoms. The development of the most used medicine was based on Carlsson’s research: L-Dopa is an orally administered medication, given either in a regular or a delayedacting form, which has a longer lasting effect. Inside the brain, at the nerves, the prodrug is converted to dopamine, replacing some of the missing chemical. Still she was »lucky« that she was diagnosed and received treatment so quickly »unlike others who go for years and years, from doctor to doctor, without an accurate diagnosis and receive either no or inappropriate treatment.« Diagnosing the illness is quite difficult. A direct test does not exist and some metabolic disorders as well as other factors can mask PD. This leads to a high error rate. Ac- The symptoms of the illness are multifaceted: resting tremor, balance problems, muscle rigidity and a flat facial affect are all early signs. Next to these motor-symptoms 6 The problem: Levodopa’s response, as well as other medication, declines within years and sometimes stops completely. »Some Patients that do not respond to pharmacologic therapies anymore or suffer from extreme side effects could be treated with Deep Brain Stimulation (DBS),« says Diederich. LCSB scientists investigate mitochondrial dysfunctions in dopaminergic neurons. They might be one cause of Parkinson´s Disease. 7 Cell Biology All set for Cell Culture Sandra Koeglsberger - the technical assistant makes Balling´s lab run. To better understand Parkinson’s Disease, Rudi Balling´s team is planning experiments with brain cells – and at the same time, it is setting up a fully automated laboratory for cell-biological experiments now, says Antony, to analyse cells at the LCSB that play a key role in Parkinson’s: the dopamine-producing cells of the substantia nigra, a specific region in the brain. These die off in Parkinson’s patients and thus release the symptoms of the disease. »There were only lab benches here, other than that, the room was empty,« says Dr. Paul Antony , member of Rudi Balling´s experimental biology research team. The room that is the central laboratory of the LCSB in early summer 2011. And it was empty a year before. »However, I had a computer from day one,« Antony recalls his beginnings at LCSB, »and that’s, what was most important!« What else does a scientist need, apart from his laptop, clean bench, incubator, centrifuge and specialised equipment, for a fully automated cell culture lab? To design a research plan for years to come and all the while not lose sight of the specific experiments? To hire competent co-workers and instruct doctoral candidates who do not yet have a lab place, but need to make progress so that their three doctorate years do not slip through their fingers? Paul Antony does not speak about what it is you need for all this, apart from the computer. But when you talk to him, you notice: So what happens exactly? What are the reasons for the cells‘ death? And what can we do against it? These are the three central questions to which Paul Antony and the other LCSB scientists want to know the answers. Antony sort of stands at the beginning of the research chain. Because he studies them directly, the dopaminergic cells. For that he needs a modern cell culture laboratory. To research the many variables in gene mutations and environmental influences that lead to Parkinson’s, one has to run so many tests that the experiments need to practically work automatically. The scientists want to see exactly what happens in the cells before they die. They need specialised microscopes that can photograph cell cultures - also automatically. Large data volumes are produced and a lot of effort is put into being able to save everything correctly and automatically in a computer, to keep it retrievable and to evaluate it. One needs a clear objective, the skill to inspire people and get them excited about a good cause, as well as experience in scientific work. Luxembourg-born Antony accumulated these skills during his studies in Strasbourg and his doctorate in Tübingen, Germany. Brain cells were also his subject of study then; though at the time it was not for Parkinson’s, like now at the LCSB. Antony first examined the Machado-Joseph disease (MJD), a hereditary neurodegenerative disease, in which - similarly to Parkinson’s - cells in certain regions of the brain die off. At both stations, in Strasbourg as in Tübingen, Antony was able to acquire important tools for his research at LCSB: »In France, I took more math classes than I could have in Germany. In Tübingen we studied mostly genetics and molecular biology.« He needs all this As already mentioned: In summer 2010 the laboratory was almost empty. »By autumn 2011, we’ll be all set,« says Antony. He has mastered a Herculean task in the past twelve months. »Of course I couldn´t do it alone,« he admits humbly. His - few - co-workers have equally high skills in their fields of specialty as he does. For one, there is Aidos Baumuratov, specialist for microscopy. A computer was also all he had when he started off. »He needed it to screen the market for special microscopes,« says Antony, »He picked the best one for our needs and ordered extra 8 equipment so that we could later observe the neurons without causing them stress during experiments and thus get erroneous results.« Other members of the team are technical assistant Sandra Koeglsberger, who is mainly responsible for the cell cultures thriving and thus enabling precise results, and Christophe Trefois. He is in fact a doctoral candidate under the supervision of LCSB director Rudi Balling. In the lab, Trefois works for and with Paul Antony. »We both benefit,« Antony confirms. Christophe Trefois is a trained engineer. He first found interest in biology during his doctoral work. In the laboratory, he learns about cell culture technology and in return he shares his knowledge of engineering: »I know how robots function and how to programme them,« says Trefois. So he uses his computer to search for the right cultivation robot and orders testing devices that he then thoroughly examines in the lab. For the LCSB the goal is to build up a perfect cell culture lab in autumn 2011 and to investigate the causes of Parkinson’s with neurons under optimal conditions. Dr. Paul Antony - PostDoc in the Experimental Biology Group at LCSB and PhD student Christophe Trefois are testing a cultivation robot. 9 Bioinformatics and Computational Biology From the Lab to the Computer Model Reinhard Schneider´s Bioinformatics Core Unit and Antonio del Sol´s Computational Biology make sure that laboratory data lead to systems biological findings. These are supposed to enable progress in diagnosis and treatment of Parkinson’s Disease. Dr. Reinhard Schneider leads the Bioinformatics Core Unit at the LCSB. He is familiar with the difficulty of this rather abstract field of expertise: »Imagine planning a big celebration for a milestone birthday. Your preparation work will resemble that of a bioinformation scientist.« How come? »You channel wide-ranging data through a process using different computer programmes and work tools, and at the end you hope a wonderful party will come out,« Schneider explains: »First you make out a list of names using your directory, then you look for any missing contact information by doing a search on the internet. With your computer’s word processor you write the invitation, while an image editing programme makes that old picture from your childhood look more flattering.« This continues up to when you set up a list of digital songs for the DJ and pick out the food on the caterer’s web site, the bioinformatician enumerates, »we do the same with the data from our biology labs, we run them through different computer tools and prepare them for the network analysis. We design those tools ourselves and perform research in this field. Our own party is unravelling a piece of the mystery in a cell, life form or disease.« bioinformaticians work with. Computational biologists develop mathematical and computational tools based on experimental data in order to understand biological processes. The head of the department is Ass. Prof. Dr. Antonio del Sol: »Our aim is to understand molecular networks that control the biological processes,« says the scientist. This, he says, is the key to a deeper understanding of diseases like Parkinson’s. »Parkinson’s is triggered by perturbations, failures, in the equilibrium of the molecular network,« del Sol continues. Such failures could be gene mutations, protein malfunctioning, reaction to toxins or completely unknown factors. »Because there is an unbelievably big amount of factors that can lead to failure, we have to feed as much data from different sources into our network analysis as possible,« del Sol is convinced. One of these sources, for whom the central bioinformatics unit prepares the data, are of course the LCSB laboratories. »However, we also look for this information outside of the LCSB,« says del Sol. For example in publicly accessible data banks, which list information on genes, proteins and metabolism. »We also cooperate with other laboratories that provide us with data records for our network analysis.« Schneider‘s group connects two fields of biological research - on one side the laboratory and on the other the theoretically oriented research in computational biology. Schneider: »We help the experimental scientists treat and analyse the data from the experiments.« Apart from the hardware, his team therefore provides the correct software, and adapts or rewrites these - specifically tailored to the needs of the scientists in the lab. To make communication easy, Schneider hires bioinformaticians with a broad scientific background in biology and biochemistry, mathematics and physics, all the way to medicine. »What they all have in common is a sense for computer science and handling large data volumes,« says Schneider, »In addition, it is important that they listen carefully to researchers in other disciplines - that is the only way to build a bridge between biology, bioinformatics and computational biology.« Why then, does computational biology need to be part of an institute like the LCSB in the first place? External data is not enough to do systems analyses on a high scientific level, Antonio del Sol believes: »It is very difficult to standardise and control the quality of data that is produced in other labs: The contact to other scientists is never as close as that between those from our own institute.« And exchange between scientific fields is most important when aiming to be successful using computational biology in diagnosis and treatment: »Our analyses, models and simulations of disease processes yield clues on where there might be relays in the network that could be interesting for diagnosis or treatment. To turn these assumptions into verifiable knowledge, we have to keep refining the experiments in the lab that provided the data until we get a validated picture of the entire network.« Such a close and critical exchange on subtleties of experiments is only possible, according to del Sol, if there is daily contact between colleagues in their own organisation. Dr. Reinhard Schneider leads the Bioinformatics Core Unit at the LCSB. Ass. Prof. Dr. Antonio del Sol is head of the LCSB Computational Biology Group Computational biology is the other side of research that 10 Network analysis explains how diseases suddenly break out Computational biology analyses molecular networks to better understand disease mechanisms. At the LCSB, this will yield new findings on Parkinson’s Disease in future. Often, numerous environmental factors or genes are involved when people fall ill. »We have found pointers that with certain diseases, a group of genes will form a sort of core network within the complete network,« says del Sol. The state of this core network - namely the intensity with which the group of genes is read and their coded information is transcribed in proteins - is part of a »disease sequential circuit«. The whole sixth floor of new LCSB building is equipped with high performance computer servers The circuit can point in the directions »healthy« or »ill«. Certain factors - for example the structure of individual, especially important proteins - determine whether and when the circuit changes from »healthy« to »ill« and thus greatly shifts the fragile molecular balance. This leads to more negative changes in further located parts of the molecular network: The disease breaks out. 11 Metabolomics Metabolism Detectives at LCSB Karsten Hiller is setting up the LCSB work group »Metabolomics«. With state-of-the-art techniques, he and the scientists of his team aim to understand how and why the metabolism of brain cells in Parkinson’s patients runs out of control. Scientists travel to all corners of the earth: conventions, lectures, their postdoctoral training or research stays take them to foreign countries and to new continents. This leads to new collaborations and sometimes to a switch to a new lab. Only rarely, however, do two researchers first live in one and the same city without their paths ever crossing, then coincidentally meet on a different continent attending the same lecture, and finally they jointly work on setting up a new institute. This is exactly what happened with Dr. Karsten Hiller and Prof. Dr. Rudi Balling. many labs: »I had the feeling that we could fill a gap with metabolomics and that with the right people, we could be leading at the top,« says Balling, »the right person is Karsten Hiller, because he perfectly combines laboratory work and bioinformatics.« And because he has designed a new dramatically improved technique for analysing metabolic pathways in living beings: A combination of mass spectrometry and stable isotopes to determine the fate of certain components in a cell and uncover previously unknown metabolic pathways (s. box on right page). »In spring 2009 we met for the first time in Boston during a lecture on systems biology,« Karsten Hiller remembers. After earning a PhD degree at the University of Braunschweig in Germany, he spent his postdoctoral years at the Massachusetts Institute of Technology, the famous MIT. »I went to MIT to improve my knowledge of the cellular metabolism in relation to diseases,« says Hiller, who studied biology and computer science with a focus on bioinformatics, »For my dissertation, I examined the characteristics of the metabolism using metabolome analyses.« To analyse experimental mass spectrometric measurements, he designed new algorithms - exclusively using the computer. »Of course you also need laboratory data,« says Karsten Hiller, »That is why the MIT was the ideal place for me, because here theory and practice are closely linked.« Mouse geneticist and infection researcher Balling shared this opinion. In the course of a sabbatical, he had come from Braunschweig to the Broad Institute in Boston, to enhance his theoretical understanding of biology and study mathematics and systems biology. »Chemical elements can be found in nature in variations, which the chemist calls isotopes,« Karsten Hiller explains, »The atomic nuclei of different isotopes of an element differ in composition and mass.« For instance, besides the more abundant carbon atom with twelve nucleons, there are also carbon atoms with 13 or 14 nucleons. The difference in mass is due the different number of neutrons in the nucleus. To study the metabolism, Karsten Hiller uses only stable isotopes of an element, namely those that do not fall apart. With carbon, these are the isotopes with an atomic mass of 12 and 13. »When we feed a cell culture with sugar, in which the common carbon-12 is replaced by carbon-13, the cells integrate these completely harmless isotopes into their metabolism. After a while we can detect them in very different metabolites using mass spectrometry.« The mass spectrometry with stable isotopes has advantages compared to conventional methods: The scientists can observe how the carbon atoms in the labelled sugar spread throughout the components of the cell over time, where metabolic pathways split, cross or come together again. Hiller: »We can rapidly penetrate the deepest ramifications of the metabolism - and thus deliver data that we need at LCSB for the systems biological observation of cells or diseases.« The two of them quickly started talking. For Balling it had become clear that he would set up the LCSB in Luxembourg after his sabbatical. »A focus at the new centre was going to be metabolomics,« he says. Also the other »omics« like genomics and proteomics, he says, are extremely important but have already been well established in 12 Dr. Karsten Hiller: Head of the Metabolomics ATTRACT Research Group. How molecules are identified To prepare samples for mass spectrometry, they first have to be separated - for example the content of brain cells - using gas chromatography. For this, the cell content is made gaseous. Then electrons of the individual molecules in the gas are forced out. That way positively charged ions form, which can be accelerated using electrical fields. With a specific method in mass spectrometry, the scientists measure how fast ionised molecules in a defined electrical field cover a certain distance: The range of their flight depends on the mass of the ion. Thekla Cordes is checking the mass spectrometer. For this, Karsten Hiller closely cooperates with LCSB scientists like Alessandro Michelucci, who is a molecular and cellular biologist. Michelucci came to the LCSB at the beginning of March 2011 and immediately proposed an experiment that would allow Hiller’s mass spectrometry with stable isotopes to exploit its strengths. »In the brain there are a variety of cells for different tasks like information processing or immune defence,« says Michelucci, »If we want to understand why certain neurons die off with Parkinson’s, we have to study how the cell types interact and individually react to specific impacts.« He therefore treated specific immune cells of the brain – so called microglial cells –with a substance that is found on the surface of bacteria and can therefore mimics an infection: a lipopolisaccharide. Then, Karsten Hiller and his team analysed the metabolites made by these cells during an infection. Karsten Hiller‘s combination of mass spectrometry and stable isotopes has the advantage that hitherto unknown metabolic pathways can be studied. »We can detect substances that have been completely unknown up until now or that have not yet been found in a certain metabolic pathway,« says Hiller. This is for example the case for an antibiotic substance that specific brain cells produce after contact with a bacterial signaling molecule, as Hiller’s mass spectrometric studies have revealed: Before, this substance had only been verified in fungi. »No one ever suspected that microglial cells could produce this substance,« says Karsten Hiller. To come to this result, Hiller first had to combine mass spectrometry with stable isotopes. »One substance showed up in a strikingly high concentration,« Hiller describes the result, »At first, we didn’t know what we were dealing with.« Literature and data base analyses, however, were of further assistance. They were dealing with a substance that disturbs the metabolism of bacteria - a sort of endogenous antibiotic. »If this indication should prove itself to be correct in the next months, that would be a great finding,« Hiller says, »because we still know practically nothing about the immune defence in the brain and its impact on the development of Parkinson’s.« 13 The Principal Investigators of LCSB Prof. Dr. Rudi Balling Experimental Neurobiology Group Ass. Prof. Dr. Antonio del Sol Computational Biology Group Dr. Jochen Schneider Translational & Experimental Medicine Group Dr. Karsten Hiller Metabolomics ATTRACT Research Group Dr. Nikos Vlassis Machine Learning Group Dr. Reinhard Schneider Bioinformatics Core Unit Dr. Paul Wilmes Ecosystems Biology ATTRACT Research Group A key goal of Rudi Balling´s group is the analysis of neurodegenerative diseases with an emphasis on Parkinson’s Disease. The goal is to dissect the mechanisms of genetic susceptibility and resistance of this neurodegenerative disease at the individual level and thereby develop the foundations for future approaches in personalised medicine. This involves studies on PD-patients, animal models of PD and cell culture studies of dopaminergic neurons, the cell type most severely affected in PD-patients. Systematic perturbation, high throughput and high content imaging studies are employed to study the role of mitochondrial, proteasome and immune system dysfunction in the pathogenesis of PD. Bioinformatics and systems biology approaches are used to reconstruct regulatory and metabolic disease networks and to identify new targets for the development of specific preventive and therapeutic strategies of PD. Antonio del Sol´s group is involved in modelling and simulating biological processes using different mathematical and computational tools. In particular, Del Sol’s team follows the analysis of biological networks to understand the mechanism of various diseases and predict potential diagnosis and therapeutical targets. His team – with an academic background in biology, computer science, mathematics and physics - is interested not only in the development of theoretical tools for biomedical studies, but also in the application of these tools to concrete diseases. Jochen Schneider is, on the one hand, providing medical care to patients suffering from metabolic diseases or hormonal problems. On the other hand, he conducts basic translational research involving cellular and animal models of diseases as well as clinical research. He concentrates on analysing physiology und pathophysiology of genetic modified model organisms. Schneider´s group is involved in the evaluation of the relevance of systems biomedicine projects in matters of human (patho) physiology and contributes clinical expertise to other groups to link basic science with the needs of modern clinical medicine. He also serves as an interface for the networking with partners and collaborating universities and hospitals. Therefore, his group accompanies medical translational developments from the explorative phase, via the proof of concept, to clinical trials. Karsten Hiller´s Group intends to establish state of the art mass-spectrometric methodologies for the analysis of cellular metabolism. These technologies are applied for shedding light on cellular metabolism. To detect disease related metabolic pathways and to measure intracellular flux changes, the group applies stable-isotope labelled compounds. The researchers are especially interested in cancer and Parkinson‘s Disease. Since both diseases have mitochondrial dysfunction in common, they will setup a platform for the analysis of mitochondrial metabolism. The group addresses research problems in systems biology via the tools of machine learning, which allows dealing with largescale, structured, noisy and high-dimensional data that are often encountered in biology. A mix of Bayesian statistics, stochastic control, graph theory, and optimisation is used for building and analysing models that can explain biological phenomena. The main interest of the group is on the development of new theory and algorithms, but also with a focus on practical problems. Current projects involve: Learning the structure of biological regulatory networks that are responsible for cell plasticity and differentiation via dynamical systems concepts like attracting states and limit cycles, Bayesian modelling and prediction of transcription factor binding sites and the detection of regulatory nucleotide polymorphisms and analysing the circuit space of graphs and hypergraphs for flux analysis in metabolic networks. The group is responsible for the efficient data flow between the experimental groups and the theoretical and medical oriented groups. Schneider’s team deploys and develops techniques and programmes for the data analysis pipeline. His team has a very diverse academic background - from biology and biochemistry, mathematics and physics, all the way to medicine. They have a good sense for computer science and the manipulation of large volumes of data. In addition, they have the ability to conscientiously listen to researchers in other fields - the only way to bridge biology, computer science, and medical science. The main interest of the group is to develop and apply molecular systems biology approaches for obtaining detailed understanding of mixed microbial communities that are of bioenergy and human health interest. The group has developed wet-lab methodologies, which allow truly integrative high-resolution molecular studies of microbial consortia as well as other biological systems. In addition, the group is developing microfluidicsbased bioreactors for conducting multiplex studies of human gastrointestinal microbial assemblages. The overall vision of the group is to use the obtained highresolution molecular data to construct ecosystemwide multiscale models that will allow the steering of microbial communities towards particular end points, e.g. efficient production of bioenergy from wastewater or treatment of microbial communitymediated human diseases. 14 15 LCSB in Belval Planning, Building, Moving In summer 2011, the LCSB moved into its new laboratory building »House of Biomedicine« in Belval, the future location of the University of Luxembourg in Esch-sur-Alzette. The construction had already been planned before the concept for the LCSB was ready. Nevertheless, everything came into place nicely. Thanks to flexible architecture - and a great deal of planning even during construction. These needed to be closely clocked, as states architect Jean-Luc Wagner, a partner in the architectural office WW+: »Shortly before the end of the year 2008, we were given the order to design and implement a laboratory building in Belval. The time frame for finishing was only two years.« In the end, it took nine months longer than that. »At the end of 2008, it was not clear yet who was going to use the building and to which objective,« says Jörg Weber, also a partner at WW+, »That Rudi Balling would establish a lab for systems biomedicine here, only materialised about a year later.« Spring 2011: »Mind the step!« Zino Hemgesberg, LCSB project manager for the new construction in Belval, warns in front of a gap below the landing of the last stair: »This is pretty much the only thing that went wrong in planning and needs to be reworked - and only because the stair company went broke.« Hemgesberg is annoyed about this. But it is the annoyance of a perfectionist. The little gap does not compromise the overall impression of the building: It is bright, friendly, functional, and in a spectacular environment. The laboratory building is located between three huge hot blast stoves, where air used to be preheated for furnaces in the past. Until up to a few years ago, steel production marked the city of Esch. The end of the coal and steel industry resulted in a drastic structural change: The former industrial site turned into a new home for the University of Luxembourg. The LCSB made the first move and relocated to Belval in late summer 2011. Big laboratories, directly connected to offices and computer workplaces, matched the new director’s visions. »We need direct exchange between researchers in the labs and the experts in bioinformatics and computational biology,« says Balling. He believes this is the only way to gain deeper understanding of molecular and genetic networks and develop new diagnosis and treatment techniques against Parkinson’s Disease: »The spatial proximity between the research disciplines is perfectly situated in the new building in Belval,« says Balling. During spring and summer the rush has been intense, trying to get everything ready in time to move. »Almost 70 craftsmen were working here at the same time;« says Hemgesberg. It was therefore necessary to plan the individual steps of the procedure beforehand and in detail. 16 The new »House of Biomedicine« in Belval is located between huge hot blast stoves. 17 Collaborations Building the core of Luxembourg´s Personalised Medicine Consortium: Dr.Guy Berchem (head of Lung Cancer Project PPM at CRP-Santé), Prof. Dr. Rudi Balling (LCSB), and Prof. Dr. Bob Phillips (IBBL). Research together efficiently The Luxembourgish Personalised Medicine Consortium modelling a nation-wide, coordinated network of biomedical research. And carries out joint research projects to the benefit of the patient. Education at LCSB The LCSB PhD students highly profit from an interdisciplinary team as well as from knowledge transfer and exchange with other international institutes: André Wegner investigates the mitochondrial metabolism and how it is related to the death of dopaminergic neurons in the brain of Parkinson’s patients. Isaac Crespo studies how topology and dynamics of biological networks allow us to better understand diseased states and disease progression. Christophe Trefois researches how to detect early warning signs of Parkinson’s Disease - namely clues that point to the outbreak of the disease very early. Aravind Tallam studies how to assess the predictability of mouse models in human diseases: He compares these two organisms at different levels of complexity via computer modelling. Thekla Cordes is sure that everyone can study and compare the metabolism of human cancer cell lines. But to be successful, she also uses stable isotopes. 18 »Not every institute can afford all this,« says Balling: »Targeted cooperations work much better. Especially because of the fact that each specialty lab also needs excellent scientists - and they are even rarer than money.« Medicine faces a revolution. Today, medication is approved and used when it is effective and tolerated by the average patient. The individual person, however, can show distinct deviations from the average on the molecular level. The LCSB and its partners work on changing this situation. Their goal is that in future, diseases can be diagnosed and treated in a custom-made way. With high efficiency and minimal side effects. The prerequisite: Disease mechanisms have to be understood on the molecular level. Enormous research efforts are still required, ensuring an optimal use of research funds and intellectual resources. But PMC is not only about strategic decisions. The partners work on specific joint projects. One example: Long before the disease breaks out Parkinson’s patients show certain symptoms, which are usually ignored at first and only later identified as precursors of the neurodegenerative disease. One of these signs are digestive problems. The scientists suspect that the colon is not properly working because the nerves in the autonomic nervous system are affected - long before the disease damages the brain. »If we can manage to detect first signs on the molecular level leading to Parkinson’s, meaning that we identify biomarkers, we would have made a great deal of progress in early diagnosis,« Rudi Balling states. One research institute alone is overstrained with this task. It can only be mastered in powerful consortia. Luxembourg has taken the lead in this field and has established the Personalised Medicine Consortium (PMC). Taking part are: the Luxembourg Centre for Systems Biomedicine (LCSB), the Intergrated Biobank of Luxembourg (IBBL) and a pilot project on lung cancer, led by the Centre for Public Health Research (CRP Santé). Within the consortium, a lively exchange is taking place: »We talk about the scientific orientation of the institutes,« LCSB director Prof. Dr. Rudi Balling explains, »and how we can coordinate our investments.« To come closer to this aim, the IBBL and the LCSB have launched a research project in which colon tissue from biopsies is systematically analysed. Later the data can be associated to the disease history of the patient - according to privacy rules and respecting personal rights. »When patients that seem perfectly healthy today, develop Parkinson’s Disease in a couple of years, we can search our molecular profiles of tissue samples for molecules that only occur in these people,« says Balling, »And use them as biomarkers for individual Parkinson’s early diagnosis.« This approach is of great importance in times of high-tech research. Research fields like genomics, proteomics or metabolomics need fully automatic labs and large processing capacities that also require considerable investments. 19 Strategic Partnership Learn from the Best Leroy Hood, President of the ISB, is a booster of the cooperation with the LCSB. The LCSB has a close cooperation with the Institute for Systems Biology (ISB) in Seattle. LCSB scientists like Patrick May do their research at the ISB to improve the systems biology know-how at LCSB. »In systems biology, ISB has been a world leader for more than the last ten years,« says Dr. Patrick May, biologist, biochemist and biology information scientist. »And it has since managed to remain on top.« This progress and success was achieved in part by ISB president Leroy Hood who, in the very early stages, began to systematically combine computational biology with the »omics« - genomics, proteomics and transcriptomics. Patrick May explains: »These combinations of varying methods have led to far-reaching scientific progress that in turn accelerates technological development.« Following the motto, »intelligent experiment and advanced analytical methods make for better experiments,« creates a positive feedback loop. The close collaboration between ISB and LCSB is due in part to the direct financial commitments from Luxembourg. »Luxembourg is investing specifically in the sequencing of familial genomes,« says Patrick May. This investment is part of the long-term direction and goal of the LCSB, which is to investigate Parkinson’s Disease. Therefore the ISB’s sequencing project builds up a database to enable the systematic research of the genetics of Parkinson’s Disease. In tandem with this, an exchange of scientists also plays an important role in this collaboration. During the summer of 2011, five LCSB researchers worked in Seattle. Patrick May, who has been in Seattle since May 2010, stayed the longest. »The communication at ISB is quite strong,« is his impression: »We have an environment in which we frequently converse about our research. But also in our free time, there is a sense of togetherness with the various activities we take part in. These intense atmospheres are the basis for the excellent research at ISB,« says May. Patrick May’s research area is systems biology of yeast strains, a topic that at first glance hardly seems connected to the LCSB theme of Parkinson’s Disease. May clarifies: »We know that some of the metabolic pathways of yeasts are also found in higher organisms, such as humans, and that they vary only slightly. Yeast cells are versatile in experiments with an ability to be subjected to varying conditions such as environmental changes and varying components. They are ideal for studying metabolic pathways in biological systems.« With this, LCSB gives an important impetus for ISB, Patrick May states: »We are bringing in the approach to understanding human diseases. We are now examining certain metabolic pathways in yeast cells, which are similarly found in humans and are also related to human diseases.« Through this approach researchers can increase the chance, for example, of finding bio-markers that could later be used to diagnose Parkinson’s Disease. And possibly also to be able to more closely see the genetic origins of the disease piece by piece: »Yeast cells undergo an incredible amount of genetic mutations which could be used to find connections with Parkinson’s,« says May. May´s research for LCSB at ISB will continue until early 2012, but he will continue to act as a bridge between the two institutes. He is confident in the continuing collaboration even after the end of the project: »We are bound together by several projects. I can envision on my return journey back to Luxembourg several regular trips between Europe and the USA –a quarter of the year here, a quarter there. This would help to continue and intensify exchange between both Institutes.« Referring to the fact that the thought of so much travel would be exhausting, May replies, »No, we have progressed together so well, that would only be fun for me.« 20 Pupils learning genetics together with Rudi Balling at the LCSB workshop at the »Kanneruni«. International Collaborations LCSB at »Kanneruni« LCSB and the Systems Biology Institute (SBI) in Tokyo, Japan, are jointly working on a deeper understanding of the complex system of Parkinson’s Disease. Prof. Antonio del Sol (LCSB) and Prof. Hiroaki Kitano (SBI) are the principal investigators within this collaboration. Modelling and analysis of biological networks will be used to elucidate disease mechanisms and development. This includes gene regulatory networks, metabolic networks and proteinprotein interaction networks. The use of diverse mathematical approaches should allow a better prediction of how diseases, can be prevented or treated. How do our cells know how to keep us healthy? How is our genetic material set up? And how do genes work? Inquisitive girls and boys have received answers to these and many other exciting questions at a workshop that the LCSB offered at the University of Luxembourg’s »Kanneruni 2010«. The Department of Engineering at the University of Cambridge and the LCSB have signed an agreement for collaboration in research and teaching in the field of Systems Biology. Both parties aim to improve the understanding of biochemical systems, in particular in Parkinson’s Disease. The principal investigators are Jorge Gonçalves of the University of Cambridge and Rudi Balling, both responsible for planning and managing joint activities. Such activities include research projects funded by companies, national government offices, and international bodies, student and staff exchanges, and teaching activities At the event titled »The amazing journey into our cells Where is our body’s instruction manual?« Prof. Rudi Balling, director of the LCSB, and the children built proteins from LEGO blocks. Using an almost two meter-long chromosome model, he eased them particularly well into the actually microscopic medium for hereditary matter. To conclude the event, each child, accompanied by its parents, received a participation certificate handed to them by Prof. Lucien Kerger, the former academic vice-president of the University. Getting children and teenagers excited about the natural sciences is an explicit goal of the LCSB. 21 Media Coverage The LCSB is a great story - for all LCSB members as well as for the media. Scientists from LCSB are regularly meeting journalists to provide latest information on recent research projects and on the development of the centre. Our news result in articles in all Luxembourgish newspapers, in its radio and TV stations. They are published by international media like Frankfurter Allgemeine Zeitung, LaVOIX and distributed by news agencies like dpa. Den Geheimnissen des Stoffwechsels auf der Spur (Tageblatt) Au fil de l´expérience Ausgereifte Pläne und Roadmap (LaVoix) (Luxemburger Wort) Parkinson Symposium at LCSB In November 2010 the LCSB invited to its first Parkinson Symposium in Luxembourg. Luxemburg setzt auf Biomedizin D´Biomedizin zu Lëtzebuerg huet en Numm: Prof. Dr. Rudi Balling (radio 100,7) Thinking big Eine Universität aus dem Boden stampfen (d´Lëtzebuerger Land) This two-day conference attracted stakeholders and worldknown experts in the diverse research field of Parkinson’s Disease (PD). The symposium offered a unique chance for both clinicians and scientists, all international experts in PD, to get a stimulating and vivid exchange of ideas and to establish first links of an efficient network on research on mitochondrial dysfunction in PD. All aspects of basic genomics/proteomics/metabolomics of mitochondria in idiopathic and monogenetic PD forms were intensively discussed and presented the LCSB and Luxembourg for the first time as major future players in the field. The keynote lecture on mitochondria in PD was given by Prof. Dr. Anthony Schapira from London (UK). In future the LCSB will invite to further workshops and symposia on a regular yearly basis to further strengthen international collaborations and knowledge exchange on the highest scientific level. These events will present the opportunities and excellence of science done in Luxembourg to the international scientific community. 22 (Revue Technique) (FAZ) Man gibt mir fünf Jahre Zeit, dann muss alles florieren (Berliner Zeitung) Aus Biologie wird Medizin Das richtige Medikament für den Patienten Luxemburg will Biomarker-Standort werden (VBIO) (Tageblatt) (dpa Europadienst) Individualmedizin erfinden (Luxemburger Wort) Wie? Was? Wann? Wo? Warum? – Mehr wollen wir gar nicht wissen The 140-Mio-€-Plan of a smart small country (EMBO Encounters) 23 (Forum) Report Facts & Figures 2010 LCSB Income (in kEUR) LCSB Personnel Status Name Discipline/Function Professors (Faculty of Science Technology and Communication) Rudi Balling Antonio del Sol Biology Computational Biology Senior Researchers Manuel Buttini Carine de Beaufort Nico Diederich Karsten Hiller Jochen Schneider Reinhard Schneider Nikos Vlassis Paul Wilmes Neuropathology MD-Pediatrics MD Metabolomics MD-Endocrinology Bioinformatics Computer Science, Robotics Ecosystems Biology LCSB-PostDocs at ISB, Seattle Patrick May Evangelos Simeonides Rene Hussong Alexander Skupin Alexey Kolodkin Bioinformatics Systems Control Engineering Informatics Physics Chemical Engingeering PostDocs Paul Antony Tina Binz Enrico Glaab Feng He Wiktor Jurkowski Ming Miao Alessandro Michelucci Emilie Muller Paola Pozzo Kirsten Roomp Pranjul Shah Jie Zhang Neurobiology Metabolomics Bioinformatics Chemical Engineer Chemistry-Bioinformatics Biochemistry Neurobiology Ecosystems Biology Bioinformatics Bioinformatics Ecosystems Biology Metabolomics PhD students Thekla Cordes Isaac Crespo Hugo Roume Aravind Tallam Christophe Trefois André Wegner Metabolomics Bioinformatics and Computational Biology Ecosystems Biology Bioinformatics Computer Science-Engineering Metabolomics Operating expenses Scientific Support Aidos Baumuratov Serge Eifes Imaging, Bio-Physics Bioinformatics Investments Technical Support Nicolas Bonjean Olga Boyd Annegraet Daujeumont Jenny Ghelfi Abhimanyu Krishna Sandra Koeglsberger Laura Lebrun Overall Lab Coordination Experimental Biology Experimental Biology Metabolomics Bioinformatics Experimental Biology Ecosystems Biology Project Management Regina Becker Julia Kessler Jasmin Sinha Strategy Development Scientific Coordinator Project Coordination Administrative and Support Staff Veronique Briche Katrin Effenberger Aurélia Giovannangeli Zino Hemgesberg Anke Vogler Secretary Human Ressources Secretary Facility Management Controlling 90 (1%) 629 (10%) Ministry of Research and Higher Education University of Luxembourg Knowledge Transfer Programme with ISB Fonds National de la Recherche (FNR) 1,800 (28%) 4,000 (61%) 2010 LCSB Expenses (in kEUR) 15 (1%) 1 (0%) 83 (4%) 124 (7%) Wages 648 (34%) Sub-contracting Travel 507 (27%) Repres. and Registration 522 (27%) 24 Documentation 25 Categories of Professional Staff LCSB International Grants 7% Project Name Programme Project Coordinator LCSB PIs Start date of project IT FoM (Future of Medicine) FP7 - FET ICT Hans Lehrach (Berlin) Rudi Balling 01.05.2011 EpiPGX FP7 - HEALTH Sanjay Sisodiya (London) Rudi Balling Antonio del Sol Reinhard Schneider 01.11.2011 Beta-JUDO FP7 - HEALTH Peter Bergsten (Uppsala) Reinhard Schneider 01.01.2012 HICE HGF (D) Ralf Zimmermann (Munich) Karsten Hiller 01.01.2012 CoGIE ESF - EUROCORES Holger Lerche (Tübingen) Rudi Balling Antonio del Sol Reinhard Schneider tbd SYSGENET COST Klaus Schughart (Braunschweig) Rudi Balling tbd Activity or Candidate FNR code Start date of project Visiting Scholar Jorge Gonçalves (UK) AM2c 15.06.2010 Karsten Hiller ATTRACT 15.09.2010 Symposium on Parkinson‘s Disease AM3 19.-20.11.2010 Ecosystems Biology AFR PostDoc 01.09.2011 Metabolomics AFR PhD 01.09.2011 Biomedicine Gala AM* 26.09.2011 Researchers 9% Technicans PhD students 13% Administratives Other Staff 13% Nations represented at LCSB LCSB FNR Grants 58% Interim Board LCSB Nation Participants 2010 Belgium Rolf Tarrach President University of Luxembourg 1st International Biomedicine Symposium AM3 27.09.2011 Canada Eric Tschirhart Director of Administration University of Luxembourg Ecosystems Biology AFA PhD Student 01.10.2011 China Luciënne Blessing Vice-president University of Luxembourg (Research) Paul Wilmes ATTRACT 01.10.2011 Paul Heuschling Dean of Faculty of Science, Technology and Communication (FSTC) Ecosystems Biology AFR PostDoc tbd Visiting Scholar Piotr Gawron (Pl) AM2c tbd France Germany Greece India Italy Meetings and Workshops (co)organised by the LCSB International Cooperation Agreements Luxembourg Date Event In cooperation with Institution Activity The Netherlands 19.-20.11.2010 Symposium on Parkinson‘s Disease (Luxembourg) CHL Cambridge (UK) Knowledge Transfer Poland 10.-11.01.2011 Workshop CSC-LCSB-LSRU (Chateau Schengen) CSC CRP-Santé (L) Proteomics Russia 26.-27.09.2011 Belval building Opening Ceremony and Symposium HZI (D) Mouse Models 28.-29.09.2011 Workshop Personalised Medicine: Metabolic Disruption and Disease SBI (J) Network Reconstruction TGen (USA) Genomics Spain Switzerland IBBL USA 26 27 Publications 2010/11 2010: 1. Morgan, H., Beck, T., Blake, A., Gates, H., Adams, N., Debouzy, G., Leblanc, S., Lengger, C., Maier, H., Melvin, D., Meziane, H., Richardson, D., Wells, S., White, J., Wood, J.; EUMODIC Consortium, De Angelis, M.H., Brown, S.D., Hancock, J.M., Mallon, A.M. (2010) EuroPhenome: a repository for high-throughput mouse phenotyping data. Nucleic Acids Res. 38, D577-581 2. Balling, R. & Becker, R. (2010) EATRIS Infrastructure accelerates translation. BIOforum Europe pp 2-4, 1-2/2010 3. Probst-Kepper, M., Balling, R. & Buer, J. (2010) FOXp3: required but not sufficient. The role of GARLP (LRRC32) as a safeguard of the regulatory phenotype. Curr. Mol. Med. 10, 533-539 4. Smedley, D., Schofield, P., Chen, C.K., Aidinis, V., Ainali, C., Bard, J., Balling, R., Birney, E., Blake, A., Bongcam-Rudloff, E., Brookes, A.J., Cesareni, G., Chandras, C., Eppig, J., Flicek, P., Gkoutos, G., Greenaway, S., Gruenberger, M., Hériché, J.K., Lyall, A., Mallon, A.M., Muddyman, D., Reisinger, F., Ringwald, M., Rosenthal, N., Schughart, K., Swertz, M., Thorisson, G.A., Zouberakis, M., Hancock, J.M. (2010) Finding and sharing: new approaches to registries of databases and services for the biomedical sciences. Database (Oxford) 2010:baq014 5. Schughart, K. & SYSGENET consortium. (2010) A meeting report from a new European network for systems genetics. Mamm. Genome 21, 331-336 6. Del Sol, A., Balling, R., Hood, L. & Galas, D. (2010) Diseases as network perturbations. Curr. Opin. Biotechnol. 21, 566-571 10. Moussay, E., Wang, K., Cho, J.H., van Moer, K., Pierson, S., Paggetti, J., Nazarov, P.V., Pallssot, V., Hood, L.E & Galas, D.J. (2011) MicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. (USA) 108, 6573-6578 11. Antony, P.M, Diederich, N.J. & Balling, R. (2011) Parkinson´s disease mouse models in translational research. Mamm. Genome (in press) 12. Kolodkin, A., Boogerd, F.C., Plant, N., Bruggeman, F.J., Goncharuk, V., Lunshof, J., Moreno-Sanchez, R., Yilmaz, N., Bakker, B.M., Snoep, J.L., Balling, R. & Westerhoff, H.V. (2011) Emergence of the silicon human and network targeting drugs. Europ. J. Pharmaceutical Sciences (in press) 13. Bousquet, J., Anto, J.M., Sterk, P.J., Adcock, I.M., Chung, K.F., Roca, J., Agusti, A., Brightling, C., Cambon-Thomsen, A., Cesario, A., Abdelhak, S., Antonarakis, S.E., Avignon, A., Ballabio, A., Baraldi, E., Baranov, A., Bieber, T., Bockaert, J., Brahmachari, S., Brambilla, C., Bringer, J., Dauzat, M., Ernberg, I., Fabbri, L., Froguel, P., Galas, D., Gojobori, T., Hunter, P., Jorgensen, C., Kauffmann, F., Kourilsky, P., Kowalski, M.L., Lancet, D., Pen, C. L., Mallet, J., Mayosi, B., Mercier, J., Metspalu, A., Nadeau, J. H., Ninot, G., Noble, D., Oztürk, M., Palkonen, S., Préfaut, C., Rabe, K., Renard, E., Roberts, R. G., Samolinski, B., Schünemann, H. J., Simon, H.U., Soares, M. B., Superti-Furga, G., Tegner, J., Verjovski-Almeida, S., Wellstead, P., Wolkenhauer, O., Wouters, E., Balling, R., Brookes, A. J., Charron, D., Pison, C., Chen, Z., Hood, L., Auffray, C. (2011) Systems medicine and integrated care to combat chronic non-communicable diseases. Genome Medicine (in press) 2011: 7. 8. 9. 14. Jurkowski, W., Roomp, K., Crespo, I., Schneider, J. G., Del Sol, A. (2011) PPARγ population shift produces disease-related changes in molecular networks associated with metabolic syndrome. Cell Death Dis. 2011 Aug 11;2:e192. doi: 10.1038/ cddis.2011.74. Abrahams, J.P., Apweiler, R., Balling, R., Bertero, M.G., Bujnicki, J.M., Chayen NE, Chène P, Corthals GL, Dylag T, Förster F, Heck AJ, Henderson PJ, Herwig R, Jehenson P, Kokalj SJ, Laue E, Legrain P, Martens L, Migliorini C, Musacchio A, Podobnik M, Schertler GF, Schreiber G, Sixma TK, Smit AB, Stuart D, Svergun DI, Taussig MJ. (2011) 4D Biology for health and disease. N. Biotechnol. 291-293 15. Vlassis, N., Ghavamzadeh, M., Mannor, S., and Poupart, P. (2011) Bayesian Reinforcement Learning. In Reinforcement Learning: State of the Art. M. Wiering and M. van Otterlo (eds.), Springer, 2011. (in press) Pavlopoulos, G.A., Secrier, M., Moschopoulos, C., Soldatos, T.G., Kossida, S., Aerts, J., Schneider, R. & Bados, P.G. (2011) Using graph theory to analyze biological networks. BioData Mining doi:10.1186/1756-0381-4-10 University of Luxembourg | Luxembourg Centre for Systems Biomedicine | 7, avenue des Hauts-Fourneaux | L-4362 Esch-sur-Alzette T. + 352 / 46 66 44-6973 | E-Mail [email protected] | www.uni.lu/lcsb 16. Roach, J.C., Glusman, G., Hubley, R., Montsaroff, S. Z., Holloway, A. K., Mauldin, D. E., Srivastava, D., Garg, V., Pollard, K. S., Galas, D. J., Hood, L., Smit, A. F. Chromosomal haplotypes by genetic phasing of human families. Am J Hum Genet. 2011 Sep 9;89(3):382-97. Schneider, J.G., Amend, S.R. & Weilbaecher, K.N. (2011) Integrins and bone metastasis: Integrating tumor cell and stromal interactions. Bone 48, 54-65 Realisation and Text: scienceRELATIONS, Dortmund/Berlin, Germany | Layout: www.spezial-kommunikation.de All photos: Dirk Hans, scienceRELATIONS. Except: Linda Blatzek Photography (Cover, 17); fotolia.de (7); blitz.lu (19: Bob Phillips); Michel Brumat (11: del Sol, 14, 15); ISB (20); LCSB, Dr. Aidos Baumuratov, Dr. Paul Antony (7: neurons), miikkaheinonen.com (19: Guy Berchem), Petra Svoboda, UL, (13: Hiller) 28 www.uni.lu/lcsb