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European Systems Biology Initiative; Genomics in the service of Health (ESBIGH)

Description dated June 7, 2002

Summary

 

Subject of this "Expression of Interest" (EoI) is the establishment of a pan-European "Supra Network of Excellence" (SoE) to maximise the benefits to human health from Systems Biology (SB) and functional genomics. The SoE will unite and permanently integrate various "Networks of Excellence" (NoE), Integrated Projects (IP), as well as other recently initiated national programmes (NP) dedicated to SB. As the function of all living cells depends upon dynamic interactions between all cellular macromolecules (i.e. proteins, DNA, RNA), a molecule-to-system approach will greatly enhance the understanding of the human organism and its diseases and will enable the effective exploitation of genomics for the improvement of human health. Multidisciplinary research is necessary to translate the data accumulating from genomics into applications of molecular medicine. Accordingly, the incorporation of SB into genomics is multifaceted and cannot be covered by a single NoE. Several NoEs, IPs and large-scale NPs, each devoted to well-defined aspects of SB, will therefore be integrated in an overall context called the "European Initiative on Systems Biology in the Service of Genomics and Health" (ESBIGH). ESBIGH will bring about maximum synergy between the individual SB modules through the transfer and integration of data and know-how, the sharing of common databases, the organization and funding of cross-connecting research activities, a common teaching programme and the establishment of general Standard Operating Procedures (SOP).
This integrative approach is unique world-wide and will place Europe at the forefront of both Systems Biology and medically-oriented applied functional genomics.

 

ESBIGH Mission

ESBIGH will catalyse the integration of all the first rate European expertise available in SB to explore the full potential of genomics for human health. It will open up novel perspectives in the diagnosis, prevention, monitoring, and treatment of human diseases. The ESBIGH SoE will provide tools for the study of, and for the development of improved therapies for human disorders, including monogenic and multifactorial diseases, such as those caused by a combination of genetic and environmental factors. ESBIGH will also engage in implementing those tools in corresponding studies at (pre)clinical and biotechnological stages. ESBIGH will help to integrate experimental SB (functional genomics) with theoretical SB (mathematical biology/integrative bioinformatics). ESBIGH will also promote the optimisation of biotechnological processes in industry, thus contributing to the high-yield production of recombinant pharmaceuticals and to sustainable production processes. ESBIGH will strongly promote the training of young scientists by coordinating European graduate schools and courses. Following the initial period of EC funding for ESBIGH networking, a suitable platform will be established for a European non-profit organisation on SB for genomics and health. This non-profit organisation will be financially independent through membership fees from companies and the licensing of expertise and technologies.

 

Advanced Genomics for Health: What Do We Know about Genomics, Life and Health?

The complete sequencing of genomes from several organisms has generated a mass of information unimaginable just a few years ago. The majority of cellular components (macromolecules) of living cells and organisms, including man, are now well-understood at the DNA level. Despite these tremendous achievements, we are still a long way from solving the puzzles of life and still fail to understand complex living systems as wholes - a knowledge which could allow us to cure most diseases. Although we are confronted with severe and life-threatening diseases such as cancer, diabetes and cardio-vascular disorders, we fail to provide effective diagnosis and therapies in many instances. At this point, we are just collecting the parts of the puzzle (whole-genome sequences) and, although we know the structure and the sequence of genes, many associated functions remain to be discovered. Hence, functional genomics and molecular biochemistry are needed to unravel the functions of the single components in the context of living cells.
Assuming that we knew the shape and function of every cellular macromolecule, would we then understand life, and would this understanding bring us closer to causal therapies for remaining diseases? The answer will certainly be disappointing as long as we keep ignoring very important aspects. Imagine a list of all the components of a TV set and their individual technical data. Would this information be sufficient to understand how the whole TV set works? Obviously not, as long as the wiring (i.e. the interconnections of all the electronic parts) is unknown. A single misconnection can cause a TV to fail. Similar additional information about the connections is indispensable in order to understand how complex biological systems such as living cells work. In other words, knowing how the macromolecules are connected and how that specific connectivity generates biological functions will provide a key to the understanding of life. This idea is the driving force behind a newly emerging multidisciplinary scientific discipline termed Systems Biology. It was recently identified as a "hot topic" in the media, perhaps due to the general understanding that we are entering a new era in biology, involving scientists who are seeking the fundamental mechanisms that control the phenomena of life and health, as well as lead to the occasional failure of biological processes, i.e. disease.
Systems Biology (SB) thus focuses on the real time study of the organisation and functional interaction of all molecules in living cells and organisms. In the past, SB was hampered by a lack of sufficient molecular data on living organisms. During the last decade, this situation has dramatically improved due to the immense increase in the (i) rate at which such data are generated, (ii) completeness of the dataset (e.g. whole transcriptomes rather than bands on a Northern), and (iii) the progress in information technologies that brought about the development of superior methods and computer tools for pathway simulation, data storage and processing. The next quantum leap in biomedical research will be achieved by joining these data and tools in a multidisciplinary, experimental plus mathematical, SB approach. That approach will embrace different concepts and expertise from fields like molecular biology, biophysics, biochemistry, genomics, informatics, mathematics, systems engineering and molecular medicine. This "Systems Biology meets Genomics" approach will pave the way to a better understanding and the successful treatment of human diseases. Therefore, this proposal is dedicated to a European Initiative on Systems Biology in the service of Genomics and Health (ESBIGH).

 

Systems Biology for Genomics and Health: Networking European Excellence

Europe holds a strong and propitious position in the field of SB and its implementation in functional genomics because it can rely on excellent and research expertise in the biosciences. SB evolved as a branch of theoretical biology and is just beginning to blossom in Europe, reviving major research traditions in areas such as self-organisation, metabolic control and non-equilibrium thermodynamics/bioenergetics. Bioinformatics and mathematics are also based on solid scientific fundaments throughout Europe. However, Europe has not yet become a common research area. At present, the lack of coherence between diverse national scientific programmes hampers effective concerted actions and the integration of the European research community as a counterbalance to the dominant US scientific community. Notably, several US institutions and national initiatives are dedicated to SB, some of which focus on human health (e.g. Institute for Systems Biology in Seattle).
Indeed, many European countries are excellent with regard to individual technologies related to SB, but none of them does well in all the SB fields that need to be integrated to make SB work for Genomics and Health. Thus, we propose to link the top European expertise in SB relevant to functional genomics through a SoE termed ESBIGH. This SoE will integrate and exploit the "data pool" of genomics, the multidisciplinary approach of SB and the intensive use of novel effective platform technologies (i.e. transcriptomics, proteomics, metabolomics, bioinformatics, functional genomics). The strength of this novel branch of research is the joining of forces of different scientific disciplines: It is generally accepted today that substantial progress can be made at the intersections of different scientific disciplines. We expect many tremendous scientific and economic benefits, e.g. through in silico models of major biological phenomena in living cells and organisms (artificial models of life), from the synergistic strength of such a SoE. The outcome of ESBIGH will be relevant for applied science and industrial applications in biotechnology and molecular medicine. Virtual cells for example will facilitate drug development, studies on drug metabolism and drug detoxification will reduce animal experiments. The biotech and pharmaceutical industries (both SME and big pharma) will participate as cooperation partners in ESBIGH. ESBIGH will also implement an industrial platform, providing for the rapid transfer of know-how to biotechnology applications. ESBIGH will also help manage individual intellectual property rights of its partners.

 

ESBIGH: A Network of Networks

The integration of pan-European research is beneficial given that only the outstanding expertise of each country is recruited and actively involved in the network. Most of the coordinators of the EoI involved in ESBIGH are renowned scientists from the different fields relevant to SB and genomics. The active support and general interest of all these scientists in the idea of ESBIGH - confirmed in the Annex - indicates that Europe is ready to think and act in a multidisciplinary mode at a systems-level! We therefore propose to follow a unique and ambitious approach with ESBIGH: European NoEs, IPs and NPs will each focus on their own identifiable modules of SB relevant for medical genomics and molecular medicine. If these NoEs were to act as individual consortia, most of the results and conclusions from these networks would probably remain "hidden" from the scientific community and potential applicants (except for publications in peer journals and EU reports). In contrast, ESBIGH will create synergy between the different NoEs, providing the necessary infrastructure to collect, present and transfer findings to other networks and scientists not directly involved in the SoE by means of a web-based platform, printed materials, electronic newsletters, scientific consultancy by ESBIGH coordinators, and frequent ESBIGH meetings.
One of the most important and demanding challenges for SB is the requirement to satisfy the need for standardised data through standard operating procedures (SOP). It is absolutely mandatory that data are reproducible and thus suitable for modelling and computer-based simulation. ESBIGH will therefore offer workshops to provide training on essential requirements of data collection, processing and other techniques relevant for SB. ESBIGH will coordinate and cooperate with individual NoEs to start sharing expertise, protocols and software platforms from an early stage. This joint approach will be unique and highly beneficial for all participating teams, but also for the general scientific community in related fields. Hence, ESBIGH will establish central databases that will be freely accessible to the entire scientific community. In this context, ESBIGH will provide know-how and experience emanating from the participating NoEs and large NPs. Furthermore, by bringing together the very best scientists in the field of SB and genomics, ESBIGH will set up SOPs for SB which ensure standardised protocols and high quality data of the utmost reproducibility. The individual NoEs, IPs and NPs that are partners in ESBIGH will focus on their own areas of SB for genomics and health. An essential activity of ESBIGH is therefore to organise communication and integration between these areas and between individual areas and applications. ESBIGH will accomplish this through regular calls for proposals, evaluations and funding for/of research activities that bridge the participating NoEs, IPs and NPs.
Finally, ESBIGH will also emphasise the integration and promotion of young scientists in(to) the ESBIGH area through training networks, dedicated European graduate schools, and continuous student exchange among various NoEs and research teams. SB for genomics and health is an attractive research topic for PhD students and postdocs from various disciplines. ESBIGH will organise seminars, workshops, as well as student lecture courses through established European granting agencies such as FEBS, NATO and EMBO and, of course, the EC on a regular basis.

 

Partners in ESBIGH

The essence and explicit aims of ESBIGH are simple: It will create added value for advanced genomics in the context of human health by creating synergy between the NoEs, IPs and NPs. ESBIGH will remain open to new NoEs and IPs and will even catalyse the formation of new NoEs and IPs. ESBIGH will actively invite interested researchers, research institutions and other suitable organisations, on the premise of their excellent research performance. The structure of ESBIGH will facilitate the continuous integration of partners because each "member consortium" acts in parallel as an autonomous module. The criteria for including a new NoE in ESBIGH will be (i) its importance for Systems Biology, (ii) its importance for the routes from Genomics to human health, (iii) its scientific excellence, and (iv) likely synergy with the other NoEs in ESBIGH. This way, ESBIGH will not only serve as a "crystallisation nucleus" for further activities, but will also detect deficiencies that prevent the appropriate development of SB for Genomics and Health. Essential aspects of ESBIGH include:

  • Integrative Genomics, i.e. parallel acquisition of diverse parameters relevant for genomics (i.e. the "expressome", the transcriptome, the proteome, the metabolome and the physiome of living cells) because cell function requires integration of all of these.
  • Complex Systems, focusing on the emergence of new properties from the non-linear interactions of molecules
  • Entering the Living Cell, focusing on the experimental determination of molecular properties inside living cells.
  • Integrative Bioinformatics, combining all data of the above experimental strategies with those from databases to calculate relevant implications.
  • Silicon Life, i.e. making computer replica of living cells and organisms.

The Annex lists prospective NoEs and IPs which will join ESBIGH if they can acquire sufficient EC funding. In addition to EC-funded NoEs and IPs, large national SB programmes and institutions will participate in the SoE. Examples of such integrated national initiatives include the Amsterdam Silicon Cell and the German "Systems of Life - Systems Biology".

 

Tasks of ESBIGH

 

  • Create synergy between the European networks and national initiatives on SB
  • Focusing European Systems Biology on genomics and health
  • Organisation of research to stimulate synergy between IPs, NPs and NoEs
  • Organisation and funding of projects to bring SB closer to application in human health
  • Window function to industry and non-European research
  • Training of a new generation of students in SB for genomics and health.
  • Attracting mathematicians, bioinformaticians, biologists and clinicians to SB for Genomics and Health

 

Organisation of ESBIGH

ESBIGH will be based on clear, manageable and open organisational structures. First, the Scientific Steering Committee (SSC) will be the independent, decision-making panel of international (European) experts that will supervise, control and coordinate the SoE. The SSC supports the successful establishment and development of ESBIGH. One SSC member will be appointed by the EC, three members by the scientific advisory board (see below), and one member by the industrial partners. The SSC will elect a chairperson out of its own ranks for each period of three years.
Second, the Scientific Advisory Board (SAB) will consist of the coordinators of the participating NoEs, IPs, NPs and industrial biotechnology partners. This board will meet twice a year and discuss the general and most important results, problems and methodologies that arise from the participating networks and initiatives. SAB members should be accompanied by junior staff, who present the most recent research results. SAB members will discuss special topics in more detail (e.g. standardisation, SOP, IP, training, etc.) within the framework of separate workshops. Results of workshops will be communicated to the SSC and placed on the web. On the basis of conclusions from these meetings, integration projects will be redirected, public calls for new proposals for IPs and projects formulated, and external groups invited to join ESBIGH. As possible in FP6, ESBIGH will announce dedicated calls for proposals. The board will discuss funding of research proposals submitted after the calls, using external peer review to provide an objective basis. The final decision will be made by the SSC.
Finally, the Organisational Board (OB) will consist of the coordinators from the three (or more) core institutions involved in the technical organisation of the SoE. The members will take care of the technical and financial aspects of ESBIGH. They will meet regularly with representatives of the Scientific Advisory Board, the Scientific Steering Committee and the EC. The following institutions, all of whom are experienced in the project management of large scale research programmes, will serve as these ESBIGH core institutions:

 

Training and Teaching within ESBIGH

 

The teaching of SB for genomics and health will be organised in three modes and co-ordinated by an ESBIGH teaching committee to be appointed by the SSC:
1. European Graduate schools on ESBIGH. These will be formed by integrating existing national research schools on the topic. The first such school is already in existence, i.e. the European Graduate school BCA-GKB, between the BioCentrum Amsterdam and the Graduierten Kolleg Berlin-Dynamics and Evolution of Cellular Processes, funded by NWO and DFG.
2. Transnational courses.
3. Short-term (2-4 week) training and research training of up to six months for graduate students and postdocs from one research group or another within ESBIGH.

 

The Set-Up Phase of ESBIGH

The preliminary scientific co-ordination of ESBIGH resides with a small transnational committee whose members include Roland Eils (mailto:r.eils@dkfz.de?subject=ESBIGH) of the German Cancer Research Center, Heidelberg, Karl Kuchler (mailto:kaku@mol.univie.ac.at?subject=ESBIGH) of the University and BioCenter of Vienna, and Hans V. Westerhoff (chair pro tempore; mailto:hw@bio.vu.nl?subject=ESBIGH) from the BioCentrum Amsterdam. Responsibility for the secretariat will be with Jens Doutheil at the Dechema in Frankfurt. It is the explicit aim of ESBIGH to unite most if not all European groups whose work is excellent in the ESBIGH area, as well as a number of junior groups expected to develop towards such excellence. Interested groups, IPs, NoEs, and NPs are requested to contact Dr. Doutheil (mailto:doutheil@dechema.de?subject=ESBIGH).

All members of the preliminary transnational ESBIGH coordination team are also members of the Steering Committee of the German SB initiative, thus allowing an effective transfer of know-how and experience between the German approach and ESBIGH. They are also members of other such Steering Committees in the EU. The BMBF welcomes and encourages a common European SB approach and supports the integration of the "Systems of Life - Systems Biology" competence network into ESBIGH. It will contribute to the improved convergence and durable integration of national funding activities offering a "communication platform" between political and scientific stakeholders throughout Europe.

 

Annex: Composition of ESBIGH

Participating European NoEs, IPs and other national initiatives include:

(1) Participating European Networks (NoE) and Integrated Projects (IP). Inspecting the Expressions of Interest (EoI) submitted for the FP 6 before June 9, 2002, ESBIGH will contact all coordinators of EoIs related to system biology to see if they will submit an FP6 program proposal and whether they will want to link that to ESBIGH. Based on records of excellence, research plan, perspective of applicability, and sufficient representation of minority and junior excellent scientists, system biology consortia will be selected and asked to participate in ESBIGH. At present the following consortia have spontaneously expressed interest in teaming up through ESBIGH:

- FEPACS: Fuel Ethanol Production from Alternative Carbon Sources (Richard, Helsinki, FI) IP

- YSIC, Yeast Silicon Cell (Alberghina, Milano/Westerhoff, Amsterdam I/NL) IP

- 3D Genomics (Van Driel, Amsterdam; NL) IP

- Hierarchical Concepts (Gilles, Magdeburg, DE) IP

- Virtual Biotechnology: in Silico Simulations of Cells and Animals as Novel Tools for Biology and Toxicology (VISION) (Moore & Allen, Plymouth, UK) IP

- Omics united; a systems biology perspective from the genome to the physiome (Wolkenhauer, Manchester, UK) IP

- Biosimulation - A New Tool for Drug Development (Mosekilde, Lyngby, DK) NoE

- Nerve Cell Simulation (Cattaneo, Arisi, Rome, IT) IP

- ABC-RescEU (Kuchler, Vienna, AT) IP

- Microgravity and Life Sciences (Jack van Loon, Amsterdam, NL) NoE

- BioTools (Hans Söderlund, FI) NoE

- ESBCC: European alliance for Systems Biology applied to Cell Division and Cancer (Serrano, Barbacid, Wodak, Heidelberg, Madrid, Brussels, DE, ES, BE) IP

- From the virtual cell to the real patient (De Meyts, Novo Nordisk, DK) IP

- Building an integrated network of open source, compatible bioinformatics databases and tools enabling Systems Biology (Martin Kuiper, Gent, BE) NoE

- Interaction Proteome. Functional Proteomics: towards defining the interaction proteome (U. Hartl/A K. Werenskiold, Martinsried, DE) IP

- Cellular Signaling Networks in Tumor Biology and Immunology (Höfer & Heinrich, Berlin, DE)

- Cellicium. From bio-array imaging to morphogenesis (Demongeot, Grenoble, FR) NoE

- CROWD. Proteins in cells: structure, folding and interactions in crowded environments (Miquel Pons, Barcelona, ES) IP 

- DYNAMO. Platforms for Monitoring of Dynamics of Cellular Processes (Ruzgas/Emnéus/Owman, Lund, SE) IP

- EUTERS. Environment for Unifying Theoretical and Experimental Research in Systems biology (Ursula Kummer/Rebecca Wade, Heidelberg, DE) IP

- STYFF. Signal Transduction in Yeasts and Filamentous Fungi (Johan Thevelein, Leuven, BE) NoE

- E-Plant. European Plant Systems Biology Network (Ferda Mavituna, Manchester, UK) NoE

- PROTEUS. Functional genomics of the symbiotic and pathogenic alpha proteobacteria (Jean-Jacques Letesson, Namur, BE) IP

 

(2) Contributing national initiatives (NPs) include:

The Amsterdam-centered Silicon Cell (SiC) programme is based on funding from various Dutch sources. It aims at the generation of precise replica of living cells and living organisms. It takes the strategy of first focusing on the better defined pathways and aspects of living cells, such as glycolysis, dynamic spatial heterogeneity in signal transduction around the E. coli PTS, temporal heterogeneity and dynamics in the cell cycle, and the energetics of DNA structure and gene expression. Although most of the result is in silico, most of the activity of the programme is in wet-lab experiments, in acquiring data that are not yet available in literature, or in validating such data. SiC also provides a web-based model 'data' base, in which in silico replica made by this initiative and other similar initiatives all over the world are made fully operational and ultimately integrated into replica of larger parts of living cell.

The German "Systems of Life - Systems Biology" funding activity was recently implemented within the biotechnology framework programme by the Federal Ministry of Education and Research (BMBF). The German SB initiative complements current BMBF programmes on genomics, proteomics and bioinformatics. It intends the early establishment of SB in Germany. The BMBF supports multidisciplinary research teams integrated in a competence network with a focus on the human hepatocyte. Participating groups consist of scientists from German universities and other research institutions, both SMEs and large pharmaceutical companies. Data will be shared between all partners and stored in central databases.

The UK Network for Systems Theory and Genomics (Genetic Systems), funded by the EPSRC and coordinated by Olaf Wolkenhauer.

The Swedish national systems biology initiative, coordinated by Stefan Hohmann, Gotheborgh

The French CNRS National program « Energy from Biomass », coordinated by Gerard Goma, Toulouse

The French network ARC CPBIO. Cooperative Research Initiative on Biological Processes and Process Calculi

oordinated by François Fages, INRIA Rocquencourt, FR

The Greek National Initiative on Structural Genomics coordinated by Mike Kokkinidis, Crete, GR

 

 

(3) Interested individual research groups/institutes.

ESBIGH has received expressions of interest of various individual institutes and research groups that should like to contribute to ESBIGH. ESBIGH however is meant to be a consortium of consortia of research groups (i.e. of IPs, NoEs and NPs). Individual groups and institutes should therefore associate to ESBIGH through one of the consortia that affiliate to ESBIGH. ESBIGH will help catalyze this association by mediating between consortia and groups. A list of interested such groups can be obtained by clicking here.

 

 (4) Companies

 The companies supporting or involved in the IPs, NoEs and NPs that compose ESBIGH (see above) will be invited to take part in the industrial board of ESBIGH. A smaller number of companies will participate more directly in the steering of ESBIGH. At present several companies (both large multinationals and SMEs) are interested in this role. For further information please contact the ESBIGH team.

 

(5) Non-profit organizations

Non-profit organizations such as public research institutes or evaluation centers have expressed their interest to join ESBIGH.