European drive for post-genomic research: European Commission awards €39.4 million to three large-scale projects

Brussels, 19 March 2002

In a drive to gear up research on genomics - the study of genes and their function - the European Commission has awarded €39.4 million to three large research projects. The funding is a prelude to the €2.2 billion earmarked for "genomics research for human health" in the next Community research programme to be launched later this year.

The projects on the genetics of twins, mouse genomics and structural proteomics are demonstrating the new way in which the Commission will fund research in the future: asking scientists from industry and academia to compose top teams from across Europe to conduct research at the cutting edge of science in a selected number of fields and giving them sufficient means to achieve critical mass and world-class excellence.

This effort is part of the European Commission's commitment to invest more and better in the creation of knowledge and to build a coherent European Area for Research and Innovation, as called for by Heads of State and Government at their Barcelona summit two days ago.

For Research Commissioner Philippe Busquin "The decoding of the human genome opens new opportunities for researchers to understand the genetic origins of diseases and to develop new therapies. It is vital for Europe to play a leading role in genomic research and biotechnology, the new frontier of the 21st century.

But we can only use its vast potential for improving our quality of life and Europe's competitiveness if we are better organised across Europe to meet scientific challenges that go beyond the capacities of individual countries."

The three projects funded are the following:

Studies of European volunteer twins to identify genes involved in common diseases, co-ordinated by Prof. Leena Peltonen, Helsinki, Finland.

Because of their identical genetic make up, twins represent an invaluable group for medical researchers to search for the potential genetic origins of common diseases. If it is seen with identical twins that both develop the same common disease in later life, this is a good indicator of a genetic basis for that disease.

This information together with the knowledge of the genome sequence will allow researchers to link gene sequences with disease.

Identifying and understanding these genes opens the way for development of new diagnostic tools and new therapies. By networking the major "twin registries" of Europe and the top researchers in the field, this European project will considerably increase the chances of identifying the genetic origins of common diseases such ascardiovascular disease. Proposed EU funding €13.4 million (see annex 1 for further information).

Understanding human disease through mouse genomics, co-ordinated by Prof. Steve Brown, Harwell, UK and Prof. Pierre Chambon, Strasbourg, France.

The mouse genome is 95 % identical to the human genome and so mice with genetic diseases are potentially very good models for the equivalent human diseases. These models are essential to develop and test potential new treatments for human diseases. In Europe, researchers have isolated mice that develop diseases like those seen in humans. However, to confirm the similarity between murine and human diseases, a large effort is needed for an in-depth analysis of each mouse strain. This project aims to analyse in detail the large number of mouse mutants already available, so that the best mouse model for a specific human disease can be efficiently identified. Another outcome of this European co-operation will be a reduction in the number of animals used in research. Proposed EU funding €12.3 million (see annex 2 for further information).

Structural proteomics in Europe, co-ordinated by Prof. David Stuart, Oxford, UK and Prof. Dino Moras, Strasbourg, France.

Genes code for proteins and together proteins carry out all the biological processes of life. Knowledge of the three dimensional (3D) structure of a particular protein is essential to predict its functions. The structure/function analysis of normal proteins and proteins linked to disease is also of crucial importance for the pharmaceutical industry to develop new drugs. However, the determination of a protein structure is a lengthy and costly process requiring major equipment, infrastructures and know-how. This European project will speed up the structure determination process by optimising each step for high throughput, such as protein production, purification, crystallisation and structure analysis. The structures of more than 600 proteins of medical interest will be identified. Proposed EU funding €13.7 million (see annex 3 for further information).

Through their size and scope and the world-class research teams involved, these projects will lead to substantial advances in understanding the links between the human genome and diseases, strengthen Europe's position in this important field of research and eventually benefit patients. In addition, the new features of these projects, their integrated nature and size make them useful precursors to two of the "new" instruments, notably the integrated projects and the networks of excellence, proposed for the forthcoming Sixth Framework Programme (2002-2006). The novel procedure used to prompt, evaluate and select these projects is described in Annex 4.

· For further information concerning the projects, please contact:

Jacques Remacle, Scientific Officer, Quality of Life Programme, Research DG
Tel : +32-2-296.30.45
E-mail : jacques.remacle@cec.eu.int

Bernard Mulligan, Scientific Officer, Quality of Life Programme, Research DG
Tel : +32-2-296.81.72
E-mail : bernard.mulligan@cec.eu.int

For further information to the press, please contact:

Stéphane Hogan, Press and Information Officer, Research DG
Tel.: +32.2.296.2965 - Fax: +32.2.295.8220
E-mail: stephane.hogan@cec.eu.int

ANNEXE I

Studies of European volunteer twins to identify genes underlying common diseases

Background and objectives of the project: European populations and epidemiological cohorts are of special significance in the current era of genomic research aiming to characterize the background of common human diseases. The genome sequence, detailed information of genetic variations between individuals, high-throughput molecular technologies and novel statistical strategies create new possibilities to define genetic and life-style risk factors behind common health problems. Studies of large population cohorts are needed to transform the genetic information to detailed understanding of the predisposing factors in diseases affecting most human populations. European twin cohorts, containing total of 600,000 twin pairs, combined with top expertise in epidemiology and genetics in Europe, provide a unique competitive advantage for investigations of the role of genetics and environment or life style in the etiology of common diseases. This project will apply and develop new molecular and statistical strategies to analyze unique European twin and other population cohorts to define and characterise the genetic, environmental and life-style components in the background of health problems like obesity, migraine, coronary heart disease and stroke, representing major health care problems worldwide.

What will be the expected benefits for the research field in Europe and for human health? The research of European population cohorts will make an immense contribution to the ambitious objectives set forth for the EC initiative in "Functional genomics and human health". This research project will produce excessive amount of information on the interaction of genetic and environmental factors contributing to human health. The research infrastructure to be built and novel molecular and statistical methods to be developed will facilitate numerous biomedical research programs in Europe in years to come. With the study strategy combining epidemiological, genetic and biostatistical expertise, European research has the possibility of having an impact on genomic research worldwide and contributing specifically to the global understanding of the genetic background of common diseases. The research will provide information of involved genes, and their disease predisposing variants. In future biomedical industry in Europe can capitalize this information in development of novel treatment strategies. Importantly, the understanding of the interactions between genes and environment in the etiology of common diseases can be immediately implemented in European health care and prevention programs.

Training and networking aspects: We will establish a collaborative research network between geneticists, epidemiologists and mathematicians as well as experts in bioinformatics and legal and social issues. We will expand and strengthen the collaboration and integration of molecular epidemiological research in Europe and U.S. and combine special and diverse expertise in the analyses of the European population cohorts. We will build training program for both for pre-and postdoctoral researchers and for more advanced clinicians and scientists to advance their expertise in molecular epidemiology, so essential for the biomedical research of Europe in the 21st century.

The research consortium

Leena Peltonen
(project coordinator)
National Public Health Institute, Helsinki (FI) leena.peltonen@ktl.fi
(tel.: +358-9-4744 8393)

Kaare Christensen University of Southern Denmark KChristensen@health.sdu.dk
Nancy Pedersen Karolinska Institutet (SE) nancy.pedersen@mep.ki.se
Jennifer Harris Nat. Inst. of Public Health (NO) jennifer.harris@folkehelsa.no
Dorret Boomsma Vrije Universiteit Amsterdam (NL) dorret@psy.vu.nl
Jaakko Kaprio University of Helsinki (FI) jaakko.kaprio@helsinki.fi
Antonia Stazi Istituto Superiore di Sanità (IT) stazi@iss.it
Alun Evans University of Belfast, UK a.evans@qub.ac.uk
Ulf Pettersson Uppsala University (SE) Ulf.Pettersson@genpat.uu.se
Ann-Christine Syvänen Uppsala University (SE) Ann-Christine.Syvanen@medsci.uu.se
Lodewijk Sandkuijl Erasmus University (NL) l.a.sandkuijl@lumc.nl

ANNEXE II

Understanding human diseases through mouse genetics

Background and objectives of the project: The completion of the human genome sequence heralds a new era of understanding of the genetic basis of human disease. Determining the function of every one of the 35000 or so human genes and their role in disease will be greatly assisted by the development and characterisation of mouse models of human disease. However, assessing the effect on the organism of any change made in a gene will require systematic screens and tests that allow us to describe the phenotypic consequences in a comprehensive way. EUMORPHIA is an integrated research programme involving the development of new approaches in phenotyping, mutagenesis and informatics leading to improved characterisation of mouse models for the understanding of human physiology and disease. The focus will be on the development, standardisation and dissemination of primary and secondary phenotyping protocols for all body systems in the mouse. The project will also pilot novel approaches to gene-driven mutagenesis and will be supported by new informatics tools within research and networking for the acquisition, dissemination and querying of phenotype data.

What will be the expected benefits for the research field in Europe and for human health?

The programme will provide a platform for the systematic and standardised characterisation of mouse mutant models enabling European researchers and those outside Europe to fully develop the mouse as a tool for characterising gene function, identifying mouse models of human disease and dissecting the underlying genetic basis of disease. The project will bring together leading European mouse geneticists with different and varied expertise in a synergistic manner. Overall, the EUMORPHIA programme will prepare the EU community for the future challenges of the Genomes for Human Health initiative. In the long term, the project has the potential to deliver a major economic impact in the pharma/biotech sector through the generation of novel mouse disease models, the characterisation of novel therapeutic targets and improved tools for advanced, mouse-based, analyses in drug development.

Training and networking aspects: The research programme focuses on dissemination of information through extensive networking involving working groups from EU and abroad bringing expertise to bear in the development and validation of phenotype screens. The training programme will significantly bolster research by bringing new skills from diverse areas such as veterinary and clinical medicine to mouse biology and the study of disease models, while at the same time creating a new cadre of scientists trained in mouse genetics.

The research consortium

Steve Brown
(project coordinator)
MRC Mammalian Genetics Unit, Harwell (UK) s.brown@har.mrc.ac.uk
(Tel : + 44 1235 824541)

Pierre Chambon Inst. Génétique et Biologie Moléculaire et Cellulaire, Strasbourg (FR) Chambon@titus.u-strasbg.fr (Tel: + 33 2 88 65 32 13 15)

Jacques Samarut ANIMAGE, ENS/Genopole Rhone-Alpes, Lyon (FR) Jacques.Samarut@ens-lyon.fr
Mark Lathrop Genoscope, Evry (FR) mark@cng.fr pavner@pasteur.fr
M. Hrabe de Anglis Inst. of Exp. Genetics, Munich (DE) hrabe@gsf.de
R. Balling GBF, Braunschweig (DE) balling@gbf.de
A. Berns Nat. Cancer Institute, Amsterdam (NL) tberns@nki.nl
N. Rosenthal EMBL Mouse Biology Programme, Monterotondo (IT) rosenthal@embl-heidelberg.de
G. Tocchini-Valentini Inst.di Biologia Cellulare, Monterotondo gtocchini@ibc.rm.cnr.it
Urban Lendahl Karolinska Institute, Stockholm (SE) Urban.lendahl@cmb.ki.se
Walter Wahli University of Lausanne (CH) walter.wahli@iba.unil.ch
Denis Duboule University of Geneva (CH) denis.doboule@zoo.unige.ch
Ian Jackson MRC Human Genetics Unit, Edinburgh ian@hgu.mrc.ac.uk
Kay Davies MRC Functional Genetics Unit, Oxford kay.davies@anat.ox.ac.uk
A. Bradley Wellcome Trust Sanger Institute, Cambridge (UK) abradley@sanger.ac.uk
M. Barbacid CNIO, Madrid (ES) barbacid@cnio.es

ANNEXE III

Structural proteomics in Europe (Spine)

Background and objectives of the project: The sequencing of the human genome has been hailed as an epoch making achievement ushering in as yet unbounded opportunities for advances in human healthcare. At a pragmatic level it is generally accepted that such advances can only occur when the genomic information is complemented by advances in our understanding of protein function. A full functional description of a protein nowadays requires knowledge of its 3D structure, but the rate of determination of genomic sequences has far outstripped that of structure determination. The aim of SPINE is to facilitate this process by developing high throughput (HTP) tools for protein over-expression and structure solution. This will involve the introduction of novel robotics techniques into several of the Partner laboratories. SPINE will target the structures of a set of human proteins implicated in disease states, in particular cancer, and neurodegenerative diseases, together with proteins from a set of pathogenic viruses and bacteria, including Herpes viruses and Mycobacter tuberculosis. It is planned that around 30 bacterial and 30 human/viral structures will be determined in the first year, rising to around 300 of each by the end of Year 3.

What will be the expected benefits for the research field in Europe and for human health?

SPINE brings together some of the top European structural biology groups in an unprecedented collaborative effort to develop new methods and technologies driven by the shared scientific focus on a set of targets selected to be of direct relevance to human health and disease. It will act as a model for further activities in this area and will facilitate the development of stronger national activities. Our objectives are:

1) Development of technologies permitting high throughput structure determination by X-ray crystallography and NMR not only of prokaryotic but also of eukaryotic proteins and complexes.

2) Use of these technologies for the determination of the atomic structures of 500+ proteins of medical interest chosen from the following target areas:

bacterial pathogens (e.g. M. tuberculosis, C. jejuni) with a focus on virulence genes and potential drug targets; viral pathogens including a genomic approach to a complex virus (Herpes viridae) and its interacting partners in the host cell, as well as a pan-viral targeting of enzymes proven to be suitable targets for chemotherapy (e.g. replicases and proteases); human proteins or complexes involved in fundamental processes and disease with a focus on protein families relevant to cancer and neuro-degenerative disease (kinases, protease, kinesins, nuclear receptors, cell surface molecules). 3) Establishment of a robust, interactive, dynamic and open network of European centres of excellence, integrating national, international and biotechnological efforts, in which high throughput structure determination is closely integrated with complementary functional and biomedically orientated studies so that it can have a real impact on human health.

Structure based biology will be of paramount importance in pharmaceutics and biotechnology for decades ahead. SPINE will keep Europe at the forefront, industrially as well as scientifically, in a major field founded and largely nurtured in Europe.

Training and networking aspects: The programme will expedite synergistic collaborations between the major nationally funded players, disseminate expertise and provide training for young scientists throughput the EU. Networking in SPINE will have two main components (1) internal networking which aims at communication and reporting both inter- and intra-node (2) external networking which involves firstly dissemination of knowledge generated by the project and secondly outreach to other organisations, academic or industrial, national or international which can contribute to or benefit from the project. One unique feature will be the creation of a WEB-based virtual research centre. The SPINE programme will depend on its success on training a new generation of young researchers and technicians who are familiar with high throughput technologies, are familiar with thinking in genomic terms but at the same time maintain scientific focus and rigour. The project will be recruiting the equivalent of about 170 man-years of effort largely through post-doctoral fellowships and this in itself represents a considerable training programme. In addition intensive work package integration activities will be organised to allow small numbers of scientists from within and outside the network to work intensively and brainstorm on identified problem areas or bottlenecks within or across work-packages. Overall, this initiative will create a reservoir of highly skilled personnel for the pharmaceutical, biotechnology and bioinformatics industries. This will provide the edge that Europe needs to maintain and increase its share in the human health market.

The research consortium

David Stuart
(project coordinator)
MRC, Oxford (UK) Dave@strubi.ox.ac.uk
(Tel : + 44 1865 287546)

Pedro Alzari, Institut Pasteur, Paris (FR) Alzari@pasteur.fr
Ivano Bertini University of Florence (IT) Bertini@cerm.unifi.it
Christian Cambillau AFMB, CNRS, Marseilles (FR) CNRS-mrs.fr" target="_blank"> Chris@afmb.CNRS-mrs.fr
Stephen Cusack EMBL, Grenoble (FR) Cusack@embl-grenoble.fr
Lena Gustafsson Chalmers Univ. of Technology (SE) Lena.Gustafsson@molbiotech.chalmers.se
Rob Kaptein Bijvoet Centre for Biomolecular Research (NL) Kaptein@panda.che.uu.nl
Peter Lindley European Synchrotron Radiation Facility (FR) Lindley@esrf.fr
A. Messerschmidt MPI für Biochemie, Martinsried (DE) Messersc@biochem.mpg.de
Dino Moras CNRS, IGBMC, Strasbourg (FR) Moras@titus.u-strasb.fr
Par Nordlund Stockholm University (SE) Par@dbb.su.se
Titia Sixma National Cancer Inst., Amsterdam (NL) Sixma@nki.nl
Joel Sussmann Weizmann Institute of Science, Israel Joel.sussman@weizmann.ac.il
Janet Thornton European Bioinformatics Institute, Cambridge (UK) Thornton@ebi.ac.uk
Matthias Wilmanns EMBL, Hamburg (DE) Wilmanns@embl-hamburg.de
Keith Wilson University of York (UK) Keith@ysbl.york.ac.uk

ANNEXE IV

Large projects for post-genomic research in the Quality of Life programme - Overview of the selection procedure

To stimulate progress in functional genomics relating to human health in the Fifth Framework programme, the EU Quality of Life Programme (QoL) has recently selected three large integrated projects entitled:

Structural proteomics in Europe. This project aims at developing new technologies and protocols for the determination of new structures at high throughput.

Genome-wide analyses of European twin and population cohorts to identify genes involved in common diseases. This project aims at developing new epidemiology tools and methods to identify genes involved in common diseases by capitalising on very important and unique resources in terms of European population cohorts.

Understanding human molecular physiology and pathology through integrated functional genomics in the mouse model. The main goal of that project is to develop and standardise primary and secondary phenotyping protocols for all mouse body systems.

Due to their scope, size and excellence, these three projects are likely to have a substantial impact in their field and will represent three flagship projects for European research in functional genomics.

Each QoL integrated project contains three components - research, networking, and training & mobility - within a common integrated management structure.

Under the research component, each project proposed research activities "beyond the state of the art" in the corresponding field. The consortia in charge of these three projects bring together the most prestigious laboratories in Europe in the corresponding field. To ensure the critical mass to make a real impact in the field, each project will involve more than 200 researcher-years of effort (Community support of 10-15 M€). In addition, due to their multidisciplinary nature, these projects provide an excellent platform for training. The training and mobility component of the projects offer the possibility to many young researchers to receive a multidisciplinary training in the best European centres. In addition, with the networking component, the projects will have an important European dimension and result in an improved scientific co-ordination of the overall European effort in the corresponding field.

QoL integrated projects were selected by a new two stage procedure that involved, first, a call for expressions of interest for topics from which five topics of strategic importance were selected, followed by a dedicated call for proposals from which the QoL integrated projects themselves were selected. This procedure in two separate steps, mixing both bottom-up (topics proposed by the researchers via the expressions of interest) and top-down (selection of topics of strategic importance) approaches, was designed to select the best QoL integrated projects. In addition, this procedure avoided an excessive over-subscription in the second step, which might have acted as a deterrent to applicants.

An expression of interest consisted of a short document proposing a topic suitable for an integrated project and describing the consortium that would submit a full proposal. The 71 expressions of interest submitted covered a wide range of topics in functional genomics relating to human health. The high-level experts who carried out the selection of topics, were unanimous on the high quality of the expressions of interest. Based on the quality of the science proposed, on the track-record of the members of the proposed consortia and on the strong Community added value, the panel selected 5 topics for the dedicated call for QoL integrated projects. To illustrate the transparency and the efficiency of this selection procedure, a detailed report (signed by all members of the selection panel) on the evaluation of these expressions of interest was published on the following website: http://www.cordis.lu/life/generic/integ _proj.htm .

The five topics published in the dedicated call for QoL integrated projects were:

Development of an integrated platform in bioinformatics and computational biology.

Understanding human molecular physiology and pathology through integrated functional genomics in the mouse model.

High throughput structural genomics related to human health.

Creating and implementing tools for genomic epidemiology of common diseases.

Functional genomics of gender-specific cancers.

In response to the dedicated call, 16 proposals for QoL integrated projects were submitted: 7 proposals in genomic epidemiology, 5 proposals on the mouse model, 2 proposals in structural genomics, 1 proposal in bioinformatics and 1 proposal in cancer.

The Quality of Life Programme made available resources for financing up to three QoL integrated projects. To enlarge the scope of this initiative, the Commission made clear to the applicants that only one proposal could be funded in a given topic.

To guarantee the most efficient and transparent selection of the best QoL integrated projects the Commission established a new evaluation procedure. First of all, in contrast to the regular evaluation procedure for EU RTD proposals, the anonymity rule was not applied for these QoL integrated projects. In the conventional procedure, project proposals are evaluated within Commission premises, offering only a limited access to external sources of information for the evaluator. For the evaluation of QoL integrated projects, the Commission introduced the concept of "external peer review". Each proposal was sent to at least 4 independent (mainly from US or Japan) experts in the corresponding field for a written opinion on the quality of the science, the management and the partnership. Also, a panel of high-level European experts, with complementary expertise in the five selected topics, was established by the Commission to carry out the full evaluation of the proposals. Each panellist received by mail a copy of all proposals 6 weeks prior to the evaluation meeting, held on 13-14/12/2001 in Brussels. Three weeks prior to this evaluation meeting, the written opinions of the reviewers were sent to the panellists. The evaluation meeting in Brussels involved an interview with the co-ordinator of every proposal. This interview, another new aspect of this evaluation procedure, provided the co-ordinators with an opportunity to clarify aspects of their proposals. In a consensus decision, the panellists produced a ranking list of proposals, taking into account their own assessment of the proposals, the written opinions of the reviewers, and the interviews.

The new instruments (networks of excellence and integrated projects) foreseen for the 6th Framework Programme have the same objectives as the QoL integrated projects: excellence, multidisciplinarity, networking and training. Therefore, this new evaluation procedure for the selection of the QoL integrated project will certainly benefit the preparation and implementation of future FP6 networks of excellence and integrated projects.

For a better view of the tabular information

Source: Research DG http://europa.eu.int/comm/dgs/research/ index_en.html