Bruxelles, 18 mars 2002

Mots-clés: : ADN, santé humaine, génome, protéomique

Dans une volonté de donner à la recherche en génomique une nouvelle dimension à travers l'étude des gènes et de leur fonction, la Commission européenne a accordé €39,4 millions à trois projets grands projets de recherche. Ce financement est le prélude aux €2.2 milliards prévus dans la nouvelle action clé "recherche en génomique pour la santé humaine" dans le prochain programme de recherche communautaire qui sera lancé à la fin de cette année. Les projets sur la génétique des jumeaux, la génomique chez la souris et la protéomique structurale préfigurent la nouvelle approche de la Commission au financement de la recherche pour l'avenir : en demandant aux scientifiques des sphères industrielle et académique de constituer des équipes de très haut niveau en Europe, afin de conduire la recherche aux frontières de la science dans un nombre sélectionné de domaines tout en leur donnant les moyens nécessaires pour atteindre une masse critique et une excellence de niveau mondial.

Cet effort s'inscrit dans la volonté de la Commission Européenne d'investir plus et mieux dans la création du savoir et de construire un Espace Européen de la Recherche et de l'Innovation cohérent, comme l'ont demandé les chefs d'état et de gouvernement réunis au sommet de Barcelone.

Pour le Commissaire à la Recherche Philippe Busquin "Le décodage du génome humain crée de nouvelles opportunités pour les chercheurs de comprendre les origines génétiques des maladies et de développer de nouvelles thérapies. Il est vital pour l'Europe de jouer un rôle majeur dans la recherche génomique et la biotechnologie, la nouvelle frontière du 21ème siècle. Mais nous ne pourrons exploiter ce vaste potentiel, pour améliorer la qualité de la vie et la compétitivité de l'Europe, que si nous sommes capables de mieux nous organiser pour relever des défis qui sont au-delà de la seule portée des pays."

Les trois projets financés par la Commission Européenne sont les suivants :

Etudes sur des jumeaux européens volontaires pour identifier les gènes impliqués dans des maladies communes, coordonné par le Prof. Leena Peltonen, Helsinki, Finlande.
Etant donné l'identité de leur patrimoine génétique, les vrais jumeaux constituent un groupe d'un grand intérêt pour les chercheurs en biomédecine pour identifier le potentiel génétique des origines de maladies communes. Si l'on observe que des jumeaux développent tous deux la même maladie au cours de leur vie, il y a fort à croire qu'il existe une base génétique à cette maladie. Cette information couplée à la connaissance de la séquence génomique permettra aux chercheurs d'associer des facteurs génétiques à des maladies. L'identification et la compréhension de ces gènes ouvrent la voie au développement de nouveaux outils diagnostiques et de nouvelles thérapies. En mettant en réseaux les principaux "registres de jumeaux" en Europe et les meilleurs chercheurs dans ce domaine, ce projet européen augmentera de façon considérable les chances d'identifier les origines génétiques de maladies communes telles que les maladies cardio-vasculaires. Une contribution de l'union européenne de €13,4 millions sur 4 ans est prévue (voir annexe 1 pour plus d'information).

La compréhension des maladies humaines à travers la génomique de la souris, coordonné par le Prof. Steve Brown, Harwell, R-U. et le Prof. Pierre Chambon, Strasbourg, France.
Le génome de la souris est à 95% identique au génome humain. Par conséquent, les souris souffrant de maladies génétiques sont potentiellement de très bons modèles pour les maladies équivalentes chez l'homme. Ces modèles sont essentiels pour développer et tester de nouvelles thérapies candidates pour traiter des maladies humaines. En Europe, les chercheurs ont isolé des souris développant des maladies semblables à celles observées chez l'homme. Néanmoins, afin de confirmer ces similarités entre les maladies murine et humaines, un effort considérable est nécessaire pour réaliser une analyse profonde de chaque souche de souris. Ce projet vise à analyser en détail le grand nombre de souris mutantes déjà disponibles, afin que les meilleurs modèles murins pour chaques maladies humaines soient identifiées de manière efficace. Une autre conséquence de cette coopération européenne sera la réduction du nombre d'animaux utilisés pour la recherche. Une contribution de l'union européenne de €12,3 millions sur 3 ans est prévue (voir annexe 2 pour plus d'information).

Protéomique structurale en Europe, coordonné par le Prof. David Stuart, Oxford, R-U et le Prof. Dino Moras, Strasbourg, France.
Les gènes codent des protéines et ce sont ces protéines qui effectuent tous les processus biologiques de la vie. La connaissance de la structure tri-dimensionnelle d'une protéine est essentielle pour prédire ses fonctions. L'analyse structure-fonction de protéines normales et de protéines liées à des maladies est également de première importance pour l'industrie pharmaceutique développant de nouveaux médicaments. Cependant, la détermination de la structure d'une protéine est un processus long et coûteux nécessitant des infrastructures et des équipements majeurs et des connaissances très pointues. Ce projet européen permettra d'accélérer ce processus en optimisant chaque étape pour le haut débit, tel que la production, purification, cristallisation des protéines et l'analyse des structures. Les structures de plus de 600 protéines d'intérêt médical seront identifiées. Une contribution de l'union européenne de €13,7 millions sur 3 ans est prévue (voir annexe 3 pour plus d'information).

Par leur taille, leur envergure et le très haut niveau des équipes de recherche impliquées, ces projets mèneront à des avancées substantielles dans la compréhension des liens entre génome humain et maladies, renforceront la position de l'Europe dans ce domaine de recherche important et apporteront à terme des bénéfices aux patients. De plus, les nouvelles caractéristiques de ces projets, leur nature intégrée et leur dimension, font d'eux d'utiles précurseurs à deux des "nouveaux" instruments proposés dans le Sixième Programme Cadre (2002-2006), notamment les projets intégrés ainsi que les réseaux d'excellence. La procédure originale employée pour susciter, évaluer et sélectionner ces projets est décrite dans l'annexe 4.

· Pour des informations complémentaires sur ces projets, veuillez contacter :

• Jacques Remacle, Responsable Scientifique, Programme Qualité de la Vie, DG Recherche
  Tél. : +32.2.296.30.45
  E-mail : jacques.remacle@ec.europa.eu
• Bernard Mulligan, Responsable Scientifique, Programme Qualité de la Vie, DG Recherche
  Tél. : +32.2.296.81.72
  E-mail : bernard.mulligan@ec.europa.eu

Pour plus d'information concernant la presse, veuillez contacter:

• Stéphane Hogan, Responsable Relations Presse, DG Recherche
  Tél. : +32.2.296.2965 - Fax: +32.2.295.8220
  E-mail : Research Contact
  

(Toutes les annexes sont en anglais)

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

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

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

The research consortium

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://cordis.europa.eu/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.