Foreword
 Genomic approaches play a key role in the Life Sciences today, in the search for basic knowledge, which builds the foundations of systems biology, and in the more applied fields of human health and disease. Our aim at the European Commission is to stimulate and sustain multidisciplinary basic research to exploit the full potential of genome information. That's why genomics is present through the whole Sixth Framework Programme in all Life Sciences programmes (health, food, environment), and in particular in the Fundamental Genomics workprogramme, which funds the research highlighted in this newsletter. We are proud of the European scientists who collaborate in top-class research projects in fields such as gene expression, proteomics, bioinformatics, structural genomics, comparative genomics, population genetics or basic biological processes. Some of their dreams and achievements will have a place in these pages.
Octavi Quintana i Trias Director of Health at DG Research
European Commission
Genome research supported by the European Framework Programme - Manuel Hallen
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Dr Manuel Hallen is the Head of Unit F4 “Fundamental Genomics” at the Directorate-General for Research in the European Commission. |
Throughout history, Europe has been a crucible for developing new ideas. Genome research, alongside proven conventional approaches, is a good example of this. It is opening up new fields of knowledge and unprecedented opportunities to improve human health and stimulate industrial and economic activity. Post-genomic research will then lead to many applications in a number of health-related sectors, notably in the development of new diagnostic tools and treatments to combat major diseases.
The rationale for coordinating the activities related to genome research at the European level is based on its potential contribution to the understanding of the processes underlying human disease, hence to improve diagnostics, treatment and eventually disease prevention. The Member States of the European Union (EU) are confronted with a number of pressing health problems, some of which, because of their size and nature, demand that research be carried out at the EU rather than at the national level. This research will often require up- stream collaborative fundamental research since it is inappropriate to try and apply what one does not understand. In addition, it is essential to recognise that tackling practical problems through scientific research has been, and continues to be, a powerful driver of socio-economic growth and a stimulus to science.
Research in Europe is supported by different mechanisms of funding, from the regional to the national and European transnational levels. The European Union funds research through the successive Framework Programmes which have played a cohesive role in addressing the fragmentation of the genome research community in Europe by funding collaborative research projects and transnational access to infrastructures.
In a drive to gear up research on functional genomics – the study of genes and their function – in 2001 the European Commission launched a pilot experiment as a prelude to the €2 255 million earmarked for this field of research in the Sixth Framework Programme (2002-2006). As a result €39.4 million have been awarded to three large research projects[1] in genomics research for human health in order to demonstrate the new way in which the Commission will fund research in the Sixth Framework Programme by asking scientists 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. The three pilot projects (GenomEUtwin, EUMORPHIA, SPINE) have been running since October 2002 and their experiences and first results are detailed in different articles in this newsletter.
Through their size and scope and the world-class research teams involved, this new type of project 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.
The new features of this type of project, their integrated nature and size make them useful precursors to two of the 'new' funding instruments, notably the Integrated Projects and the Networks of Excellence that are now being used to fund research in the Sixth Framework Programme.
Fundamental genomics research into health and disease is one of the main action lines in the Life Sciences programme. The strategic objective of this line is to foster the basic understanding of genomic information by developing the knowledge base, tools and resources needed to decipher the function of genes and gene products relevant to human health, and to explore their interactions with each other and with their environment. Specific research areas address: Gene expression and proteomics, Structural genomics, Comparative genomics and population genetics, Bioinformatics, and Multidisciplinary functional genomics approaches to basic biological processes.
This electronic newsletter aims to take a proactive role by informing European scientists about most recent EU research activities in the field, with particular emphasis on collaborative fundamental research into genomics.
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[1] Studies of European volunteer twins to identify genes involved in common diseases – 'GenomEUtwin', www.genomeutwin.org; Understanding human disease through mouse genomics – 'EUMORPHIA', www.eumorphia.org; Structural proteomics in Europe – 'SPINE', www.spineurope.org
Temblor – a shared opportunity
Temblor is a three-year project designed to build up and improve access to the European resource in bioinformatics. Coordinated by the European Bioinformatics Institute (part of the Molecular Biology Laboratory), it comprises four linked projects involving 25 collaborators in 12 countries, funded together as a ‘cluster’.
Bioinformatics has become an essential tool for genomics research. With full sequencing of the human genome, and of other organisms vital to medical research, now completed, researchers are faced with an enormous overload of data. Although the human genome probably contains only about 30 000 genes but these generate hundreds of thousands of proteins, each one with a specific functions in the body. Bioinformaticians have developed many different databases to catalogue genes, their products, and the functions of those products, but if researchers are to make the most of the wealth of available data they must be able to ask questions across these databases, which is a complex task.
The backbone of Temblor, a project called Intgr8, aims to give database users a much simpler way of accessing and linking the different sources of genomic and proteomic data by providing a single access point via an integrative layer which uses individual genes as the starting point. The project is developing new tools to exploit this layer using new algorithms and text-, structure- and sequence-based services, will provide researchers with new ways to explore in their genomic context.
Integr8 will draw on databases maintained at major European bioinformatics centres, and on important new resources funded through Temblor. These new resources are summarised below.
Standardising procedures
Defining how proteins interact with each other is an important step towards understanding how individual gene products form pathways, networks and entire systems. The IntAct project is defining standards for the collection of protein-protein interaction data. A new database brings together the large sets of data already available, cross-validates them and provides innovative and user-friendly visualization tools.
The European Macromolecular Structure Database project aims to provide biologists with standardised ways of viewing and describing 3-D macromolecular structures, particularly protein families, so that they can search, analyse and share structural data more effectively. 3-D structures give important insights into how macromolecules function in the body.
The number of hybridizations (individual experiments) in ArrayExpress has been growing rapidly since its launch in February 2002, reflecting its popularity as a means of sharing microarray based gene expression information. Data courtesy of Alvis Brazma, EMBL-European Bioinformatics Institute, Hinxton, UK.
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DNA microarray technology helps researchers understand which genes are active in specific cells under different conditions. They allow data on many thousands of genes to be collected simultaneously, but for this data to be described, exchanged, stored and analysed effectively, standardised procedures need to be developed. The DESPRAD project has developed a public repository for microarray data that conforms to agreed community standards. The Database, known as ArrayExpress and is now being rapidly populated with data.
http://www.ebi.ac.uk/Information/funding/temblor.html
Project coordinator:
Graham Cameron
EMBL Outstation - the European Bioinformatics Institute, UK
cameron@ebi.ac.uk
Eumorphia – of mice and men
Eumorphia is a three-year project involving 17 major mouse genetics laboratories across the European Union. It aims to develop new approaches to improving the classification of mouse models used to understand human disease, leading to standardised screening processes for the identification of different mouse mutants. These will be made freely available to scientists worldwide, thereby providing an essential research tool for the development of genomic research.
The project was launched at the end of 2002, just two months before publication of the draft sequence of the mouse genome. This sequence confirmed that mice have a similar number of genes to humans (around 30 000) and share 99% of their genome. The mouse has been the main mammalian model used in research since the 1980s because of the ease and accuracy with which it can be genetically modified by a variety of mutagenesis approaches to produce models of human disease, and to test drug and gene therapies.
To determine the function of each mouse gene – and hence its equivalent human gene – the effect of manipulating the gene must be carefully screened to give an accurate description of the phenotypic consequences. However, many labs use their own particular research protocols for screening mice, making it difficult to accurately compare and share data from different sources. Even variations in how mice are handled or the type of equipment used can result in important differences between labs screening the same mouse mutant. If identification of the function of all 30 000 human genes is to progress rapidly, collaboration is of paramount importance.
Screen tests
Over the past 18 months, the Eumorphia project has enabled the exchange of information and screening protocols for primary screens – those applicable to all mouse mutants – between participating institutes. After testing, optimisation and validation, a large number of primary screen ‘Standard Operating Procedures’ (SOPs) have now been written and will be available on the Eumorphia website by the end of June 2004. These will form part of the European Comprehensive First Line Phenotyping Protocol (ECFLP) and will ensure that results coming from labs adhering to the protocol are comparable. Secondary and tertiary screens, relevant to specific mutants, are being developed and will be put on the website when completed.
A crucial element of Eumorphia is the development of a powerful – yet user-friendly – database underpinning the SOPs. Bioinformatics specialists are developing standardised formats for describing different phenotypic traits and analysing results. These standardised descriptions, known as ontologies, are now being taken up by the international mouse genomics community which is convinced of the importance of such EU collaboration.
http://www.eumorphia.org/
Project coordinator:
Professor Steve Brown
MRC Mammalian Genetics Unit,
Medical Research Council, Harwell, UK
s.brown@har.mrc.ac.uk
Eumorphia – of mice and men
Eumorphia is a three-year project involving 17 major mouse genetics laboratories across the European Union. It aims to develop new approaches to improving the classification of mouse models used to understand human disease, leading to standardised screening processes for the identification of different mouse mutants. These will be made freely available to scientists worldwide, thereby providing an essential research tool for the development of genomic research.
The project was launched at the end of 2002, just two months before publication of the draft sequence of the mouse genome. This sequence confirmed that mice have a similar number of genes to humans (around 30 000) and share 99% of their genome. The mouse has been the main mammalian model used in research since the 1980s because of the ease and accuracy with which it can be genetically modified by a variety of mutagenesis approaches to produce models of human disease, and to test drug and gene therapies.
To determine the function of each mouse gene – and hence its equivalent human gene – the effect of manipulating the gene must be carefully screened to give an accurate description of the phenotypic consequences. However, many labs use their own particular research protocols for screening mice, making it difficult to accurately compare and share data from different sources. Even variations in how mice are handled or the type of equipment used can result in important differences between labs screening the same mouse mutant. If identification of the function of all 30 000 human genes is to progress rapidly, collaboration is of paramount importance.
Screen tests
Over the past 18 months, the Eumorphia project has enabled the exchange of information and screening protocols for primary screens – those applicable to all mouse mutants – between participating institutes. After testing, optimisation and validation, a large number of primary screen ‘Standard Operating Procedures’ (SOPs) have now been written and will be available on the Eumorphia website by the end of June 2004. These will form part of the European Comprehensive First Line Phenotyping Protocol (ECFLP) and will ensure that results coming from labs adhering to the protocol are comparable. Secondary and tertiary screens, relevant to specific mutants, are being developed and will be put on the website when completed.
A crucial element of Eumorphia is the development of a powerful – yet user-friendly – database underpinning the SOPs. Bioinformatics specialists are developing standardised formats for describing different phenotypic traits and analysing results. These standardised descriptions, known as ontologies, are now being taken up by the international mouse genomics community which is convinced of the importance of such EU collaboration.
http://www.eumorphia.org/
Project coordinator:
Professor Steve Brown
MRC Mammalian Genetics Unit,
Medical Research Council, Harwell, UK
s.brown@har.mrc.ac.uk
SPINE – strengthening structural biology
The SPINE project aims to speed up the structural determination of proteins important for human health through the development of high-throughput technologies. Linking protein structure to function is an essential step in the identification of potential targets for new drugs and understanding disease processes. The project has already made a vital contribution to the structure determination of a protein from the SARS (Severe Acute Respiratory Syndrome) coronavirus[1, 2]
SARS coronavirus nsp9 replicase protein
SPINE’s targets are proteins from bacterial pathogens, such as Mycobacter tuberculosis, viral pathogens such as Herpesviridae, and human protein families, particularly those relevant to cancer and neuro-degenerative diseases. Selected proteins are targeted for their roles in pathogenic virulence or because they are potential drug targets. The pharmaceutical and biotechnology industries are closely involved in this project to ensure that results are quickly transferable and have a real impact on human health.
Pooling resources
Determining protein structure is a lengthy and costly process requiring large-scale equipment for X-ray crystallography and nuclear magnetic resonance, complex infrastructure, and multidisciplinary expertise. The SPINE project is harnessing European expertise and resources in structural biology – 20 partners in seven countries – to achieve what no single partner can do alone. Each step of the structure determination process, from target selection, to protein production, purification, crystallisation and structure analysis, is being optimised to increase throughput. For example, the crystallisation stage, a vital precursor to X-ray analysis of the protein’s 3D structure, is being automated by the use of extreme precision robotics.
A key partner in the project is the European Bioinformatics Institute, bringing expertise in software-based target selection. The EBI also tracks and disseminates the status of SPINE targets to ensure that results are distributed rapidly and efficiently worldwide.
The combination of bioinformatics and knowledge gained from high-throughput technologies makes suitable target proteins easier to select – the ‘low-hanging fruit’ approach. This new collaborative approach means that researchers can react quickly to urgent scientific challenges. The SARS protein structure – a protein which plays a key role in replication of the virus – was solved just six months after the virus was identified.
http://www.spineurope.org
Project coordinator:
Professor David Stuart
Division of Structural Biology
Oxford University, UK
dave@strubi.ox.ac.uk
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[1] Structure (12) 341, February 2004
[2] Proceedings of the National Academy of Sciences (11), 16 March 2004
GenomEUtwin – doubling the impact
The GenomEUtwin project aims to harness the unique features of twins for large-scale studies of the environmental and genetic factors underlying complex diseases. By networking current research in population genetics using studies of twins across Europe and beyond, the project is providing powerful new statistical tools and compatible research approaches to ensure more rapid progress in identifying the links between genetic profile and disease susceptibility.
Common diseases such as diabetes, coronary heart disease, and stroke are considered to be ‘complex’ because of the large number of factors – genetic, environmental and lifestyle – influencing their development. Overall, they create a massive drain on European healthcare services.
Registering the data
Twins, with an identical genetic make-up, represent an invaluable resource for the study of complex diseases. If both twins develop the same disease during their lifetime there is a high probability that a genetic basis for the disease will be confirmed. A number of twin registries have been developed across Europe, containing samples of DNA from volunteers, coupled with data on their medical history across their lifespan. However, because of the multifactorial nature of complex diseases, studies of their epidemiology require data from very large numbers of people to ensure that the results are statistically significant. By networking Europe’s twin registries, the GenomEUtwin project is not only providing this critical mass of data, involving 850 000 twins, but is also harmonising the way samples are collected and analysed to ensure that data is comparable between the registries, and that similar procedures for informed consent and data protection are respected. With the recent addition to the project of the Australian twin registry, the network now involves eight registries from Finland, Sweden, Norway, Denmark, Netherlands, Italy, UK and Australia, with other links being developed with the Estonian Genome Programme and the Canadian CARTaGENE population study.
Genetic data from the twin registries is also being compared to data from the Morgam project, a multinational collaborative study exploring the relationships between the development of cardiovascular diseases and their classic and genetic risk factors in 160 000 volunteers from a cross-section of the population. This will give researchers the chance to see if findings from the twin registries also hold true for the wider population.
GenomEUtwin represents a unique collaboration between top researchers in genetics, epidemiology, bioinformatics, and ethics and is providing a powerful resource for European genomics research. Training opportunities offered by GenomEUtwin are advertised on the project website.
http://www.genomeutwin.helsinki.fi/
Project coordinator:
Professor Leena Peltonen,
National Public Health Institute, Helsinki Biomedicum, Finland
info@genomeutwin.org
Quality proposals boost project funding
Following the first call for proposals under the Sixth Framework Programme’s ‘Life Sciences, Genomics and Biotechnology for Health’ thematic priority (25 March 2003), 32 projects were selected in the field of fundamental genomics. These projects build upon the excellence of the strong fundamental genomics community which already exists in Europe in both public and private sectors. They will provide the critical mass necessary for the European Union to remain competitive in this fast-moving field which holds so much promise for human health.
The high quality of proposals submitted led the Commission to increase the budget available for fundamental genomics from €134 million to €166 million. Of this, 80% will fund the so-called ‘new instruments’ in FP6 – Integrated Projects (IP) and Networks of Excellence (NoE) – which aim to structure and give critical mass to research across the EU. Some of the selected projects are direct ‘descendants’ of FP5’s pilot Integrated Projects (see below). The remaining budget will fund the more traditional smaller projects (Specific Targeted Research Projects) and other auxiliary projects (Specific Support Actions).
The 32 projects were selected from 116 proposals after a rigorous evaluation procedure involving experts from academia, public and private research organisations and industry. Five key areas in fundamental genomics are covered by the selection:
- Gene expression and proteomics
The projects funded here will lead to a better understanding of the function of genes and their products, using advanced microarray technologies, and of protein-protein interactions, using high-throughput proteomic technologies. This knowledge will speed up the identification of genetic variation in DNA, which underlies disease, and will shed light on how such variation affects vital cell functions.
- Structural genomics
Determination of the 3D-structure of macromolecules such as proteins is critical to understanding their role in complex biological processes. It is also vital for the identification of appropriate targets for new medicines. Selected projects will develop new technologies and high-throughput research methodology in 3D electron microscopy (in one NoE), X-ray crystallography, and synchrotron radiation to speed up protein structure determination and overcome current bottlenecks.
- Comparative genomics and population genetics
The projects funded will enable scientists to use well-characterised model organisms, such as zebra fish and the nematode C. elegans, for predicting and testing gene functions and their link with human development and disease. Technologies for improved in vivo imaging of molecular function in cells and model animals will also be developed.
- Bioinformatics
This study area is a vital resource for genomics researchers, enabling them to make sense of the massive amounts of genome data now available. One NoE will structure the EU effort to annotate genome data and establish a European School of Bioinformatics to encourage essential training in the field. Other projects will develop computer-based prediction of gene function and simulation of complex regulatory networks, making an important contribution to the development of new drugs, diagnostics and therapies.
- Multidisciplinary functional genomics approaches to basic biological processes
Projects funded under this heading aim to help researchers understand the mechanisms underlying fundamental biological processes relevant to human health, using the different functional genomics disciplines described above. Selected projects include studies of mitosis, cell signalling, the lymphatic system, wound healing, stem cell differentiation, bacteria as targets for, and sources of biopharmaceuticals, and the role of non-coding RNA in disease. In addition, NoEs in epigenetics – the study of the biological mechanisms that regulate gene expression, and in chronic inflammation – a major clinical problem, will ensure that European excellence and resources in these fields are well coordinated.
First call:
http://fp6.cordis.lu/fp6/call_details.cfm?CALL_ID=4
List of selected projects: http://ec.europa.eu/research/fp6/p1/firstcallresult_en.html
MOLTOOLS – Europeans join forces to develop better biochips
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Source: Jonas Jarvius - Uppsala University |
A new Integrated Project has been launched in the area of high-throughput microarray technology. This project addresses the next big challenge in molecular technology development - the requirement for analyses of individual genomes and proteomes.
Lasting for 3 years, the project will develop a next-generation toolbox, which should allow for the analysis of the genome, transcriptome and proteome of individuals.
The project brings together leading European groups in the area of molecular biological technology development, having pioneered a series of important molecular techniques to enable a new generation of array-based molecular and cellular processes to access extensive biological information.
The project is coordinated by the University of Uppsala in Sweden. For further information please visit the project’s website: www.moltools.org
FunGenES - A European partnership to advance stem cell research
This new three-year IntegratedProject will focus exclusively on mouse embryonic stem cells. It aims to improve the understanding of how the information contained in the sequence of a mammalian genome directs development from a single-celled fertilised oocyte to a complex adult organism.
FunGenES will map the gene subsets used in i) pluripotent, ii) lineage-committed multipotent, and iii) selected differentiated cell types to make an atlas of mammalian genome utilisation in early development.
The FunGenES consortium consists of 18 industry and research organisations from Germany, France, Italy, Portugal, Greece and the UK. The scientific coordinator is Prof Dr Jürgen Hescheler, University of Cologne, from whom more details can be obtained.
Email: J.Hescheler@uni-koeln.de
The kick-off meeting for the Integrated project MITOCHECK is being organised on the 13-14 May 2004 in Vienna.
This project is focusing on the regulation of mitosis by phosphorylation, using a combined functional genomics, proteomics and chemical biology approach.
The project coordinator is Dr Jan-Michael Peters (peters@imp.univie.ac.at) at the Research Institute of Molecular Pathology (IMP-Vienna), sponsored largely by the pharmaceutical company Boehringer Ingelheim in Vienna.
INTERACTION PROTEOME, the largest EU-funded project in the field of proteomics to date started on 1 January 2004.
This Integrated Project brings together the scientific excellence of eleven leading European research institutions and companies, including the largest European manufacturers of mass spectrometers and electron microscopes. The broadly applicable platform of routine methods for the analysis of protein interaction networks will provide the basis for an efficient analysis and systems modelling of fundamental biological processes in health and disease. For further information, please contact Dr Anne Katrin Werenskiold (Project Manager), Max Planck Institute of Biochemistry, Martinsried/Germany.
E-mail: kwerensk@biochem.mpg.de
BIOXHIT workshop on Automated X-ray Provision
3-4 May 2004 at ESRF, Grenoble, France
This workshop is organised in the context of the Integrated Project BIOXHIT (Biocrystallography (X) on a Highly Integrated Technology
Platform for European Structural Genomics), Section 2 'Synchrotron technologies'. It aims at sharing information and creating collaborations in order to develop integrated software that can be shared in general by synchrotron radiation facilities and in particular by BioXHIT participants.
The main emphasis of the workshop will be software technologies for automatically aligning, monitoring and maintaining the X-ray beam up to the sample position.
Workshop sessions
1. Beamline Control Module
2. Automation of Delivery of X-rays - Automatic Beamline Alignment
3. Data Management - Historical Databases
The workshop will consist of approximately 15 presentations; a large amount of time will be reserved for discussions.
For more information please visit the project's website: www.bioxhit.org
Preliminary Announcement of a conference:
'Exploring complementary strategies for funding of basic research in the life sciences in Europe.'
Brussels, 13 December 2004 (n.b.: new date)
The European Commission's Research Directorate-General will organise a conference that aims to bring together key European stakeholders to establish a forum that will define complementary strategies for better coordination of funding of basic research in the life sciences in Europe.
In the 'post-genomic era', the characteristics and needs of basic research in the life sciences are changing dramatically: it has become very multidisciplinary, the amount of data is increasing exponentially, and huge investments in facilities are required. Collaborative research and 'single lab' research are equally important in the successful pursuit of basic research in the life sciences. Basic research in the life sciences is supported by many national or European funding agencies, so far with only limited attempts at coordination, which has led to substantial fragmentation, duplication of effort, and missed scientific opportunities which should be addressed.
Attendance is by invitation only. A conference website will be available shortly. For further information, please contact Henriette van Eijl or Jacques
Remacle, European Commission, by e-mail.
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Open Call for the NET Programme
A consortium of 25 European scientists has successfully applied for the establishment of a Network of Excellence (NoE) in epigenetic research within the 6th Framework Programme (FP6). This NoE will integrate 8 newly established teams (NET) by competitive call in 2004. Integration will include full access to all NoE activities and a 3-year research grant of €150 000.
Applicants should preferably be within their first 5 years of independent research, hold a position in an institute eligible for funding via FP6 and be willing to contribute towards the joint programme of activities.
Deadline for applications: 16 May 2004.
For information on the NoE and how to apply, please visit: http://www.epigenome.imp.ac.at
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