Epigenetic plasticity of the genome
The Epigenome Network of Excellence (NoE) was created with the long-term aim to build a strong base for scientific excellence in the field of the European epigenetic research in the post-genomic era.
Now after five years, the NoE includes an original core of 25 members plus 35 associate members and 23 Newly Established Teams (NETs): a total of 83 laboratories from 12 European countries. Through the success of the NET programme, young European investigators in their first four years of independent research have been integrated by giving a powerful impetus to a cohort of young research talent.
The NoE programme of activities has promoted a common identity and generated numerous collaborations through training and mobility programmes, workshops, meetings and dissemination of technologies. In 2007 alone, the NoE collectively published some 300 research articles. A major effort has also been made to reach out to the broader community and to the general public. In this "post-genomic" era, advances in epigenetic research represent a new frontier that is predicted to yield novel insights into gene regulation, cell differentiation, stem cell plasticity, development, human diseases, cancer, infertility and ageing.
Advances in hearing science: from functional genomics to therapies
The Eurohear project, comprised of 25 research teams, is building on their work on genetic and molecular mechanisms underlying hearing impairment. EuroHear aims to identify the molecules that play a critical role in the inner ear, and more specifically in the cochlea or the auditory sensory organ.
The project has three closely related objectives: 1) To identify the genes underlying sensorineural hearing impairment, in turn enabling research on these molecular mechanisms involved in the development and functioning of the inner ear; 2) to understand the mechanisms underlying normal and impaired hearing and 3) to develop tools for preventing and treating hearing impairment.
The identification of human hearing genes is made possible by the active involvement of hearing-impaired patients and their families and the use of mouse models for deafness. During the first three years the consortium has made significant advances and already identified and characterized 13 novel human genes required for hearing. A major goal in the future is to identify the molecular basis of hearing loss in the elderly. The consortium has ascertained for this goal a large patient collection and identified the first susceptibility loci by genome-wide studies in patient cohorts which are currently being studied by genetic and functional follow-up studies.
Entrainment of the Circadian Clock
EUCLOCK is a European-wide research consortium involving scientists from 28 institutions (11 countries). Its main aim is to investigate the circadian clock in the context of entrainment and in different organisms, from cells to humans. The project aims to understand, for example, the misalignment between internal and external time, as a consequence of shift-work, as well as insufficient entrainment owing to age-related changes, both elements which can have a strong impact on health and well-being. A major objective of EUCLOCK is to enable large-scale, non-invasive studies (the CLOCK-watcher device) that can prove or disprove the efficacy of medical treatment of pathologies, ranging from heart diseases to cancer, using 24-hour monitoring of impact of these treatments.
New genetic components that control the circadian clock and its entrainment have been identified so far, both in animals and humans. These findings will enable the field of chronobiology to exploit the advantages of systems' biology research on circadian timing, and to perform and integrate the findings at the level of the genome, the proteome, and the metabolome.
Integrated functional genomics in mutant mouse models as tools to investigate the complexity of human immunological disease
The MUGEN network of excellence brings together 19 top immunology research groups and 5 SMEs from 9 EU countries (plus 1 from the US). It is dedicated to bridge the gaps in immunological research by assembling, coordinating and exploiting the animal model resources of the participants and to employ a unifying functional genomics approach to efficiently predict and finally validate dominant gene function with pathogenic relevance for human immunological disease. The objectives are divided into activities related to research, integration and spreading of excellence.
Research activities are organized into four topics. Topic1 will use functional genomics in animal models to analyze basic immunological processes. This includes the study of the innate immune response, pro-inflammatory networks, antigen recognition, acquired immune modulation, tolerance, and intracellular signaling cascades. Topic 2 is concentrated on functional genomics in animal models to study human immunological diseases. These include infectious disease models (viral and microbial), Rheumatoid arthritis, inflammatory bowel disease, Type I diabetes, CNS autoimmune disease (multiple sclerosis) and modulation of cancer. These studies utilize the most state-of-the-art conditional and inducible mutant/cancer mice. Topic 3 uses animal models to identify immune disease susceptibility genes. Comparative genetic linkage analysis will be performed on mouse models and the creation of new mutant mice will be initiated. Random mutagenesis will be performed on disease sensitized existing mouse models. Topic 4 involves animal models for drug development and validation. These experimental platforms will incorporate the SMEs for large scale mouse model testing. For further applicability to human immune responses, the humanized SCID model will be used. The animal models will provide the basis for expression analyses to reveal genetic networks in normal immune function and disease. Data comparisons and bioinformatics will be performed in an integrated manner in the bioinformatics platform for the maximization of data dissemination, induction of intellectual creativity and scientific insight based on integrated data and management of complex knowledge.
A European Network for Integrated Genome Annotation
The objective of the BIOSAPIENS Network of Excellence is to provide a large-scale, concerted effort to annotate genome data by laboratories distributed around Europe, using both informatics tools and input from experimentalists. The Network has created a European Virtual Institute for Genome Annotation, bringing together many of the best laboratories in Europe. The institute will help to improve bioinformatics research in Europe, by providing a focus for annotation and by the organisation of European meetings and workshops to encourage cooperation, rather than duplication of effort.
An important aspect of the network activities is to try and achieve closer integration between experimentalists and bioinformaticians, through a directed programme of genome analysis, focused on specific biological problems. The annotations generated by the Institute will be available in the public domain and easily accessible on the web. This will be achieved initially through a distributed annotation system (DAS), which will evolve to take advantage of new developments in the GRID.
The Institute has established a permanent European School of Bioinformatics, to train bioinformaticians and to encourage best practise in the exploitation of genome annotation data for biologists. The courses and meetings will be open to all scientists throughout Europe, and available at all levels, from basic courses for experimentalists to more advanced training for experts.
The basic European School of Bioinformatics courses will be held twice a year, in a different country every time, and will be followed, in the same location, by a workshop on one of the topics of interest of the network. It will consist of a six days entry level for inexperienced users and newcomers to the field.
European scientists have traditionally been very active in the field of protein and genome annotation, and Ensembl and SWISS-PROT (now part of UniProt) are the primary resources in use worldwide. Many of the tools used in genome and protein sequence and structure annotation, prediction and validation, and pathway analysis have been developed in Europe. The BioSapiens NoE will further increase European competitiveness, by new discoveries, increased integration, expert training and improved tools and services, and enhance Europe's role in the academic and industrial exploitation of genomics.
Molecular intervention strategies targeting latent and lytic herpesvirus infections
Herpesviruses cause many human diseases varying from afflictions of moderate severity to serious infections that are life-threatening. At present the options for therapy are limited, and, because of toxicity, the current antiherpes drugs cannot be administered to pregnant women. There is a continuing need for alternative treatment strategies also because drug-resistant viruses are evolving.
The goal of the TargetHerpes project is the development of novel antiviral compounds (such as peptides or siRNAs) that can be further developed into antiviral drugs. The candidate compounds are identified and tested in cell culture systems and then applied in small animal models. The project targets different herpesviruses at different stages of their infections in order to inhibit virus entry, evasion of host defences, persistence in infected individuals and reactivation from latency. Some promising anti-herpesvirus inhibitors have already been identified based on the use of siRNAs and peptidomimetics in in vitro assays.
The TargetHerpes is composed of 9 partners, including 3 SMEs that provide technological platforms enabling the whole consortium to achieve the project goals.
Opticryst (STREP dedicated to SME: 7 SMEs out of 11 partners)
Optimization of Protein Crystallization for European Structural Genomics
The key objective of the OptiCryst project is to address the critical post-protein production bottleneck area in the field of Structural Genomics. Moving away from current approaches, and applying methods based on understanding the fundamental principles of crystallization, the OptiCryst project focuses on designing techniques to actively control the crystallization environment as the project progresses through its stages.
Protein structures are pivotal to the success of rational drug design and other biotechnology applications; however obtaining high quality crystals still represents a major bottle-neck in the process. One of the Opticryst successes is a product Naomi's nucleants that entered the market a few months ago. The Opticryst consortium in search for a universal nucleant for protein crystallization developed a bio-glass nucleant with a highly porous surface that appears to be the most effective nucleant of any material tested. Naomi's Nucleants is the new product facilitating crystallization of proteins commercialized through Molecular Dimensions (SME, partner of the Opticryst project).