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SIGNALLING & TRAFFIC Résumé de rapport

Project ID: 503228
Financé au titre de: FP6-LIFESCIHEALTH
Pays: France

Final Report Summary - SIGNALLING & TRAFFIC (Signalling and membrane trafficking in transformation and differentiation)

Cancer and brain-related diseases are two of the principal causes of morbidity and mortality in Europe and diseases with major socio-economic impact. Our research is ultimately finalised to develop targets for therapeutic procedures and new diagnostic tools to better the health conditions and ultimately the standard of living. From the public health point of view, the social impact of our research is only too obvious. In addition, from the economical point of view, sensible gains are to be projected for the various national health systems, once more potent management tools will be available, by reducing, for example, the need for radical intervention and therefore save on the ensuing rehabilitation costs.

In the case of cancer, the ultimate goal indeed is to shift the therapeutic emphasis, for some tumours, from surgical to pharmacological intervention, thus limiting the hospitalisation costs and the financial, psychological and physical burden on the patients and their families. In the case of neurodegenerative diseases such as Alzheimer's, Hungtington's disease and neuropathies, the lack of an understanding of the complex physiopathological links between gene defects and symptoms and the absence of efficient therapeutics demonstrate the need to search for new strategies. Several of the gene products that have been studied in this project (rab proteins and their partners, SNAREs and their partners, growth factors, cell adhesion molecules and metalloproteases) have already been linked to cancer and brain-related diseases.

We intended to foster education, training and exposure of young scientists to cultural diversity, both from the scientific and social point of view. SIGNALLING AND TRAFFIC offered training opportunities for technicians, PhD students and post-doctoral fellows to perform their own professional scientific development in a highly skilled and competitive consortium. The participating laboratories offered, in our admittedly 'biased' assessment, the highest standards of scientific rigor and international competitiveness and therefore provided an excellent opportunity for younger scientist to develop to full maturity and start their own scientific enterprises. We gave particular attention to maintaining the gender balance at all levels and to involving the most promising fellows in the inter-group meetings, to offer them the opportunity of travelling, coming into contact with new scientific and national realities and participating in the management of science. Standard scientific dissemination through congresses, workshops and publications, and in classes in the universities of the participants serve as important vehicles for information transfer and training.

Our website (please see was the core of the communication of the network with students. Through this platform, we have tried to foster education on the molecular and cellular basis of signalling and traffic in normal and pathological situations. We particularly emphasised the molecular and cellular mechanisms of cancer, brain degenerative diseases and neuropathies that have a signalling and traffic component. Additionally public awareness actions designed to inform the general public of 'research' and the 'benefits of research to society' were performed by the partners and through our final public meeting.

Our goal was to establish the connections between signalling pathways and membrane trafficking in the context of highly dynamic migrating, dividing and adhering mammalian cells. Through the study of membrane traffic in the course of cell differentiation, de-differentiation, and during mitosis, we aimed to unravel how important signalling pathways remodel the intracellular trafficking routes and conversely, how membrane traffic can influence signalling cascades. Using modern cell biological approaches, we studied several cellular models including neurons differentiating in culture and establishing contacts and cancer cells dividing and migrating. We investigated proteins that play central roles in membrane trafficking and secretion such as rabs, SNAREs and their partners. We focused on the trafficking of signalling molecules including cell-cell and cell-substrate adhesion molecules, growth factors and their receptors. Through these approaches we have started to define the connections between signalling and traffic in normal and pathological conditions.

Our wish was to be able to unravel the links between membrane trafficking and cell signalling leading to cancer and brain diseases. We have already made very significant progress towards this goal. In order to achieve all of their goals, the participants have intensively exchanged data, reagents, and students and have decided to even increase the exchange of scientists during the second term of the project. While most if not all deliverables and milestones have been achieved, the collaborations initiated in this consortium will continue in the next few years.

Each member of the consortium is already involved in the dissemination of the knowledge generated in this STREP in his / her home country. As a common action, we decided to organise a European meeting, free, open to the public and advertised. This meeting took place in Heidellberg in October 2007 at the end of the STREP. We presented our own work and invited two other scientists working in the same field: Jean Gruenberg and Ivan Dikic as speakers. We also extended the invitation to biotechnology companies interested by the link between signalling and trafficking.

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