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Research at UMR 6184

Laboratory : Neurobiology of Cellular Interactions and Neurophysiopathology ; N.I.C.N. Mixed Research Unit (UMR) 6184, CNRS-Université de la Méditerranée. Director, Michel Khrestchatisky

Most pathologies and lesions of the nervous system (NS) are associated with neurodegenerative processes, neuronal plasticity and glial reactivity. These processes are modulated by neuroinflammation and may involve tissue repair with the formation of glial scars, and eventually a contribution of neural stem cells in plasticity and repair. Understanding the physiopathological processes involved in nervous system diseases involves a better understanding of interactions between neurones, glial cells and infiltrating cells of the immune system, and the underlying molecular mechanisms.

The main objectives of the UMR6184 research laboratory are to study the molecular mechanisms that regulate cell interactions in pathological and plasticity processes of the NS, to develop cell therapy approaches in the NS, using differentiated neural cells and neural stem cells from the adult. Our approaches are two sided : i) in vitro, with cell lines, but also with primary cultures of neural cells ; ii) in vivo, with invertebrate and mammalian animal models, knock out or transgenic for genes of interest, in order to address our questions in a physiopathological context. A wide scope of techniques are used in the laboratory ranging from cell biology, molecular biology, biochemistry, proteomics and imaging, and the laboratory benefits from the mutualisation of technology platforms of the Jean-Roche Federative Research Institute (IFR Jean-Roche). Four research teams with complementary competences are actually grouped to address the objectives described above.

- The team directed by Drs. Santiago Rivera and Michel Khrestchatisky studies neuronal death, neuronal plasticity, both reactive and physiological, and more specifically, addresses the role of extracellular proteolysis of extracellular matrix, signalling and membrane bound proteins by matrix metalloproteinases (MMPs) in these processes.
- The team directed by Dr. José Boucraut studies neuro-inflammation that results from the interaction between cells of the immune and nervous systems such as in multiple sclerosis (MS) and in experimental autoimmune encephalopathy (EAE), an animal model of MS, and is focused on studying the role of classical and non classical MHC molecules in the NS.
- The team of Dr. Catherine Faivre-Sarrailh studies cell adhesion molecules in mammals and drosophila and interactions between neurones and glial cells in myelination, notably in connection with MS.
- Finally, the group directed by Pr. François Féron is specialised in the olfactory system in mammals and in C. elegans and exploits the unique potential of neural cells from the olfactory mucosa to develop cell therapy approaches in lesions and pathology of the spinal cord and brain, and develops a research axis on olfactory imprinting and its relation to epigenetics.

Since march 2005, the four research teams are located in a renovated and fully equipped laboratory in the Medical Faculty of Marseilles (Secteur Nord) where they share the ambition of recruiting established researchers, post docs and doctoral students for the development of their projects, in the context of local, national and international collaborations. Members of the laboratory are involved in teaching and training, in particular in the Neuroscience and Health Master programs proposed by the University of Marseille. Some members of the laboratory also invest substantial efforts in transfer of results and competences to medical and applied research. Dr. José Boucraut and his MD colleagues (Pr. Dominique Bernard, Dr. Sophie Desplat Jego) run the “Service d’Immunologie” of the Hôpital de la Conception in Marseille (diagnosis of NS pathologies and medical research on autoimmune and neuro-immune diseases). Pr. François Féron, Drs. José Boucraut and Sophie Desplat Jego have set up the “cell therapy of the nervous system” facility in the Center of Cell therapy of the Hôpital de la Conception in Marseille. Finally, based on his ongoing research, Dr. Michel Khrestchatisky has recently created a biotechnology company dedicated to the characterisation of molecules that cross the blood brain barrier and that will be developed as vectors for therapeutic agents and imaging molecules to be addressed to the central nervous system.

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