Functions of VAMP proteins in glial cells

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Our project addresses a key question in neuroscience, namely how cells of the central nervous system interact to assure its proper development and function. We focus on glial cells that surround synaptic connections between neurons, and we aim to test a long-standing hypothesis that these cells influence the development and function of neurons by the vesicular transport and release of substances. To test this hypothesis, we combine new and unique experimental approaches that we have developed within the last years including new transgenic mouse models and methods to assess the morphology and physiology of glial cells. Our project follows up and extends a previous collaboration of the partners that has led to a first recent publication. Concretely, we will investigate how elimination of several so-called vesicle-associated membrane proteins (VAMPs) in glial cells affects the physiologic properties of glial cells and the histology and ultrastructure of selected brain regions. Members of the VAMP family are highly conserved and ubiquitously expressed components of protein complexes that catalyse the targeted fusion of membranes and thereby mediate the intracellular transport of vesicles between organelles. This is a key process of eukaryotic cells. We note that previous research has focused almost exclusively on the functions of VAMPs in neurons, and their role in glial cells has been neglected for a long time. We hope that the results of our exploratory two-year project will enable an expansion of the proposal and the demand of grants in the future. Our project relies entirely on a bilateral cooperation between a French and a German partner, who both have a common and long-standing interest and track record in neuron-glia interactions and who command highly complementary methods that will enable an efficient execution of the project. This project falls in the category of fundamental research, but our results may have implications for R&D in the pharmaceutical and biotechnological industry, if they uncover glial signaling pathways as potential therapeutic targets for brain diseases. Last not least, we hope that our transnational project will advance neuroscience in France and Germany and strengthen the position of our countries in a field of research that is highly competitive at an international level.