Bioelectrical signals in controlling the morphogenesis of the embryonic stem cells

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Understanding mechanisms that control proliferation and movement of cells is an essential component of efforts to prevent, detect, and treat cancer. Most current efforts focus on biochemical signaling factors and gene transcription networks. Complementary to this approach, this research proposes to understand, at the molecular level, epigenetic biophysical controls of cell behavior. Using multi-disciplinary approaches (molecular genetics and in vivo physiology) this proposed project will address the roles of ion flows as an endogenous regulator of cell type, position, and differentiation. By discovering and characterizing novel roles of ion transporters, H+ and K+ flows (and pH and membrane voltage gradients) have been already implicated in left-right patterning, spinal cord/muscle regeneration, and eye development. Tumor cells often differ from normal cells in their intracellular pH and membrane voltage potential. Numerous data indicate that these bioelectrical parameters are not simply house-keeping byproducts of other events but are rather instructive, functional signals by means of which cell behavior can be controlled. One of the most striking examples for this is distinct polarity and directional movement of cells, both crucial for development and tissue remodeling, under physiological electric fields. The research proposes to capitalize on the expertise in manipulating and characterizing bioelectrical events, as well as on a model system that is highly tractable and amenable to state-of-the-art techniques of molecular genetics and physiology, to make progress in this novel but very important aspect of cancer biology.