Cell polarization describes the ability of a cell to use external and/or internal stimuli to decide in which direction to grow, crawl or divide. Cells can sense different cues in vivo such as chemical gradients, sites of cell adhesion, and electric fields. In this proposal, we aim at investigating the electrical aspects of cell polarization. Endogenous electrical signals are present around tissues in the body, yet their possible contribution in globally organizing spatial aspects of cell polarity remains poorly appreciated. Steady electric fields (EFs) have been measured across epithelial layers and may guide cell polarity in wound healing, metastasis and development. Even single cells organize trans-cellular ion currents, through asymmetries in ion transporters localization, which contributes to the regulation of polarity. It has long been observed that the exogenous application of an EF, similar to those measured in vivo, can direct polarity, migration and division in cell types ranging from bacteria to mammalian cells. Application of EFs has potential clinical value, for instance in wound healing and tissue engineering. The mechanisms by which cells generate or sense EFs remain however poorly described. In here, we propose a global multidisciplinary approach to study these aspects. We will use the genetic model organisms, fission and budding yeast as rigorous quantitative systems to derive molecular mechanisms. In a first aim, we will characterize and manipulate trans-cellular loops of ion fluxes around yeast cells to test their role in cell polarity. In a second aim, we propose to perform genome-wide screens on EF effects on the polarity of these cells. Finally in a third aim we will use EFs to control the position of different proteins in cells. These studies promise to bring novel understanding in the mechanisms of cell polarization, and will open new synthetic ways to control and manipulate polarity in cells and tissues.
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