Oxysterol Binding Proteins in Polarized Morphogenesis : Intersection of Vesicular & Non-vesicular Traffic

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Intellectual Merit:The ability to rationally control the growth and specialization of most cells requires knowledge of how cells grow asymmetrically. Asymmetric growth, i.e., growth exclusively toward one pole of a cell, is necessary for the survival and propagation of diverse species. This project is part of a long-term effort to decipher cellular events that allow fungi, plants, and animal cells to grow exclusively at one pole. This project is to study polar growth in baker's yeast (S. cerevisiae) because of ease of experimental manipulation, its known similarity to other fungi as well as plant and animal cells, and comparatively low cost as a research tool. This project focuses on determining the function of Osh proteins during the process of asymmetric growth. Osh proteins are the fungal equivalent of mammalian oxysterol sterol binding proteins (OSBPs), a functionally enigmatic protein family that binds sterols such as cholesterol. Although it is known that Osh proteins are essential for life and important for polar cell growth, how these proteins function is not well defined. Moreover, not all Osh proteins share a clear sterol binding region. Experiments in one part of the project will answer a fundamental question about how Osh proteins function in cells: Is the binding of a sterol molecule to an Osh protein necessary for Osh protein function in general, i.e., do Osh proteins have sterol-dependent as well as sterol-independent functions? Experiments in the other part of this project use yeast strains lacking Osh proteins to distinguish between several models to explain basic aspects of polar cell growth. Specific focus is given to determining how cells keep a signal for polar cell growth (the highly conserved GTP binding protein Cdc42) at the pole of the cell designated for growth. Thus, in addition to determining what is required for Osh protein function in cells, this project will reveal part of the cellular mechanism by which cells regulate polar cell growth.Broader Impact:Graduate and undergraduate students will participate in the project, working with the PI. Experiments from the project will be included in an undergraduate lab course, which will expose more students to "real"research. Finally, the PI will participate in a University of Virginia K-12 outreach program to promote science and careers in science.