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

极化形态发生中的氧甾醇结合蛋白：囊泡的交叉点

• 批准号: 0723342
• 负责人: Keith Kozminski
• 金额: $ 50.87万
• 依托单位: University of Virginia Main Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-10-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0723342&HistoricalAwards=false
• 关键词: Oxysterol; Binding; Proteins; Polarized; Morphogenesis

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.

智力优势：合理控制大多数细胞的生长和特化的能力需要细胞如何不对称生长的知识。 不对称增长，即，只向细胞的一极生长，是不同物种生存和繁殖所必需的。 这个项目是一个长期努力的一部分，旨在破译允许真菌，植物和动物细胞只在一个极点生长的细胞事件。 本项目主要研究面包酵母的极性生长。酿酒酵母），因为易于实验操作，其与其他真菌以及植物和动物细胞的已知相似性，以及作为研究工具的相对低的成本。 本项目的重点是确定奥什蛋白在不对称生长过程中的功能。 奥什蛋白是哺乳动物氧化固醇结合蛋白（OSBPs）的真菌等价物，OSBPs是结合固醇如胆固醇的功能上神秘的蛋白质家族。虽然已知奥什蛋白是生命所必需的，并且对于极性细胞生长是重要的，但是这些蛋白如何起作用还没有很好的定义。 此外，并非所有的奥什蛋白都具有明确的甾醇结合区。该项目的一部分实验将回答关于奥什蛋白如何在细胞中发挥作用的一个基本问题：甾醇分子与奥什蛋白的结合是否是奥什蛋白发挥作用所必需的，即，奥什蛋白质是否具有依赖甾醇和不依赖甾醇的功能？ 在这个项目的其他部分的实验使用酵母菌株缺乏奥什蛋白来区分几个模型来解释极性细胞生长的基本方面。 具体的重点是确定细胞如何保持信号极性细胞生长（高度保守的GTP结合蛋白Cdc 42）在极的细胞指定的增长。因此，除了确定细胞中奥什蛋白功能所需的内容外，该项目还将揭示细胞调节极性细胞生长的部分细胞机制。更广泛的影响：研究生和本科生将与PI一起参与该项目。 该项目的实验将被纳入本科实验室课程，这将使更多的学生接触到“真实的”研究。 最后，PI将参加弗吉尼亚大学K-12外展计划，以促进科学和科学事业。