Minority Predoctoral Fellowship Program

描述（由申请人提供）：酿酒酵母可以通过启动复杂的遗传和生物化学程序来适应严重氧限制下的生长，该程序使细胞能够相应地调整其代谢以存活。我们一直致力于阐明一组专门在厌氧生长过程中表达的蛋白质的调控途径。我们感兴趣的是了解这些蛋白质在厌氧细胞中被打开的分子机制，以及它们在氧气存在下如何被抑制。在我们的研究过程中，我们已经确定了几个控制这种适应性反应的调节因素。我们正在使用分子遗传学和生物化学分析来描述这些厌氧蛋白的激活和抑制机制。这些因子中的一些已被证明在对唑类（靶向固醇生物合成的药物）敏感性降低的细胞中上调，而其他因子在被抑制时，细胞变得对这些药物敏感。这项工作将进一步我们的知识，什么可能被认为是一种类型的代谢诱导分化，并可能开辟一个相当广泛的调查领域，可能在抗真菌药物的开发。

DESCRIPTION (provided by applicant): Saccharomyces cerevisiae can adapt to growth under severe oxygen limitation by initiating a complex genetic and biochemical program that enable the cell to adjust their metabolism accordingly in order to survive. We have been engaged in elucidating the regulatory pathway of a specialized set of proteins that are expressed exclusively during anaerobic growth. We are interested in understanding the molecular mechanism by which these proteins are turned on in anaerobic cells and at the same time how they are kept repressed in the presence of oxygen. In the course of our study we have identified several regulatory factors which control this adaptive response. We are using molecular genetics and biochemical analyses to delineate the mechanisms of activation and repression of these anaerobic proteins. Some of these factors have been shown to be upregulated in cells with reduced susceptibility to azoles, drugs that target sterol biosynthesis while others when they are inhibited, the cells become susceptible to these drugs. This work will further our knowledge on what might be considered a type of metabolically induced differentiation and could open up a fairly extensive area of inquiry, possibly in antifungal drug development.