Minority Predoctoral Fellowship Program

描述(申请人提供)：酿酒酵母可以通过启动复杂的遗传和生化程序来适应严重氧气限制下的生长，使细胞能够相应地调整自己的新陈代谢以求生存。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启动的分子机制，以及同时它们如何在氧气存在的情况下被抑制。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化分析来描述这些厌氧蛋白的激活和抑制机制。这些因素中的一些已经被证明在对唑类药物敏感性降低的细胞中上调，这些药物是针对类固醇生物合成的药物，而另一些当它们被抑制时，细胞对这些药物变得敏感。这项工作将进一步加深我们对可能被认为是一种代谢诱导分化的认识，并可能打开一个相当广泛的研究领域，可能是在抗真菌药物开发方面。

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.