GENETIC CHARACTERIZATION OF TWO GENES INVOLVED IN YEAST PROGRAMMED CELL DEATH

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞程序性死亡（PCD）是多细胞生物重要的生理过程，也是重要的抗肿瘤防御机制。有些人甚至将逃避程序性细胞死亡的能力称为“癌症的标志”。 芽殖酵母，酿酒酵母，作为一个有用的模型，复杂的生理过程的后生动物细胞，包括PCD。许多工作都试图描述驱动程序性细胞死亡的分子机制。 在过去的四年里，我在普罗维登斯学院的实验室研究了UTH 1和BXI 1，这两个基因与酵母中的程序性细胞死亡有关。 我们已经产生了缺乏UTH 1和BXI 1的突变体，并表明它们具有分别将它们与细胞壁和未折叠蛋白反应连接的表型。该提案概述了确定UTH 1和BXI 1功能所涉及的分子途径的遗传策略。 它将利用酵母系统相对于哺乳动物系统的主要优势，作为程序性细胞死亡的模型系统：酵母细胞适合遗传分析，使研究人员能够快速识别生物过程的分子途径。 本提案中描述的遗传策略将寻求澄清UTH 1，BXI 1和酵母中其他PCD基因之间的遗传关系，以确定调节该生物体中程序性细胞死亡的分子途径。 鉴于不同物种的细胞凋亡途径的显着保护，这种分析应该导致进一步深入了解类似的过程，在高等生物体，包括人类。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Programmed cell death (PCD) is both an important physiological process and a significant anti-tumor defense mechanism in multicellular organisms. Some have even called the ability to evade programmed cell death a "hallmark of cancer". The budding yeast, Saccharomyces cerevisiae, has served as a useful model for complex physiological processes of metazoan cells including PCD. Much work has gone into attempting to describe the molecular mechanisms that drive programmed cell death. For the past four years, my laboratory at Providence College has studied UTH1 and BXI1, two genes linked with programmed cell death in yeast. We have generated mutants lacking UTH1 and BXI1 and have shown that they have phenotypes linking them to the cell wall and the unfolded protein response respectively. This proposal outlines genetic strategies to identify the molecular pathways involved in UTH1 and BXI1 function. It will exploit the primary advantage of the yeast system over its mammalian counterpart as a model system for programmed cell death: Yeast cells are amenable to genetic analysis that allows investigators to identify rapidly molecular pathways underlying a biological process. The genetic strategies described in this proposal will seek to clarify the genetic relationships between UTH1, BXI1, and other PCD genes in yeast to identify the molecular pathways that regulate programmed cell death in this organism. Given the remarkable conservation of the apoptotic pathways across diverse species, this analysis should lead to further insights into the analogous processes in higher organisms including human beings.