CAREER:The Role of the Protein Kinase C Pathway and Chromatin Remodeling Factors in Orchestrating the Environmental Stress Response in Yeast

所有生物都必须能够感知环境，并对环境压力进行适当的防御。该项目将研究复杂的调节网络，协调酵母的环境应激反应（ESR）。ESR由约900个基因表达变化组成，这些变化可被不同的应激激活。实验计划测试蛋白激酶C （PKC）信号网络和染色质重塑蛋白在调节ESR响应特定应激中的作用。利用DNA微阵列，可以在一次实验中测量酵母基因组中每个单个基因的表达水平。酵母微阵列将用于跟踪野生型细胞和PKC信号缺陷细胞的全基因组表达，因为细胞对应激作出反应。数据的计算分析将识别出网络中表达依赖于不同调节蛋白的基因，从而使研究人员能够绘制出应激反应中信号转导的路径。这些结果将为细胞如何协调包括ESR在内的复杂细胞反应提供见解，并将阐明PKC信号网络。这项工作的一个重要组成部分是在威斯康星大学麦迪逊分校开设了一门新的计算基因组学课程，专门针对训练生物学家进行大数据集的统计和计算分析。

All organisms must be able to sense their environment and mount the appropriate defenses against environmental stress. This project will examine the complex regulatory network that orchestrates the environmental stress response (ESR) in yeast. The ESR consists of ~900 gene expression changes that are activated by diverse stresses. Experiments are planned to test the role of the Protein Kinase C (PKC) signaling network and chromatin remodeling proteins in regulating the ESR in response to specific stresses. Using DNA microarrays, it is possible to measure the expression level of every single gene in the yeast genome in one experiment. Yeast microarrays will be used to follow whole-genome expression in wild-type cells and in cells defective in PKC signaling, as cells respond to stress. Computational analysis of the data will identify genes whose expression is dependent on different regulatory proteins in the network, thus allowing the investigators to map the path of signal transduction in response to stress. These results will provide insights into how cells orchestrate complex cellular responses, including the ESR, and will shed light on the PKC signaling network. A significant component of this work is the development of a new computational genomics course at UW-Madison, specifically aimed at training biologists in statistical and computational analysis of large datasets.