Role of Mediator in Heat Shock Gene Regulation

智力优势。 基因在染色体上呈线性排列，它们的基本特征在简单和复杂的生物体之间保持不变。 这项研究使用了一种模式生物，面包酵母（酿酒酵母），以探索基因调控的方式。 在酵母和人类中，基因要么被打开（激活），要么被关闭（抑制），这是特定蛋白质以序列特异性（基因特异性）方式结合DNA的结果。 这项研究将重点研究一个大型的，进化上保守的蛋白质复合物的详细作用，称为介体，它接收来自这些DNA结合蛋白的信号，并以一种决定单个基因表达的方式整合它们。 因此，中介功能类似于计算机：它以细胞内信号的形式处理大量输入信息，并创建输出，例如，基因表达的复杂模式，它定义了生物体或细胞类型的独特生物学。 这项研究将利用一组独特的基因突变内的五个亚基集中在调解人的核心。这些突变强烈干扰了对环境应激（如升高的温度、化学毒性或氧化应激）作出反应的基因的表达。 因此，对突变及其影响的五个亚基的表征，将为了解Mediator的生物学功能提供重要的见解。 这个项目的好处，超出了预期的科学发现，包括三个全职博士的培训。研究生，三名高中教师（他们将进行为期六周的暑期研究实习）和一名高中生。 高中生将从事密集的12个月的研究经验，作为LSU健康科学中心的科学和医学学术研究培训计划的参与者。

Intellectual Merit. Genes are linearly arrayed on chromosomes, and their basic features are preserved between simple and complex organisms. This research uses a model organism, baker's yeast (Saccharomyces cerevisiae), to explore the ways in which genes are regulated. In both yeast and humans, genes are either turned on (activated) or off (repressed) as a consequence of the activities of specific proteins that bind DNA in a sequence-specific (gene-specific) fashion. This research will focus on studying the detailed role of a large, evolutionarily conserved protein complex termed Mediator that receives signals from these DNA-binding proteins and integrates them in a way that dictates the expression of individual genes. Thus, Mediator function is akin to that of a computer: it processes large amounts of input information, in the form of intracellular signals, and creates an output, e.g., the complex pattern of gene expression that defines the unique biology of an organism or cell type. This research will take advantage of a set of unique genetic mutations within five subunits centered at Mediator's core. These mutations strongly perturb the expression of genes that respond to environmental stresses such as elevated temperature, chemical toxicity, or oxidative stress. Therefore, characterization of the mutations, and the five subunits they affect, will provide important insight into the biological function of Mediator.Broader Impacts. Benefits of this project, beyond the anticipated scientific discoveries, include the training of three full-time Ph.D. graduate students, three high school teachers (who will do summer research internships of six weeks each) and one high school student. The high school student will engage in an intensive 12-month research experience as a participant in LSU Health Science Center's Science and Medicine Academic Research Training program.