RUI: Uncovering Mechanisms of Spt16-gene Interactions

RUI：揭示 Spt16 基因相互作用的机制

• 批准号: 1613754
• 负责人: Andrea Duina
• 金额: $ 51.16万
• 依托单位: Hendrix College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1613754&HistoricalAwards=false
• 关键词: RUI; Uncovering; Mechanisms; Spt16; gene

The central objective of this project is to provide new insights into the molecular mechanisms that control how the information contained within genes is utilized by cells. Because genes are responsible for essentially all aspects of cell and organismal biology, ranging from how cells divide to how animals respond to hormones, these studies will shed new light into processes of broad biological importance. The project will also have a wide-reaching impact on the education of undergraduate students through the implementation of several initiatives. First, 12 undergraduate students will be directly involved in several aspects of the research. These students will be mentored by Dr. Duina and will be trained in a variety of laboratory and scientific skills. Second, 30-50 undergraduate students will carry out part of this research in the context of a course Dr. Duina teaches at Hendrix College. These students will be engaged in the excitement of science through an authentic research experience in the classroom. Third, students in Dr. Duina's laboratory will present their research to their peers majoring in disciplines other than the sciences. These sessions are designed to teach science students how to communicate science to the lay public as well as to expose non-scientists to the thrill of scientific inquiry.This research will focus on elucidating the mechanisms by which the transcription elongation factor Spt16 interacts with transcribed genes in vivo. Within the nucleus of eukaryotic cells, DNA is compacted through the formation of a protein-DNA complex known as chromatin, the fundamental unit of which is the nucleosome. Nucleosomes consist of a short stretch of DNA wrapped around histone octamers, themselves composed of pairs of the four core histone proteins. Nucleosomes represent physical barriers during the process of gene transcription and Spt16, as part of the FAcilitates Chromatin Transactions (FACT) complex, has been shown to play central roles in overcoming these barriers. In this project, Dr. Duina's laboratory will use a combination of genetic, biochemical, and targeted proteomic approaches to assess contributions of DNA sequences, histone modifications, histones, and other proteins in regulating physical interactions between Spt16 and transcribed genes. The model organism Saccharomyces cerevisiae will be used for this project, and given the high degree of evolutionary conservation in the factors and processes under investigation, results from these studies will contribute to our understanding of a process relevant to all eukaryotic organisms, including humans.This project is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.

该项目的中心目标是为控制细胞如何利用基因中包含的信息的分子机制提供新的见解。 由于基因基本上负责细胞和生物体生物学的所有方面，从细胞如何分裂到动物如何对激素做出反应，这些研究将为具有广泛生物学重要性的过程提供新的见解。 该项目还将通过实施若干举措，对本科生的教育产生广泛影响。 首先，12名本科生将直接参与研究的几个方面。 这些学生将由杜伊纳博士指导，并将接受各种实验室和科学技能的培训。 第二，30-50名本科生将在杜伊纳博士在亨德里克斯学院教授的课程中进行部分研究。 这些学生将通过在课堂上真实的研究体验参与科学的兴奋。 第三，杜伊纳博士实验室的学生将向他们的同龄人展示他们的研究，而不是科学专业。 这些会议旨在教理科学生如何沟通科学的外行公众以及暴露非科学家的科学调查的兴奋。这项研究将集中在阐明转录延伸因子Spt 16与转录基因在体内相互作用的机制。在真核细胞的细胞核内，DNA通过形成称为染色质的蛋白质-DNA复合物而被压缩，染色质的基本单位是核小体。 核小体由一小段DNA包裹在组蛋白八聚体周围组成，八聚体本身由四种核心组蛋白组成。 核小体是基因转录过程中的物理屏障，Spt 16作为FACT复合物的一部分，已被证明在克服这些屏障中发挥核心作用。 在这个项目中，Duina博士的实验室将使用遗传，生物化学和靶向蛋白质组学方法的组合来评估DNA序列，组蛋白修饰，组蛋白和其他蛋白质在调节Spt 16和转录基因之间的物理相互作用中的贡献。 该项目将使用模式生物酿酒酵母（Saccharomycescerevisiae），鉴于所研究的因子和过程具有高度的进化保守性，这些研究的结果将有助于我们理解与所有真核生物（包括人类）相关的过程。