NSF Postdoctoral Fellowship in Biology FY 2013

2013 财年 NSF 生物学博士后奖学金

• 批准号: 1309306
• 负责人: David Bauer
• 金额: $ 14万
• 依托单位: Bauer David L
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309306&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; FY

Understanding the Librarians of the Genome: developing new physical assays to detect conformational changes in DNA-processing enzymesDNA polymerases, enzymes responsible for replicating and maintaining DNA in all domains of life, have been extensively studied over the past half-century. Despite the scrutiny, much remains unknown about the mechanism by which polymerases catalyze the building of a DNA strand and what limits their rate of reaction. Fluorescence techniques, Förster Resonance Energy Transfer (FRET) in particular, have allowed analysis of enzyme structure by using dyes as 'molecular rulers' of macromolecules. However, these methods cannot observe the smaller changes below 30 Å that occur at the active sites of enzymes. This project will extend FRET to the scale needed to study catalytic mechanisms of enzymes through the use of transition metal cation complexes as FRET acceptors over 10-20 Å, and examine the changes that occur in the active site of DNA polymerases. The proposed research and training plan lies at the intersection of biology (enzyme function, genetics) and physics (optics, photophysics). The applicant will gain training in the physical sciences, particularly on the theory and application of single-molecule FRET, the use of high-level optical instrumentation, and statistical data analysis, building upon the applicant's biology and genetics background. The extension of FRET to previously-inaccessible distances will find broad applicability to studying small structural changes in large molecules -- biological and otherwise. More broadly, this project facilitates broad dissemination of its results by integrating cutting-edge research with undergraduate education (course development, teaching and student mentoring) and public outreach via local partner organizations.

了解基因组的图书馆：开发新的物理检测来检测DNA加工酶的构象变化DNA聚合酶，负责复制和维持DNA在生命的所有领域的酶，在过去的半个世纪里得到了广泛的研究。尽管仔细研究，仍然有很多关于聚合酶催化DNA链构建的机制以及限制其反应速率的因素仍然未知。荧光技术，特别是Förster共振能量转移（FRET），已经允许通过使用染料作为大分子的“分子统治者”来分析酶的结构。然而，这些方法不能观察到在酶的活性位点发生的低于30 μ m的较小变化。本项目将通过使用10-20 μ m以上的过渡金属阳离子络合物作为FRET受体，将FRET扩展到研究酶的催化机制所需的规模，并检查DNA聚合酶活性部位发生的变化。拟议的研究和培训计划位于生物学（酶功能，遗传学）和物理学（光学，物理学）的交叉点。申请人将获得物理科学方面的培训，特别是关于单分子FRET的理论和应用，高级光学仪器的使用和统计数据分析，以申请人的生物学和遗传学背景为基础。将FRET扩展到以前无法到达的距离将发现广泛的适用性，以研究生物和其他大分子中的小结构变化。更广泛地说，该项目通过将尖端研究与本科教育（课程开发、教学和学生辅导）相结合，并通过当地伙伴组织开展公共宣传，促进其成果的广泛传播。