NSF Minority Postdoctoral Fellowship for FY 2009

2009 财年 NSF 少数族裔博士后奖学金

• 批准号: 0905878
• 负责人: Lucas Nivon
• 金额: $ 18.9万
• 依托单位: Nivon Lucas G
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0905878&HistoricalAwards=false
• 关键词: NSF; Minority; Postdoctoral; Fellowship; FY

This action funds an NSF Minority Postdoctoral Research Fellowship for FY 2009 and is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). The fellowship supports a research and training plan in a host laboratory for the Fellow who also presents a plan to broaden participation in biology. The title of the research and training plan for this fellowship to Lucas Nivon is "Computational design of new enzymes: catalyzing carbon-carbon bond formation in bi-molecular reactions." This research is being conducted at The University of Washington under the sponsorship of Dr. David Baker. Enzymes are responsible for the wide variety of metabolic functions in living organisms but natural enzymes cannot catalyze most commercially important synthetic reactions. This research tests current understanding of enzyme function by using chemical principles to computationally design new enzymes for non-natural reactions. Novel enzymes have been successfully produced for a retro-Aldol (RA) addition and the Kemp elimination by using new algorithms to search for appropriate active sites and to design atomically-accurate pockets to bind the transition states of particular chemical reactions. These reactions are uni-molecular. This project is tackling bimolecular, bond-forming reactions by studying 2 reactions closely related to the RA (Michael addition and forward Aldol addition) by re-designing RA enzymes for these bimolecular reactions. Additionally under study is the Morita-Bayliss-Hillman (MBH) reaction, which is widely applied in modern syntheses, but is nonexistent in nature, to ask whether enzymes can catalyze a reaction previously known only to synthetic chemistry.Training plans include learning computational methods of protein design and the biochemical skills necessary to perform a wide range of enzymatic assays and large-scale enzyme purifications. By using established theories of enzyme function to design new proteins this project will critically test those theories and perhaps reveal new basic principles of enzyme function. Outside of pure biochemistry this work is useful for biotechnology and medicine, allowing the design of new enzymes for industrial applications or for use as enzyme drugs or diagnostics. Broader impacts also include educational outreach to students, especially from under-represented groups.

这项行动为2009财年的NSF少数民族博士后研究奖学金提供资金，并根据2009年美国复苏和再投资法案（公法111-5）提供资金。该研究金支持研究员在东道实验室的研究和培训计划，研究员还提出了扩大生物学参与的计划。Lucas Nivon的研究和培训计划的标题是“新酶的计算设计：催化双分子反应中的碳-碳键形成”。“这项研究是在大卫贝克博士的赞助下在华盛顿大学进行的。酶负责生物体中各种各样的代谢功能，但天然酶不能催化大多数商业上重要的合成反应。这项研究通过使用化学原理来计算设计用于非自然反应的新酶来测试当前对酶功能的理解。通过使用新的算法来搜索合适的活性位点并设计原子精确的口袋来结合特定化学反应的过渡态，已经成功地产生了用于逆羟醛（RA）加成和肯普消除的新型酶。这些反应是单分子的。 该项目通过研究与RA密切相关的2个反应（Michael加成和正向Aldol加成）来解决双分子成键反应，并通过重新设计RA酶来进行这些双分子反应。此外，正在研究的是Morita-Bayliss-Hillman（MBH）反应，该反应在现代合成中被广泛应用，但在自然界中并不存在，以询问酶是否可以催化以前仅在合成化学中已知的反应。培训计划包括学习蛋白质设计的计算方法以及进行广泛的酶测定和大规模酶纯化所需的生物化学技能。通过使用酶功能的既定理论来设计新的蛋白质，该项目将严格测试这些理论，并可能揭示酶功能的新的基本原理。在纯生物化学之外，这项工作对生物技术和医学很有用，可以设计用于工业应用或用作酶药物或诊断的新酶。 更广泛的影响还包括对学生，特别是代表性不足群体的学生进行教育宣传。