Probing protein aggregation with small molecules

用小分子探测蛋白质聚集

• 批准号: RGPIN-2019-04818
• 负责人: NekkarRao, Praveen
• 金额: $ 2.62万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=686773
• 关键词: Probing; protein; aggregation; small; molecules

Research summary: Proteins are important biomolecules that play a significant role in normal body function. Among the many and diverse proteins in mammals, some proteins lack proper structures and tend to undergo misfolding to form protein aggregates or clumps. These partially disordered protein aggregates can be toxic to cells. The mechanisms involved in the formation of protein aggregates, is not clearly understood. My proposal, aims to answer these questions by developing novel molecules as cutting-edge tools to study the mechanisms of protein aggregation. Molecular libraries will be prepared and biochemical studies will be carried out to monitor protein aggregation by using a number of techniques which will assist in elucidating the critical regions involved in protein aggregation at the molecular level. Furthermore, these investigations will be supported by computational modeling to determine the nature of protein-protein and protein-small molecule interactions. We anticipate that these studies will advance our current knowledge by elucidating the mechanisms of protein aggregation pathway that has broad applications in science and technology. ******Student training: Our proposed research program will train several graduate and undergraduate students over the next five years. Students will be trained in a number of research techniques which will provide the necessary skill sets to succeed in academic or industrial settings as future scientists and contribute to the growth of scientific and economic landscape of Canada.**

研究概述：蛋白质是重要的生物分子，在正常的身体功能中起着重要的作用。在哺乳动物的许多不同的蛋白质中，一些蛋白质缺乏适当的结构并且倾向于经历错误折叠以形成蛋白质聚集体或团块。这些部分无序的蛋白质聚集体可能对细胞有毒。蛋白质聚集体形成的机制尚不清楚。我的提案旨在通过开发新分子作为研究蛋白质聚集机制的尖端工具来回答这些问题。将准备分子库，并将进行生物化学研究，以监测蛋白质聚集，通过使用一些技术，这将有助于阐明在分子水平上蛋白质聚集所涉及的关键区域。此外，这些研究将得到计算机建模的支持，以确定蛋白质-蛋白质和蛋白质-小分子相互作用的性质。我们期望这些研究将通过阐明在科学和技术中具有广泛应用的蛋白质聚集途径的机制来推进我们现有的知识。** 学生培训：我们拟议的研究计划将在未来五年内培训几名研究生和本科生。学生将接受一些研究技术的培训，这些技术将提供必要的技能，以在学术或工业环境中取得成功，成为未来的科学家，并为加拿大科学和经济格局的发展做出贡献。