Investigating protein aggregation with small molecules

研究小分子蛋白质聚集

• 批准号: RGPIN-2014-03830
• 负责人: NekkarRao, Praveen
• 金额: $ 2.99万
• 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: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=566115
• 关键词: Investigating; protein; aggregation; small; molecules

Research Summary: Among the many and diverse proteins in mammals, some proteins can misfold and form aggregates. Studies indicate that these partially disordered protein aggregates can be toxic to cells. However the exact nature of protein misfolding and aggregation is still a work in progress. In our proposal we are aiming to answer these questions, by using small molecules as tools to study the mechanisms of protein aggregation. Small molecule libraries will be synthesized and biochemical studies will be conducted to monitor protein aggregation kinetics by a number of techniques. These studies 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-small molecule interactions and their role in protein aggregation/disaggregation. We anticipate that these studies will advance our current knowledge by elucidating the mechanisms of protein aggregation pathway and will assist in developing novel tools to study protein aggregation. HQP 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 in Canada.

研究综述：在哺乳动物众多而多样的蛋白质中，一些蛋白质可以错误折叠并形成聚集体。研究表明，这些部分无序的蛋白质聚集体可能会对细胞产生毒性。然而，蛋白质错误折叠和聚集的确切性质仍在进行中。在我们的提案中，我们的目标是通过使用小分子作为工具来研究蛋白质聚集的机制来回答这些问题。将合成小分子文库，并将通过多种技术进行生化研究，以监测蛋白质聚集动力学。这些研究将有助于在分子水平上阐明参与蛋白质聚集的关键区域。此外，这些研究将得到计算机模拟的支持，以确定蛋白质-小分子相互作用的性质及其在蛋白质聚集/解聚中的作用。我们期待这些研究将通过阐明蛋白质聚集途径的机制来促进我们现有的知识，并将有助于开发新的工具来研究蛋白质聚集。HQP培训：我们提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方面的培训，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。