Folding and Aggregation of Polyglutamine Peptides and Proteins

该奖项是根据2009年美国复苏和再投资法案（公法111 - 5）资助的。0852278Murphy智力价值蛋白质聚集的实验和理论研究大大落后于蛋白质折叠的研究，因为他们更大的复杂性。一些研究人员已经开发了蛋白质错误折叠和聚集的分子动力学模拟，但这些模拟的预测尚未经过实验验证。在该项目中，将合成多聚谷氨酰胺（polyQ）肽和蛋白质的"长度文库"，并对其构象特性和聚集倾向进行表征。 肽和蛋白质的聚集给生物技术和生物医学带来了重大挑战。例如，超过450万美国人患有与聚集相关的神经退行性疾病。作为另一个实例，治疗性重组蛋白制剂中的聚集体降低药理学效率，并且可能通过引起严重的免疫应答而威胁患者的健康。解读聚集的原因是制定控制聚集的合理战略的第一步。该项目的研究生在蛋白质和肽折叠和错误折叠的现代实验和计算方法方面受到广泛的教育，并准备在学术界或生物技术行业发挥主导作用。通过积极参与暑期研究计划，代表性不足的少数民族本科生将获得宝贵的经验，并享受成就感，这将有助于他们对研究事业的持续热情。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).0852278Murphy Intellectual merit Experimental and theoretical studies of protein aggregation lag considerably behind protein folding studies, because of their much greater complexity. Several researchers have developed molecular dynamics simulations of protein misfolding and aggregation, but the predictions from these simulations have not been experimentally tested. In this project, 'length libraries' of polyglutamine (polyQ) peptides and proteins will be synthesized and characterized for their conformational properties and aggregation propensities.Broader impacts Aggregation of peptides and proteins pose significant challenges in both biotechnology and biomedicine. For example, over 4.5 million Americans suffer from aggregation-linked neurodegenerative diseases. As another example, aggregates in therapeutic recombinant protein preparations reduce pharmacological efficiency, and can threaten patients' health by causing serious immunological responses. Deciphering the causes of aggregation is the first step towards developing rational strategies for controlling aggregation. Graduate students on this project are broadly educated in modern experimental and computational approaches in protein and peptide folding and misfolding, and prepared to take leading roles in academia or in the biotechnology industry. Through active participation in a summer research program, underrepresented minority undergraduates will gain valuable experience and enjoy a sense of accomplishment that will contribute to their continued enthusiasm for research careers.