Non-covalent Complexes

非共价配合物

• 批准号: 0909743
• 负责人: Michael Bowers
• 金额: $ 73万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0909743&HistoricalAwards=false
• 关键词: Non; covalent; Complexes

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). In this award funded by the Experimental Physical Chemistry Program of the Division of Chemistry, Professor Michael Bowers of University of California, Santa Barbara, explores the question of why peptides and proteins in living systems are soley composed of L-amino acids - one of the deepest mysteries in biology. Professor Bowers and his students will start with several simple model systems of peptides that are available in a wide range of chirally mixed forms. These peptides are small enough (5 or 6 amino acids long) that good theory can be done on them to help understand observed changes in their folding and aggregation tendencies as a function of their chiral purity. These peptide families will also provide an entrée into a second major thrust of the proposal - amyloid formation mechanisms. Amyloids are ubiquitous in complex living systems and are implicated in many serious diseases (Alzheimer's, type 2 diabetes, etc.). The goal is to understand the aggregation process and how initially coiled or alpha-helical oligomeric systems end up as large beta-sheet assemblies. As part of this effort Professor Bower's team will initiate a collaboration with Gerhard Meijer and Gert Von Helden at the Fritz Haber Institute in Berlin. This group is building a state of the art instrument to Professor Bower's specifications for this work to couple with a new free electron laser under construction at that facility. Finally the researchers have initiated studies on a related biologically important amyloid system, the 37 residue IAPP or amylin peptide, involved in type 2 diabetes. The human wild type peptide rapidly forms large oligomers but a number of very similar peptides do not. Preliminary data implicate compact assemblies as leading to fibril formation (and hence disease) while elongated assemblies of the same oligomer number do not aggregate further. Modeling and further experiments are planned to fully understand these initial results. Science education in the United States is in a sustained downturn that threatens our world leadership in both innovation and technology development. The problems start early. The 5th grade has been targeted as the first "go" or "no go" indicator in a child's scientific development. At UCSB there is a strong outreach program at the 5th grade level initiated and sustained by a former group member with continuing help from current research group members. Professor Bowers decided to tackle the second "go" or "no go" decision time in young adults - their high school years. His group is developing an outreach program using all group members to present their research projects to high school classes and to relate their personal scientific stories and how they ended up in graduate school at UCSB. A preliminary trial with one of the group members has been run with encouraging results. Additional UCSB faculty and research groups will be incorporated as the program grows.

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。在这个由化学系实验物理化学计划资助的奖项中，加州大学圣巴巴拉分校的Michael Bowers教授探索了为什么生命系统中的肽和蛋白质只由L-氨基酸组成的问题-生物学中最深的奥秘之一。 Bowers教授和他的学生们将从几个简单的肽模型系统开始，这些肽有各种手性混合形式。 这些肽足够小（5或6个氨基酸长），可以对它们进行良好的理论，以帮助理解观察到的折叠和聚集趋势的变化，作为其手性纯度的函数。这些肽家族还将为该提案的第二个主要目标-淀粉样蛋白形成机制提供入口。 淀粉样蛋白在复杂的生命系统中普遍存在，并与许多严重疾病（阿尔茨海默氏症，2型糖尿病等）有关。 我们的目标是了解聚集过程，以及最初的卷曲或α-螺旋低聚系统如何最终成为大的β-折叠组件。作为这项工作的一部分，鲍尔教授的团队将与柏林弗里茨哈伯研究所的格哈德·梅耶尔和格特·冯·赫尔登开展合作。 这个小组正在建造一个最先进的仪器，以鲍尔教授的规格，这项工作耦合到一个新的自由电子激光器正在建设中的设施。 最后，研究人员已经开始研究一个相关的生物学重要的淀粉样蛋白系统，37个残基的IAPP或胰淀素肽，参与2型糖尿病。 人野生型肽迅速形成大的寡聚体，但许多非常相似的肽不会。 初步数据表明，紧凑的组件导致原纤维形成（因此疾病），而相同的寡聚体数量的细长组件不会进一步聚集。 计划进行建模和进一步的实验，以充分了解这些初步结果。美国的科学教育正处于持续低迷状态，这威胁到我们在创新和技术发展方面的世界领导地位。 这些问题很早就开始了。 五年级被视为儿童科学发展的第一个“去”或“不去”指标。 在UCSB有一个强大的外展计划在5年级水平发起和前组成员与当前的研究小组成员的持续帮助下持续。 鲍尔斯教授决定解决年轻人的第二个“去”或“不去”的决定时间-他们的高中时代。 他的小组正在开发一个外展计划，利用所有小组成员向高中班级介绍他们的研究项目，并讲述他们的个人科学故事以及他们如何在UCSB的研究生院结束。 与小组成员之一进行的初步试验取得了令人鼓舞的结果。 随着项目的发展，UCSB的其他教师和研究小组将被纳入其中。