Collaborative Research: Supramolecular Multi-Component Peptide Nanofibrils: Bridging Understanding at Atomic and Mesoscopic Scales with Structure and Theory
合作研究:超分子多组分肽纳米纤维:通过结构和理论在原子和介观尺度上架起理解桥梁
基本信息
- 批准号:2304852
- 负责人:
- 金额:$ 40万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
With the support of the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Bradley L. Nilsson of the University of Rochester, Cristiano Dias of the New Jersey Institute of Technology (NJIT), and Edward Egelman of the University of Virginia will study the supramolecular self-assembly of peptides into nanofibril biomaterials. Peptides are naturally occurring molecules found in all organisms that perform important biological functions, including acting as signaling hormones, including such bioactive peptides as insulin and oxytocin. Peptides can adopt different conformations that influence how they interact with each other. Beta-sheets are one common peptide structural motif. Peptides that assume beta-sheet conformations often rapidly self-assemble into nanofibrils. Some of these nanofibril assemblies are associated with protein misfolding disorders like Alzheimer’s disease and others have been designed to be functional biomaterials. In this work, the team will study how these peptides the co-assemble into these structures. Novel beta-sheet materials, “rippled” beta-sheets, that are distinct from the “pleated” beta-sheets found in nature, will be studied using experimental and computational techniques. These efforts will provide critical insight into the structure of both natural and artificial beta-sheets and the molecular-scale interactions that dictate the assembly of these materials. This research is directed at opening up new avenues for the design of next generation peptide-based nanomaterials. Outreach activity associated with this work includes an inquiry based mini-course on hydrogels called “The Science of Slime” which will be conducted at the participating institutions for pre-university students from grades 7-12. Additionally, the research teams will host high school interns for six weeks during the summer to provide mentoring and increase exposure to scientific research and to the chemical sciences, in general.Under this award the collaborative Rochester, NJIT, Virginia team will investigate the supramolecular assembly of beta-sheet nanofibrils composed of mirror-image peptides by determining the structure of these systems with near-atomic precision and by using computer simulations to investigate the forces driving the formation of these assemblies. This work is directed at the rational design of rippled beta-sheet nanofibril systems. In the first objective, cryo-electron microscopy will be used to elucidate the structure of related pleated and rippled beta-sheet assemblies and complementary computational analyses will be used to rationalize their mechanisms of assembly. In the second objective, computational methods will be used to predict and design novel self-assembled beta-sheet peptide materials and these predictions will be tested experimentally. The results of the experiments will be used to validate and improve predictive computations. This work aims to provide key knowledge regarding the molecular basis for peptide self-assembly processes that will be relevant to understanding protein misfolding processes and for the design of biomaterials with potential applications in energy science and biomedicine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
在化学部的大分子,超分子和纳米化学计划的支持下,罗切斯特大学的布拉德利·L·尼尔森(Bradley L. Nilsson),新泽西州科技研究所的克里斯蒂安诺·迪亚斯(Cristiano Dias),弗吉尼亚大学的爱德华·埃格曼(Edward Egelman)和弗吉尼亚大学的爱德华·埃格曼(Edward Egelman肽是在所有执行重要生物学功能的生物体中发现的天然分子,包括充当信号恐怖剂,包括胰岛素和催产素等生物活性肽。肽可以采用不同的成分,以影响它们之间的相互作用。 β片是一个常见的胡椒结构图案。假设β-构象构象的肽通常会迅速自我组装成纳米纤维。这些纳米纤维组件中的一些与蛋白质错误折叠障碍有关,例如阿尔茨海默氏病,而另一些则被设计为功能性生物材料。在这项工作中,团队将研究这些工作如何将共同组装成这些结构。新型的beta表材料“波纹” beta表与自然界中的“百褶”β片不同,它将使用实验和计算技术研究。这些努力将为自然和人工β表的结构以及决定这些材料组装的分子尺度相互作用提供批判性见解。这项研究旨在为设计基于下一代肽的纳米材料的设计开辟新的途径。与这项工作相关的外展活动包括基于询问的小型水凝胶,称为“粘液科学”,该课程将在参与的机构为7 - 12年级的大学前学生提供。此外,研究团队将在夏季在夏季举办高中实习生六个星期,以增加对科学研究和化学科学的接触,总的来说。在此奖项之后,授予弗吉尼亚州NJIT合作的罗切斯特(NJIT),将调查超分子的超分子组装,并通过确定这些镜像型固定型的镜头纳米纤维来构成这些系统,并通过这些系统来确定这些系统,并通过这些系统来确定这些系统,这些系统与这些系统相关的系统构成了这些系统,并将这些系统构成。驱动这些组件的形成。这项工作针对波纹β-片纳米纤维系统的合理设计。在第一个目标中,冷冻电子显微镜将用于阐明相关的褶皱和波纹β片组件的结构,并且将使用完整的计算分析来合理化其组装机制。在第二个目标中,计算方法将用于预测和设计新型的自组装β-β肽材料,这些预测将经过实验测试。实验的结果将用于验证和改善预测性计算。这项工作旨在提供有关肽自组装过程的分子基础的关键知识,这些过程将与理解蛋白质错误折叠过程以及具有潜在应用在能源科学和生物医学中应用的生物材料设计有关。这奖反映了NSF的法定任务,并通过对基础的智力进行了评估,以评估良好的评估和广泛的效果,以评估为您而言是宝贵的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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Bradley Nilsson其他文献
Bradley Nilsson的其他文献
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{{ truncateString('Bradley Nilsson', 18)}}的其他基金
Collaborative Research: Comparative Studies of Pleated beta-Sheet and Rippled beta-Sheet Peptide Nanofibrils
合作研究:褶皱β-片层和波纹β-片层肽纳米原纤维的比较研究
- 批准号:
1904528 - 财政年份:2019
- 资助金额:
$ 40万 - 项目类别:
Standard Grant
CAREER: Amyloid-Inspired Self-Assembled Hydrogel Materials for Cell Culture Applications
职业:用于细胞培养应用的淀粉样蛋白自组装水凝胶材料
- 批准号:
1148836 - 财政年份:2012
- 资助金额:
$ 40万 - 项目类别:
Continuing Grant
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Collaborative Research: Supramolecular Multi-Component Peptide Nanofibrils: Bridging Understanding at Atomic and Mesoscopic Scales with Structure and Theory
合作研究:超分子多组分肽纳米纤维:通过结构和理论在原子和介观尺度上架起理解桥梁
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