RUI: Probing Early Events in Amyloid-beta Association by Single-Pair Forster Resonance Energy Transfer

RUI：通过单对福斯特共振能量转移探索淀粉样蛋白-β 关联的早期事件

• 批准号: 0848824
• 负责人: Robin Lammi
• 金额: $ 25.13万
• 依托单位: Winthrop University
• 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: 2009-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0848824&HistoricalAwards=false
• 关键词: RUI; Probing; Early; Events; Amyloid

In this project, funded by the Experimental Physical Chemistry Program of the Division of Chemistry, Robin Lammi and undergraduate researchers at Winthrop University will investigate structural heterogeneity in dimers of amyloid-β peptide (Aβ). Small oligomers of this protein are closely linked to neurodegeneration in Alzheimer?s disease and likely serve as critical nuclei in the growth of ordered fibrils used as nanowires and sensors. By performing single-pair Förster resonance energy transfer (spFRET) measurements on dozens of localized, fluorescently labeled dimers, one at a time, Lammi and her students will directly probe the oligomer-to-oligomer variation obscured in bulk-solution measurements, gaining unique, molecular-level insight into persistent versus transient dimer structures. In addition to affording new empirical insights into the earliest steps in Aβ association, this project will permit intense, interdisciplinary training of undergraduate researchers. The inclusion of a single-oligomer laboratory experiment and the introduction of project-derived data and analysis techniques in the undergraduate curriculum will bring advanced research methods into the classroom, impacting all chemistry majors at Winthrop, including many students from underrepresented groups.

在这个由化学系实验物理化学项目资助的项目中，罗宾·拉米和温斯罗普大学的本科生研究人员将研究淀粉样多肽(A&A；)二聚体的结构异质性。这种蛋白的小寡聚体与阿尔茨海默病-S病的神经退行性变密切相关，可能是用作纳米线和传感器的有序纤维生长的关键核。通过对数十个局部荧光标记的二聚体逐一进行单对Förster共振能量转移(SpFRET)测量，Lammi和她的学生将直接探测本体溶液测量中隐藏的低聚物到低聚物的差异，从而获得独特的、分子水平的持久和瞬时二聚体结构洞察。除了对A&A；协会最早的步骤提供新的经验性见解外，该项目还将允许对本科生研究人员进行密集的、跨学科的培训。在本科课程中加入单一低聚物实验室实验，并将项目衍生数据和分析技术引入课堂，将把先进的研究方法带入课堂，影响到温斯罗普所有化学专业的学生，包括许多来自代表性不足群体的学生。