Collaborative Research: Mechanics of the Cell Nucleus Lipid Bilayers

合作研究：细胞核脂质双层的力学

• 批准号: 1437395
• 负责人: Tanmay Lele
• 金额: $ 15.53万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1437395&HistoricalAwards=false
• 关键词: Collaborative; Research; Mechanics; Cell; Nucleus

The cell nuclear envelope is the physical barrier between the cytoplasm and the nucleus. The envelope regulates gene expression by allowing the access of proteins to DNA through passageways called nuclear pores. The nuclear envelope is unique in that it has two lipid bilayers (not one as is the case with cell membranes). The bilayers are maintained at a regular (and large) distance of nearly 45 nm. How these two bilayers are maintained at that regular spacing, and how they fuse together to form nuclear pores are current open questions in biology; this award is focused on answering these questions. By discovering an explanation for protein-mediated control of bilayer separation, this research will ultimately help develop new strategies for treating diseases that have been linked to mutations in the nuclear envelope proteins. The research program will provide opportunities to recruit outstanding students from underrepresented groups at the University of Houston (UH) and the University of Florida (UF). The findings of the research will be disseminated through journal publications, conference presentations and graduate and undergraduate courses at UH and UF.The award will promote a collaborative partnership between investigators involving experiments, modeling and simulations to elucidate the fundamental physics that underlies nuclear lipid bilayer structure. The experimental work will discover how SUN proteins, which are conserved across different eukaryotic cell types and link the nucleus to the cytoskeleton maintain lipid bilayer structure and integrity. Theoretical work will seek to interpret the experimental findings in the framework of continuum mechanics, by computing the energetics of bilayer separation and fusion. The numerical and experimental findings will be used together to explain the mechanism of bilayer separation.

细胞核膜是细胞质和细胞核之间的物理屏障。包膜通过允许蛋白质通过称为核孔的通道进入DNA来调节基因表达。核膜的独特之处在于它有两个脂质双层（而不是像细胞膜那样只有一个）。双分子层保持在近45 nm的规则（和大）距离。这两个双层是如何保持在这种规则的间距，以及它们如何融合在一起形成核孔是目前生物学中的开放问题;这个奖项的重点是回答这些问题。通过发现蛋白质介导的双层分离控制的解释，这项研究最终将有助于开发治疗与核膜蛋白突变有关的疾病的新策略。该研究计划将提供机会，从休斯顿大学（UH）和佛罗里达大学（UF）的代表性不足的群体招募优秀学生。该研究成果将通过期刊出版物、会议演讲以及UH和UF的研究生和本科生课程进行传播。该奖项将促进研究人员之间的合作伙伴关系，涉及实验、建模和模拟，以阐明核脂双层结构的基础物理学。实验工作将发现SUN蛋白如何在不同的真核细胞类型中保守，并将细胞核与细胞骨架连接起来，以维持脂质双层结构和完整性。理论工作将试图解释实验结果的连续介质力学的框架内，通过计算双层分离和融合的能量。数值计算和实验结果将被用来解释双层分离的机制。