Alpha II-Spectrin: Mechanical Spring and Structural Scaffold for the Nucleoskeleton

Alpha II-Spectrin：核骨架的机械弹簧和结构支架

• 批准号: 1300476
• 负责人: Kris Dahl
• 金额: $ 34.5万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1300476&HistoricalAwards=false
• 关键词: Alpha; II; Spectrin; Mechanical; Spring

The research objective of this award is to determine how opposing mechanical elements of the nucleus help maintain proper shape of the organelle which houses the DNA. The nucleus of mammalian cells has a peripheral network of lamin filaments that provides stiffness. Preliminary results show that alpha II-spectrin provides mechanical resilience or recoil, which may be described as a "spring". Studies conducted under this award will test the mechanisms of this spring hypothesis by quantifying recovery of nuclei in cells under force. The force responsiveness of the lamin network and subnuclear components including the DNA will be observed during mechanical testing in cells that have been depleted of alpha II-spectrin. Also, binding partners will be determined for alpha II-spectrin using purified proteins and protein fragments so that a more accurate description of the architecture can be identified. Although strength and stiffness is important at every level of physiology, mechanical recoil and resilience also plays an important role in maintaining proper homeostasis. Here, the discovery and investigation of alpha II-spectrin as a nuclear mechanical spring will allow a thorough understanding of integrated cellular mechanics and mechanobiology. If successful, these studies will advance the understanding of nuclear structure, gene expression and mechanical responsiveness of cells. Also, results may provide insights into the large number of human diseases and progressive dystrophies associated with lamins and other nuclear structural proteins. The education plan focuses on enhancing ethics training for undergraduate researchers. To directly impact students from underrepresented groups nationally and internationally, advanced online learning initiatives in Anatomy and Physiology are being developed as a supplement for community college education in pre-medicine.

该奖项的研究目标是确定核的相反机械元素如何有助于保持内含DNA的细胞器形状。哺乳动物细胞的细胞核具有可提供刚度的层粘连丝的周围网络。初步结果表明，αII-谱蛋白提供机械弹性或后坐力，这可能被描述为“春季”。根据该奖项进行的研究将通过量化在力下细胞中的细胞中恢复核的恢复来检验本春季假设的机制。在已经耗尽αII-光谱蛋白的细胞中，将观察到在机械测试中观察到层固定网络和核下成分的力响应能力。同样，将使用纯化的蛋白质和蛋白质片段确定结合伴侣为αII-谱蛋白确定结合伴侣，以便可以鉴定出对体系结构的更准确描述。尽管力量和僵硬在每个生理学水平上都很重要，但是机械后坐力和弹性在维持适当的稳态方面也起着重要作用。在这里，将αII-光谱蛋白作为核力学弹簧的发现和研究将允许对整合的细胞力学和机械生物学有透彻的了解。如果成功，这些研究将提高对核结构，基因表达和细胞机械反应性的理解。此外，结果可能会提供有关与层粘连蛋白和其他核结构蛋白相关的大量人类疾病和进行性营养不良的见解。教育计划着重于增强本科研究人员的道德培训。为了直接影响全国和国际上代表性不足的群体的学生，正在开发解剖学和生理学的先进在线学习计划，以作为医学前社区大学教育的补充。