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

该奖项的研究目标是确定细胞核中相反的机械元素如何帮助维持容纳DNA的细胞器的适当形状。哺乳动物细胞的细胞核有一个提供刚性的核纤丝的外围网络。初步结果表明，α ii -谱蛋白提供机械弹性或后坐力，这可能被描述为“弹簧”。在该奖项下进行的研究将通过量化在受力下细胞中细胞核的恢复来测试这个春季假说的机制。层粘连蛋白网络和包括DNA在内的亚核组分的力响应性将在耗尽α ii -谱蛋白的细胞中进行机械测试时观察到。此外，将使用纯化的蛋白质和蛋白质片段确定α II-spectrin的结合伙伴，以便更准确地描述其结构。虽然强度和刚度在生理学的各个层面都很重要，但机械反冲和弹性在维持适当的体内平衡方面也起着重要作用。在这里，α ii -谱蛋白作为核机械弹簧的发现和研究将使我们对细胞力学和力学生物学的综合理解更加透彻。如果成功，这些研究将促进对细胞核结构、基因表达和细胞机械反应的理解。此外，该结果可能为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提供见解。该教育计划的重点是加强对本科生研究人员的道德培训。为了直接影响国内和国际上代表性不足群体的学生，正在开发解剖学和生理学高级在线学习计划，作为社区大学医学预科教育的补充。

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.