Gardner Lab MIRA Proposal: Microtubules and Mitosis

加德纳实验室采用实验和计算相结合的方法， 剖析细胞内微管长度调节的分子机制， 在有丝分裂过程中，力信号是如何确保染色体正确分离的。我们使用 生物物理计算模型，以更好地整合和理解我们的实验 观察，作出新的实验预测，并测试我们提出的细胞 物理机制是合理的。总的来说，我们是一个细胞生物物理实验室， 将细胞生物学工具与生物物理学方法相结合， 微管动力学，并在有丝分裂的力量解剖。实现本报告所述的目标 应用将提供机制的见解如何在微管分子尺度的变化， 结构可以调节微管相关蛋白定位的细胞尺度变化 以及染色体结构和刚度的变化如何影响 有丝分裂期间细胞水平的张力信号。特别是，这一应用将推动我们的 理解：1）微管结构如何改变蛋白质结合，反之亦然，2）如何 细胞在有丝分裂期间读出并响应细微的张力信号，以及3） 疾病过程如癌症可能改变有丝分裂期间的张力信号传导， 非整倍体是癌细胞标志，对着丝粒硬度和张力的影响 有丝分裂时的信号

The Gardner Laboratory uses a combination experimental and computational approach to dissect molecular mechanisms for how microtubule lengths are regulated inside of cells, and for how force signaling acts to ensure proper chromosome segregation during mitosis. We use biophysical computational modeling to better integrate and understand our experimental observations, make new experimental predictions, and to test whether our proposed cellular mechanisms are physically reasonable. Overall, we are a cellular biophysics laboratory that combines cell biology tools with biophysical methods to shed new light on the regulation of microtubule dynamics, and to dissect forces in mitosis. Achieving the goals described in this application will provide mechanistic insights into how molecular-scale changes in microtubule structure could regulate cellular-scale changes in microtubule-associated protein localization and binding, as well as how changes in chromosome structure and stiffness could affect cellular-level tension signaling during mitosis. In particular, this application will advance our understanding of: 1) how microtubule structure can alter protein binding, and vice versa, 2) how the cell reads out and responds to nuanced tension signaling during mitosis, and 3) how a disease process such as cancer may alter tension signaling during mitosis, and the specific impact of aneuploidy, which is a hallmark of cancer cells, on centromere stiffness and tension signaling during mitosis.