Gardner Lab MIRA Proposal: Microtubules and Mitosis

加德纳实验室使用实验和计算相结合的方法来 剖析微管长度如何在细胞内调节的分子机制，以及 在有丝分裂过程中，强制信号如何起作用以确保适当的染色体分离。我们用 生物物理计算模型，以更好地整合和理解我们的实验 观察，做出新的实验预测，并测试我们提出的细胞 机械装置在物理上是合理的。总体而言，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方法相结合，为调节 微管动力学，并对有丝分裂中的力量进行解剖。实现本文件中描述的目标 应用将提供对微管中分子尺度如何变化的机械性见解 结构可调节微管相关蛋白定位的细胞尺度变化 和结合，以及染色体结构和硬度的变化如何影响 有丝分裂过程中细胞水平的张力信号。特别是，这一应用程序将推进我们的 理解：1)微管结构如何改变蛋白质结合，反之亦然；2)如何 在有丝分裂期间，细胞读出并对细微差别的张力信号做出反应，以及3)如何 疾病过程，如癌症，可能会改变有丝分裂过程中的张力信号，而特定的 作为癌细胞标志的非整倍体对着丝粒僵硬和张力的影响 有丝分裂过程中的信号。

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.