Gardner Lab MIRA Proposal: Microtubules and Mitosis

加德纳实验室 MIRA 提案：微管和有丝分裂

• 批准号: 10405063
• 负责人: Melissa Gardner
• 金额: $ 36.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405063
• 关键词: Affect; Aneuploidy; Binding; Binding Proteins; Biophysics; Cell division; Cells; Cellular biology; Centromere; Chromosome Segregation; Chromosome Structures; Chromosomes; Computer Models; Disease; Ensure; Goals; Laboratories; Length; Light; Link; Malignant Neoplasms; Microscopy; Microtubule-Associated Proteins; Microtubules; Mitosis; Molecular; Process; Prognosis; Regulation; Role; Signal Transduction; Sister; Structure; Testing; Time; biophysical techniques; cancer cell; cancer therapy; daughter cell; insight; molecular scale; tool

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.

加德纳实验室采用实验和计算相结合的方法

项目成果

Centromere Tension Measurement in Budding Yeast Mitosis.

• DOI: 10.1007/978-1-0716-1904-9_15
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)

Straightening up is required to nucleate new microtubules.

• DOI: 10.1083/jcb.202102123
• 发表时间: 2021-04-05
• 期刊: The Journal of cell biology
• 作者: Gardner MK

Manipulation and quantification of microtubule lattice integrity.

微管晶格完整性的操纵和量化。

• DOI: 10.1242/bio.025320
• 发表时间: 2017
• 期刊: Biology open
• 影响因子: 2.4
• 作者: Reid,TaylorA;Coombes,Courtney;Gardner,MelissaK
• 通讯作者: Gardner,MelissaK

Low tension recruits the yeast Aurora B protein Ipl1 to centromeres in metaphase.

• DOI: 10.1242/jcs.261416
• 发表时间: 2023-08-15
• 期刊: Journal of cell science
• 影响因子: 4