BioMaPS: Experimental and Computational Studies of Microtubule Dynamics and Regulation by Binding Proteins

BioMaPS：微管动力学和结合蛋白调节的实验和计算研究

基本信息

批准号：
1244593
负责人：
Holly Goodson
金额：
$ 89.7万
依托单位：
University of Notre Dame
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1244593&HistoricalAwards=false
关键词：
BioMaPS Experimental Computational Studies Microtubule

项目摘要

INTELLECTUAL MERITThe goal of this project is to use coordinated experiment and computational modeling to answer fundamental questions about the system-level behavior of the microtubule cytoskeleton. Microtubules (MTs) are the primary components of crucial subcellular structures including the mitotic spindle, which segregates the chromosomes, and the intracellular transport network, which organizes the cytoplasm. Understanding how MT-based structures assemble, are maintained, and drive cell organization is a central problem in cell biology. MTs exhibit a surprising behavior known as dynamic instability -- individual MT fibers transition randomly between extended phases of growth and depolymerization. The long-term goal of this project is to establish an understanding of DI and its regulation by MT binding proteins by coupling experiment with iterative multi-scale modeling. The specific goals of this research are: 1) Obtain an understanding of, and seek to establish, a set of general principles for how MT binding proteins cooperate to modulate MT dynamics and polymer mass using MT plus-end tracking proteins as a model; 2) Define the relationship between the behavior of the bulk MT polymer and that of individual MTs. A key goal is to use modeling approaches to investigate and refine classical theories of equilibrium polymers that define MT dynamics. While the focus is on MTs, the improved understanding should be relevant to other cytoskeletal polymers; 3) Develop freely disseminated software packages with associated tools and instructional electronic tutorials to help students and researchers gain an intuitive understanding of dynamic MT systems using computational models of MT assembly. BROADER IMPACTSThis projects combined modeling and experimental effort will help students and researchers at all levels gain an intuitive understanding of dynamic MT systems. This understanding is important for applications ranging from nanotechnology (the mitotic spindle is a striking example of a self-organized nanotechnological system) to controlling agricultural pests (some prominent antiparasitic and antifungal compounds are directed at MTs). The PIs will integrate the software tools developed as part of this project into their classes. The project will also educate graduate and undergraduate students who will benefit from interdisciplinary training in biology and computational modeling. Projects related to this research will be incorporated in The Research Experience for Teachers at Notre Dame program as well as into programs promoting graduate and doctoral studies for minority students.

智力价值该项目的目标是使用协调实验和计算模型来回答有关微管细胞骨架系统级行为的基本问题。微管 (MT) 是重要亚细胞结构的主要组成部分，包括分离染色体的有丝分裂纺锤体和组织细胞质的细胞内运输网络。了解基于 MT 的结构如何组装、维持和驱动细胞组织是细胞生物学的一个中心问题。 MT 表现出一种令人惊讶的行为，称为动态不稳定性——单个 MT 纤维在生长和解聚的延长阶段之间随机转变。该项目的长期目标是通过实验与迭代多尺度建模相结合，建立对 DI 及其 MT 结合蛋白调节的理解。本研究的具体目标是： 1) 了解并寻求建立一套关于 MT 结合蛋白如何使用 MT 加端跟踪蛋白作为模型协同调节 MT 动力学和聚合物质量的一般原则； 2) 定义本体 MT 聚合物的行为与单个 MT 的行为之间的关系。一个关键目标是使用建模方法来研究和完善定义 MT 动力学的平衡聚合物的经典理论。虽然重点是 MT，但加深的理解应该与其他细胞骨架聚合物相关； 3) 开发免费传播的软件包以及相关工具和教学电子教程，帮助学生和研究人员使用 MT 组装的计算模型直观地了解动态 MT 系统。更广泛的影响该项目结合了建模和实验工作，将帮助各级学生和研究人员获得对动态机器翻译系统的直观理解。这种理解对于从纳米技术（有丝分裂纺锤体是自组织纳米技术系统的一个引人注目的例子）到控制农业害虫（一些著名的抗寄生虫和抗真菌化合物针对MT）等应用都很重要。 PI 会将作为该项目一部分开发的软件工具集成到他们的课程中。该项目还将教育研究生和本科生，他们将受益于生物学和计算建模的跨学科培训。与这项研究相关的项目将纳入圣母大学教师研究经验项目以及促进少数民族学生研究生和博士研究的项目。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Relationship between dynamic instability of individual microtubules and flux of subunits into and out of polymer

单个微管的动态不稳定性与进出聚合物的亚基通量之间的关系

DOI：
10.1002/cm.21557
发表时间：
2019-09
期刊：
Cytoskeleton
影响因子：
2.9
作者：
Mauro, Ava J.;Jonasson, Erin M.;Goodson, Holly V.
通讯作者：
Goodson, Holly V.

Using STADIA to quantify dynamic instability in microtubules

使用 STADIA 量化微管的动态不稳定性

DOI：
10.1016/bs.mcb.2020.03.002
发表时间：
2020-04
期刊：
Methods in cell biology
影响因子：
0
作者：
Patel, RJ;Murray, KS;Martin, PO;Sinclair, M;Scripture, JP;Goodson, HV;Mahserejian, SM.
通讯作者：
Mahserejian, SM.

Behaviors of individual microtubules and microtubule populations relative to critical concentrations: dynamic instability occurs when critical concentrations are driven apart by nucleotide hydrolysis

个体微管和微管群相对于临界浓度的行为：当临界浓度因核苷酸水解而分开时，会发生动态不稳定

DOI：
10.1091/mbc.e19-02-0101
发表时间：
2020-03
期刊：
Molecular Biology of the Cell
影响因子：
3.3
作者：
Jonasson, Erin M.;Mauro, Ava J.;Li, Chunlei;Labuz, Ellen C.;Mahserejian, Shant M.;Scripture, Jared P.;Gregoretti, Ivan V.;Alber, Mark;Goodson, Holly V.;Mogilner, Ale
通讯作者：
Mogilner, Ale

Microtubules and Microtubule-Associated Proteins

微管和微管相关蛋白