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

智能智能这个项目的目标是使用协同实验和计算模型来回答有关微管细胞骨架的系统级行为的基本问题。微管是重要的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中的一个中心问题。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换。该项目的长期目标是通过将实验与迭代多尺度建模相结合来建立对DI及其通过MT结合蛋白调节的理解。这项研究的具体目标是：1)了解并寻求建立一套关于MT结合蛋白如何以MT+端跟踪蛋白为模型协作调节MT动力学和聚合物质量的一般原则；2)定义本体MT聚合物和单个MT的行为之间的关系。一个关键的目标是使用建模方法来研究和提炼定义MT动力学的平衡聚合物的经典理论。虽然重点放在MT上，但加深的理解应该与其他细胞骨架聚合物相关；3)开发可自由传播的软件包以及相关工具和教学电子教程，以帮助学生和研究人员使用MT组装的计算模型对动态MT系统有一个直观的了解。更广泛的IMPACTS他的项目结合了建模和实验工作，将帮助各级学生和研究人员对动态MT系统有一个直观的了解。这一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显著例子)到控制农业害虫(一些主要的抗寄生虫和抗真菌化合物针对MTS)的应用非常重要。PI将把作为该项目一部分开发的软件工具集成到他们的类中。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方面的跨学科培训。与这项研究有关的项目将纳入圣母大学教师研究经验方案，以及促进少数民族学生研究生和博士学习的方案。

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.