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

这个项目的目标是使用协调实验和计算建模来回答有关微管细胞骨架的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核心问题。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扩展阶段之间随机过渡。本项目的长期目标是通过耦合实验和迭代多尺度模型建立对DI及其由MT结合蛋白调节的理解。本研究的具体目标是：1）获得的理解，并寻求建立，一套一般原则，为MT结合蛋白如何合作，以调节MT动力学和聚合物质量使用MT加末端跟踪蛋白作为一个模型; 2）定义之间的关系，散装MT聚合物的行为和个别MT。一个关键的目标是使用建模方法来研究和完善经典理论的平衡聚合物，定义MT动力学。虽然重点是MT，提高理解应该是相关的其他细胞骨架聚合物; 3）开发免费传播的软件包与相关的工具和教学电子教程，以帮助学生和研究人员获得一个直观的了解动态MT系统使用MT组装的计算模型。 更广泛的影响这个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MT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突出例子）到控制农业害虫（一些突出的抗寄生虫和抗真菌化合物针对MT）的应用都很重要。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被纳入圣母大学教师的研究经验计划，以及促进少数民族学生研究生和博士研究的计划。

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.