Actin Assembly and Cell Motility: Mechanisms and Regulation

肌动蛋白组装和细胞运动：机制和调节

基本信息

批准号：
9252484
负责人：
JOHN A COOPER
金额：
$ 50.94万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Our lab studies molecular and cellular mechanisms for actin assembly and actin-based cell motility. We want to understand how actin filaments assemble, how they interact with other cytoskeletal components and membranes, and how these interactions dictate cell shape and movement. The MIRA goals are: 1) combining existing grants, 2) promoting flexibility in new research directions, and 3) promoting stability and mentoring. 1) Existing Grants. "Mechanisms for Transendothelial Migration" is the current title of a long-standing grant focused on actin assembly and membranes. Transendothelial migration is a new area for us, one that emerged from studies on how NK cells migrate, find and kill their target cells. We are interested in how immune and cancer cells cross the endothelium of the vasculature during physiological and pathological processes. The migrating cell and the endothelial cell both actively participate, changing shape and exerting force as a result of actin filaments interacting with the plasma membrane and intracellular membranous organelles. "Regulation of Actin Capping Protein" is the current title of a newer grant focused on novel mechanisms of regulation of actin capping protein. Capping protein is a key regulator of the availability and activity of actin- filament barbed ends. Recent discoveries of novel regulators of capping protein have revealed unexpected insights that dramatically change our view of actin assembly in cells. We now know that regulators target capping protein to sites where cells need to assemble actin filaments and that they tune its filament-capping activity to a level that is physiologically relevant for the concentrations of the reactants and kinetics of the reactions. 2) Flexibility and New Research Directions. I have been successful in pursuing new directions, using new experimental systems, and adapting to new technologies, as described in my Biosketch. New areas for our lab in this proposal include novel connections between cytoskeleton filament systems, the use of zebrafish as a vertebrate model system, light-induced control of protein activity, and super-resolution correlative light and electron microscopy. 3) Mentoring and Stability. The MIRA FAQ mentions "more time for conduct of research and mentoring junior scientists in a more stable environment," which resonates strongly with me. I enjoy serving as a mentor, and I am very proud of the success of our lab trainees and my faculty colleagues, within and outside of our department. In terms of stability, while we are grateful for our success in securing continued funding for our research, our ability to make transitions and explore new directions will be made more facile and efficient by the MIRA mechanism.

描述（由申请人提供）：我们的实验室研究肌动蛋白组装和基于肌动蛋白的细胞运动的分子和细胞机制，我们希望了解肌动蛋白丝如何组装，它们如何与其他细胞骨架成分和膜相互作用，以及这些相互作用如何决定细胞形状。 MIRA 的目标是：1) 结合现有的资助，2) 促进新研究方向的灵活性，以及 3) 促进稳定性和指导 1) 现有的资助“机制。跨内皮迁移”是一项专注于肌动蛋白组装和膜的长期资助的当前标题。跨内皮迁移对我们来说是一个新领域，它是从 NK 细胞如何迁移、发现和杀死其靶细胞的研究中出现的。我们正在对免疫细胞和癌细胞在生理和病理过程中如何穿过血管内皮感兴趣。迁移细胞和内皮细胞都积极参与，由于肌动蛋白而改变形状并施加力量。 “肌动蛋白帽蛋白的调节”是一项新资助的当前标题，重点关注肌动蛋白帽蛋白的新调节机制，是肌动蛋白可用性和活性的关键调节剂。 - 新型调节器的最新发现。帽蛋白揭示了意想不到的见解，极大地改变了我们对细胞中肌动蛋白组装的看法。我们现在知道，调节剂将帽蛋白定位到细胞需要组装肌动蛋白丝的位点，并将其丝帽活性调整到生理相关的水平。反应物的浓度和反应动力学2)。灵活性和新的研究方向。正如我的 Biosketch 中所述，我成功地追求了新的方向，使用了新的实验系统，并适应了新技术。我们实验室的新领域包括细胞骨架丝系统之间的新连接、使用。斑马鱼作为脊椎动物模型系统、光诱导的蛋白质活性控制以及超分辨率相关光学和电子显微镜 3) MIRA 常见问题解答提到“更多时间”。 “在更稳定的环境中进行研究和指导初级科学家”，这与我产生了强烈的共鸣。我喜欢担任导师，并且我为我们的实验室实习生和我的教职同事在我们内部和外部的成功感到非常自豪在稳定性方面，虽然我们感谢我们成功地为我们的研究获得了持续的资金，但 MIRA 机制将使我们的转型和探索新方向的能力变得更加轻松和高效。