CAREER: Investigating Abl Kinase Signaling Pathways that Regulate Actin Dynamics during Development

该奖项是根据2009年美国复苏和再投资法案(公法111-5)资助的。在发育过程中将细胞组织成组织和器官是一个高度监管的过程，需要协调细胞形状变化和细胞迁移。这些细胞行为是由肌动蛋白细胞骨架的重排决定的。Abelson(Abl)激酶是向肌动蛋白细胞骨架传递重排信号的关键分子，但Abl在动物发育过程中从细胞表面接收信号并重塑肌动蛋白的机制尚不清楚。这个项目的总体目标是描述ABL用来调节细胞迁移和体内其他基于肌动蛋白的过程的分子途径。表达激活Abl的果蝇胚胎为在生物体中阐明Abl信号通路提供了一个理想的模型系统，因为激活的Abl改变细胞迁移并导致胚胎发育的明显缺陷。这项研究计划旨在探索候选基因的功能，并确定在体内调节细胞迁移的ABL信号通路的新组件。这些研究将为调节个体细胞在发育过程中行为的分子途径提供重要的见解。广泛的影响。这项研究将与本科和高中阶段的年轻科学家的培训和指导相结合。该项目的总体目标是为更多的年轻科学家提供实践研究培训，并激励这些学生追求基础研究事业。科学培训将纳入本科水平，为独立研究项目提供更多机会，并将这一研究计划的各个方面整合到伦道夫-梅肯学院遗传学的实验室部分，遗传学是一门核心生物学课程。该项目还旨在为当地高中生和高中生物教师提供独特的探究式体验，他们将以团队形式研究Abl信号通路在细胞迁移中的各个方面。在职业生涯早期进行原创性研究的机会将挑战并激励学生进行更多的科学培训。为了接触到更广泛的社区，生物教师将制定一项计划，将他们在这个研究项目中基于探究的经验直接转化为他们高中的科学课程。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Intellectual Merit Organization of cells into tissues and organs during development is a highly regulated process that requires coordinated cell shape changes and cell migration. These cell behaviors are directed by rearrangements of the actin cytoskeleton. Abelson (Abl) kinases are key players in relaying signals for rearrangement to the actin cytoskeleton, but the mechanisms by which Abl receives signals from the cell surface and remodels actin during animal development remain unknown. The overall goal of this project is to characterize the molecular pathways that Abl uses to regulate cell migration and other actin-based processes in vivo. Drosophila embryos expressing activated Abl provide an ideal model system to elucidate Abl signaling pathways in the context of an organism, since activated Abl alters cell migration and leads to visible defects in embryonic development. This research program aims to both explore the functions of candidate genes and identify new components of the Abl signaling pathways that modulate cell migration in vivo. These studies will provide significant insights into the molecular pathways that regulate behaviors of individual cells during developmental processes.Broader Impact.This research will be integrated with the training and mentoring of young scientists at both the undergraduate and high school levels. The overall goals of this program are to provide more young scientists with hands-on research training and to inspire these students to pursue careers in basic research. Scientific training will be incorporated at the undergraduate level by providing additional opportunities for independent research projects and by integrating aspects of this research program into the laboratory component of Genetics, a core biology course, at Randolph-Macon College. This project also aims to provide unique inquiry-based experiences to local high school students and high school biology teachers, who will work as teams to investigate aspects of Abl signaling pathways in cell migration. Opportunities to do original research early in their careers will both challenge and motivate students to pursue additional scientific training. To reach a broader community, the biology teachers will develop a plan for directly translating their inquiry-based experiences in this research program to their high school science courses.