Early Chemotactic Signaling Mediated by an Unconventional Myosin

化学趋向性是一个非凡的过程——环境中少量的化学线索可以引导细胞或生物体向源头运动，就像新鲜出炉的面包的气味吸引我们进入厨房一样。我们工作的目标是利用一个简单的模型系统来了解趋化的基本机制，这个模型系统是社会性变形虫盘基骨柱。从变形虫到人类的趋化途径是高度保守的，所以我们从变形虫身上学到的东西可以让我们了解各种各样的生物的趋化性。在Dictyostelium中发现了一个名为MyoG的趋化途径的新参与者。MyoG是肌凝蛋白家族的一员，肌凝蛋白起着分子马达的作用，在细胞内产生运动。我们的目标是确定MyoG在将细胞外的信号传递到细胞内部负责指导细胞运动的机制中的作用。确定MyoG在趋化途径中的作用方式和位置，以及确定它与哪些其他蛋白质协同作用，将为趋化途径提供新的信息。我们还将在哺乳动物细胞中寻找类似的蛋白质，作为了解趋化性的基本机制以及它如何在数百万年的进化中如此高度保守的第一步。更广泛的影响：拟议的项目将用于向各级学生（从高中到研究生院）介绍基本的研究方法和实践。年轻的学生将与PI在几个子项目上进行一对一的工作，这些子项目是根据每个学生的才能量身定制的。每个学生都将学习科学的方法，鼓励他们思考和回答自己的问题，提出新的问题，并随着项目的进行总结结果。PI积极参与基于趋化性项目的拉丁美洲细胞生物学和生物化学国际培训课程的讲座和实验室模块的开发。这些课程的目标是促进美国和南美学生和研究人员之间的互动和关系。最后，一个关于肌凝蛋白超家族信息的中央网络资源，即肌凝蛋白主页，将被采用、更新和维护。它将为学生和非肌凝蛋白研究人员提供一个全面的资源，以获得有关大肌凝蛋白超家族分子马达单个成员功能的基本信息。

Chemotaxis is a remarkable process -- a small amount of a chemical cue in the environment can direct a cell or organism movement towards the source, like the smell of freshly baked bread draws us into the kitchen. The goal of our work is to understand the basic mechanism of chemotaxis using a simple model system for our studies, the social amoeba Dictyostelium. The chemotaxis pathway is highly conserved from amoebae to humans so what we learn from the amoebae can teach us about chemotaxis is a wide variety of organisms. A new player in the chemotaxis pathway named MyoG has been identified in Dictyostelium. MyoG is a member of a family of proteins called myosins that work as molecular motors, generating movements within cells. Our objective is to determine the role of MyoG in transmitting signals from outside of the cell to the machinery inside that is responsible for directing cell movement. Determining how and where MyoG acts in the chemotaxis pathway and identifying what other proteins it works in concert with will provide new information about the chemotaxis pathway. We will also search for similar proteins in mammalian cells as a first step towards understanding the fundamental mechanism of chemotaxis and how it has been so highly conserved through millions of years of evolution.Broader Impacts: The proposed project will be used to introduce students at all levels (from high school through graduate school) to basic research methods and practice. Young students will work one-on-one with the PI on several subprojects specifically tailored to each student's talents. Each student will be taught scientific methods, encouraged to think through and answer their own questions, formulate new questions, and summarize results as the project proceeds. The PI actively participates in the development of lectures and laboratory modules for International Training Courses in Cell Biology & Biochemistry in Latin America based on the chemotaxis project. The goal of these courses is to foster interactions and relationships between US and South American students and investigators. Finally, a central web resource for information about the myosin superfamily, the Myosin Home Page, will be adopted, updated and maintained. It will serve as a comprehensive resource for students and non-myosin researchers to gain basic information about the function of individual members of the large myosin superfamily of molecular motors.