CAREER: Technologies for Genome-wide In vivo Study of Neuronal (Axonal) Degeneration

0845347M。YanikAxonal变性是发生在神经退行性疾病早期阶段的主要过程。了解轴突变性的分子机制可能会导致许多毁灭性疾病的治疗策略。物理损伤后轴突变性的体内研究在很大程度上限于具有复杂神经系统的生物体，其中难以进行损伤和遗传研究显著限制了分子途径的发现。小动物模型如C.秀丽线虫允许强大的基因操作。本课题研究了C.将利用遗传学、微流控和光学技术对秀丽线虫进行研究。几种突变株将被表征，以了解各种分子途径对轴突变性的影响。将在亚细胞分辨率的物理损伤后进行轴突变性的体内全基因组研究。拟议的研究可以快速发现参与神经退行性变早期阶段的遗传靶点和细胞通路，对基础科学和医学都有潜在影响。与研究部分协同作用，这一建议将使一个实质性的教育和推广计划。教育和研究将通过（1）为学生提供（本科生，硕士和研究生）在麻省理工学院在一个新的和重要的研究领域令人兴奋和宝贵的研究机会，（2）与中学外展计划，以帮助年轻学生开始在科学和技术的职业生涯，（3）试图吸引少数民族学生（特别是非洲裔美国人，美国印第安人，西班牙裔美国人以及其他为麻省理工学院工程学院增添多样性的人）在我们的研究小组工作，（4）将新的研究成果反馈到PI目前正在开发的课程中，以及（5）广泛接触社区。

0845347M. YanikAxonal degeneration is a major process occurring during early stages of neurodegenerative diseases. Understanding molecular mechanisms of axonal degeneration may lead to therapeutic strategies for many devastating diseases. In vivo study of axonal degeneration following physical injury has been largely limited to organisms with complex nervous systems, where difficulty of performing injury and genetic studies is significantly limiting discovery of molecular pathways. Small-animal models like C. elegans allow powerful genetic manipulations. In this project, cellular pathways of axonal degeneration in C. elegans will be studied using genetic, microfluidic and optical technologies. Several mutant strains will be characterized for understanding effects of various molecular pathways on axonal degeneration. In vivo genome-wide studies of axonal degeneration will be conducted following physical injury at sub-cellular resolution. The proposed studies can allow rapid discovery of genetic targets and cellular pathways involved in early stages of neurodegeneration with potential impact on both fundamental science, as well as, medicine. In synergy with the research component, this proposal will enable a substantial educational and outreach program. Education and research will be integrated by (1) providing the students (undergraduate, masters, and graduate) with exciting and valuable research opportunities at MIT in a new and significant research field, (2) working with secondary school outreach programs to help young students start a career in science and technology, (3) trying to attract underrepresented minority students (particularly African Americans, American Indians, Hispanic Americans as well as others who add diversity to MIT's School of Engineering) to work in our research group, (4) feeding new research results back into the courses that the PI is currently developing, and (5) reaching community at large.