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

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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.