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

0845347M。神经轴突变性是发生在神经退行性疾病早期的一个主要过程。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局限于具有复杂神经系统的生物体，在这些生物中，进行损伤和遗传学研究的难度大大限制了对分子通路的发现。像线虫这样的小动物模型可以进行强大的基因操作。在这个项目中，将使用遗传学、微流体和光学技术来研究线虫轴突退化的细胞路径。将对几个突变菌株进行特征描述，以了解不同分子途径对轴突变性的影响。在体内轴突变性的全基因组研究将在物理损伤后以亚细胞分辨率进行。拟议的研究可以快速发现神经退化早期阶段涉及的遗传靶点和细胞路径，这可能会对基础科学和医学产生影响。在与研究部分的协同作用下，这项提议将实现一个实质性的教育和推广方案。教育和研究将通过以下方式整合：(1)在麻省理工学院为学生(本科生、硕士和研究生)在一个新的重要研究领域提供令人兴奋和宝贵的研究机会，(2)与中学外展项目合作，帮助年轻学生在科学和技术领域开始职业生涯，(3)努力吸引未被充分代表的少数族裔学生(特别是非裔美国人、美国印第安人、西班牙裔美国人以及其他增加麻省理工学院工程学院多样性的人)加入我们的研究小组，(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)接触到广大社区。

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.