PRFB Fellowship: Effects of metabolic changes on mitotic spindle morphology and chromosome segregation
This research will pursue a fundamental understanding of the relationship between mitochondrial metabolism and chromosome segregation in C. elegans oocytes. Metabolic activity, spindle morphology, and chromosome segregation errors (CSEs) in oocytes will be simultaneously characterized in order to understand the extent to which mitochondrial metabolism determines spindle function and chromosome segregation. The project will employ two broad thrusts. First, biochemical perturbations to metabolic function will be performed and their effects on both spindle morphology and CSE rates will be characterized. The latter goal is to explore the statistical relationship between metabolic activity and spindle morphology/CSE rates in a natural context. This will entail high-throughput measurements of metabolic levels, spindle properties, and CSEs in C. elegans of diverse genetic backgrounds.
Working in an interdisciplinary laboratory, the fellow will deepen his biological understanding and have the opportunity to work with live cells. He will also gain experience with high-value genetics techniques such as RNA interference and quantitative trait loci mapping across varying genetic lines. To quantify metabolite levels in perturbed oocytes, the fellow will also receive training in mass spectrometry at the Small Molecule Mass Spectrometry Facility at the Harvard FAS Center for Systems Biology. In conjunction with this research, the fellow will conduct a carefully tailored outreach program through Fourth Presbyterian Church in South Boston. This highly active urban ministry provides programs and services for neighborhood youths of disproportionately minority and economically challenged backgrounds. Here, the fellow will provide demonstrations, lessons, and active learning in the form of hands-on experiments in a series of 8 weekly classes to run on a yearly basis.