CAREER: Genome-wide Approaches to Elucidating the Role of Nonsense-mediated mRNA Decay in Regulating Gene Expression

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Intellectual Merit: Cells have evolved elaborate mechanisms to ensure faithful expression of the genetic material. In cases where DNA copies harbor mutations that lead to expression of incomplete proteins, a quality control strategy distinguishes and rapidly eliminates the aberrant material from the cell. How the cell provides this critical safeguard while maintaining accurate gene expression remains an important unanswered biological question. Using a comprehensive set of emerging scientific technologies, this research will identify and characterize the targets of this quality control pathway in an effort to better understand how this level of protective gene regulation is achieved.Broader Impacts: The research objectives outlined in this project provide an ideal framework to educate, train, and mentor high school, undergraduate and graduate students in critical thinking, scientific method, and hands-on experimental approaches. The development of research skills by junior scientists in the laboratory will be coupled with the launch of an undergraduate course directed at preparing women and minorities pursuing careers in science, engineering and mathematics for academic and institutional challenges they might face and resources available to help maximize success in these fields. Together, these classroom and laboratory opportunities will strengthen the learning and enhance the competitiveness of young scientists at various stages of their training.