This proposal describes a research and training plan that is designed to enhance the career development of Dr. Erich G. Chapman.
The research aims of this proposal revolve around a series of RNA structures recently discovered within the genomes of different positive-sense RNA viruses. These RNA structures allow portions of these viral genomes to resist or evade the major 5' to 3' and 3' to 5' RNA decay pathways that exist in eukaryotic cells. This leads to a drastic lengthening of the cellular lifetimes of co-transcribed viral RNAs and their high-level accumulation during viral infection. Several lines of evidence suggest that these different RNA stability elements are capable of operating outside of their contexts in different viral genomes. Research described in this proposal will test this hypothesis by transplanting several different viral RNA structures into messenger RNA reporter systems in the model organism S. cerevisiae. Experiments will be conducted to verify their operation and quantify any extensions in cellular RNA lifetimes. These investigations will preface Dr. Chapman's long-term research plans regarding the regulation of RNA metabolism in eukaryotic cells. The career development goals of this proposal are designed to train Dr. Chapman in yeast biology and genomic techniques and to facilitate his transition to an independent academic career. The laboratory skills that Dr. Chapman will develop will build upon his expertise in RNA biochemistry and round out the skill set that he will need as a long-term NIH funded investigator. The training plan that Dr. Chapman will pursue en route to an independent faculty position will include mentoring by Prof. Jeffery S. Kieft, an accomplished HHMI Early Career Scientist and leader in several fields of RNA-related research. Under Dr. Kieft's guidance, Dr. Chapman will engage in a variety of career development activities including mentoring junior scientists, publishing his work in scientific journals, training in the responsible conduct of research, grant-writing, and entry onto the academic job market. Together these activities will enhance Dr. Chapman's skill set and propel him into the successful launch of an independent academic career.

Public Health Relevance

This proposal describes a research and training plan aimed at understanding the ability of viral RNA structures to resist and evade the major RNA-decay pathways that exist within eukaryotic cells. This plan includes using viral RNA structures to artificially extend the lifetime of messenger RNAs in the model organism S. cerevisiae. Together these aims will result in the creation of new research tools and insights into recently discovered and medically relevant biological pathways.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Bender, Michael T
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University of Denver
Schools of Arts and Sciences
United States
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MacFadden, Andrea; O'Donoghue, Zoe; Silva, Patricia A G C et al. (2018) Mechanism and structural diversity of exoribonuclease-resistant RNA structures in flaviviral RNAs. Nat Commun 9:119