CAREER: Cracking the Cleavage Code of RNase Y and Its Associated Y-Complex in Firmicutes

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The objective of this research is to elucidate a cryptic code in bacterial genomes that determines the rate of protein production. This new information will help explain how bacteria utilize genetic information to interact with and change the environment they live in, which in turn could have wide ranging impacts, from fundamental biology to biotechnology. Graduate students participating in the project will learn to develop novel high-throughput measurements and statistical methods for analyzing large-scale data sets. Synergistic with the interdisciplinary nature of the research, the education and outreach components of this project will promote an integrated learning experience in biology and statistics. Both hypothesis-driven research methods and hypothesis-testing statistical concepts will be taught in an interactive format that promotes curiosity-driven inquiry and broadens participation.Messenger RNAs are templates for protein synthesis, and their lifetimes determine the yield of proteins. This research will identify the molecular determinants of the initial cleavage event that leads to RNA degradation in Gram-positive bacteria. Novel genome-wide techniques will be leveraged to reveal different classes of cleavage sites, and commonalities among them will be identified through bioinformatics. This latitudinal investigation will be complemented with two longitudinal studies using deep mutational scanning and phylogenetic analysis of conservation. Furthermore, genome-wide screens will be performed to provide the first comprehensive view of trans-acting factors that regulate RNase activities. A quantitative definition of cleavage codes and their effectors will greatly enhance our understanding of gene expression programs employed by bacteria, and potentially transform our ability to design predictable genetic circuits for synthetic biology.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.