2020 Winner: Investigating Regulation of Nonsense-Mediated Decay During the Inflammatory Response

Project Information
Investigating Regulation of Nonsense-Mediated Decay During the Inflammatory Response
Biomolecular Engineering
Chronic inflammatory diseases affect millions of patients across the world and occur when normal inflammatory pathways become dysregulated. In order to understand more about the regulatory mechanisms that govern innate immunity and how they may become dysregulated in the context of chronic inflammation, I am computationally investigating the regulation of nonsense-mediated decay during the mouse macrophage inflammatory response. The regulation of nonsense-mediated decay has not been studied in innate immunity despite recent observations that show nonsense-mediated decay as an important regulatory process across many different cellular systems. By analyzing whole-cell RNA sequencing data from both short-read and long-read sequences, I determined that transcripts that should normally be targeted by nonsense-mediated decay are enriched post-inflammation, a phenomenon that is unexpected if nonsense-mediated decay is active. Future studies for this project will involve analyzing polysome profiling data to understand changes in translational efficiency of transcripts and expected nonsense-mediated decay targets. This will determine if the normal nonsense-mediated decay pathway is being inhibited during the inflammatory response and allowing for translation of these isoforms. This study may work to identify a potentially important aspect of regulation in the mammalian immune response and provide direction for further studies in understanding transcriptional and translational control of inflammation.
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  • Matthew Arthur Cattle (Cowell)