Michael Mingroni

I am a postdoc applying my enzymology background in the world of flaviviruses. I am currently working toward uncovering the capping mechanism of the NS5 enzyme in West Nile virus. My project mixes biochemical approaches, structural biology, and virology to better understand the WNV NS5 enzymatic capping mechanism of viral RNA, and the critical interactions involved in viral replication. Flaviviral RNA capping involves the installation of the m7GpppA onto the 5’ end of the positive strand RNA, enabling newly synthesized RNA to evade detection from the host antiviral response in its journey to be packaged into virions or to continue infection through the translation of more viral proteins. The NS5 enzyme contains the guanylyltransferase, methyltransferase, and RNA-dependent RNA polymerase, therefore understanding substrate interactions is crucial to developing inhibitors and therapeutics against flaviviral infections. Using site-directed mutagenesis, we are characterizing the guanylyltransferase active site by discovering important residues in GTP capping kinetics through the development of in vitro biochemical assays, as well as observing in vivo effects of NS5 variants on viral replication through infectious assays. I grew up just south of Denver, before earning my B.S. in Chemistry at the University of Northern Colorado in 2012. I attended the University of Massachusetts Amherst and earned my M.S. in Chemistry in 2017, and my Ph.D. in 2021 under the advisement of Dr. Mike Knapp. My thesis focus was in biochemistry and enzymology, and understanding the catalytic mechanism of the oxygen sensing enzyme, FIH-1, using isotopic probes to isolate and study kinetic effects on individual chemical steps. I am excited to be in the field of flaviviruses and am interested in developing RNA probes using chemical biology to learn more about the higher ordered structures of the 3’-UTR, and their roles in infection. I have a huge passion for teaching, and hope to continue my career in academia. I am thrilled to be back in the state of Colorado, as I enjoy being outdoors, and trying new breweries. I like hiking, camping, paddleboarding, and have enlisted myself in (and suffered through) a few half marathons. While in Massachusetts, I was on a bar trivia team named Tubby Taft, and is likely the most competitive I’ve ever been.