Ryan A. Flynn, MD, PhD
The Flynn lab develops chemical tools to study the interface of RNA biology and glycobiology in the context of cell state transitions and cell-cell communication.
Glycans regulate a myriad of essential cellular functions, especially in the context of cell surface events. For instance, complex glycans facilitate the folding and purposeful trafficking of proteins and lipids for secretion or membrane presentation. Thus, many fundamental processes such as embryogenesis, host-pathogen recognition and tumor-immune interactions rely on proper glycosylation (Reily et al., 2019; Varki and Gagneux, 2015). Glycans are present in every cell studied to date, across the kingdoms of life (Varki and Gagneux, 2015) and in mammals are composed of roughly 10 monomeric carbohydrate units.
In a traditionally adjacent field of study, RNA represents another biopolymer that is central to all known life. While the building blocks of RNA are canonically limited to four bases, post-transcriptional modifications (PTMs) can dramatically expand the chemical diversity of RNA, with >100 PTMs having been identified (Machnicka et al., 2013; Nachtergaele and He, 2016; Frye et al., 2018). It is therefore not surprising that the cellular role for RNA is more complex than that of a simple messenger. For instance, RNAs function as scaffolds, molecular decoys, enzymes, and network regulators across the nucleus and cytosol (Cech and Steitz, 2014; Sharp, 2009; Wang and Chang, 2011). With the exception of a few monosaccharide-based tRNA modifications (Kasai et al., 1976; Okada et al., 1977), there has been so far no evidence of a direct linkage between RNA and glycans in nature.
The Flynn lab studies a biomolecule called glycoRNA, which is a conjugate of sialylated N-glycans produced by the canonical ER/Golgi-lumen biosynthetic machinery and specific mammalian small noncoding RNAs. glycoRNAs exist across every mammalian cell type we have looked in and are present in vivo. Collectively, our initial findings suggest the existence of a previously unknown interface of RNA biology and glycobiology and an expanded role for RNA in extracellular biology. Ongoing work seeks to expand our understanding of the biosynthetic processes, trafficking mechanisms, and functional impact of glycoRNAs in the context of cell fate decisions and cell-cell communications.
Ryan Flynn is an Assistant Professor at the Boston Children’s Hospital in the Stem Cell Program and in the Department of Stem Cell and Regenerative Biology at Harvard University. Ryan graduated from MIT in 2010 and subsequently completed his M.D. and Ph.D. training at Stanford University in 2017. After completing his postdoctoral fellowship also at Stanford, he moved to Harvard to establish his independent laboratory in 2021.