Ryan Flynn of Harvard on Non-Coding RNA

On today’s show, Dr. Ryan Flynn of Harvard Medical School and Boston Children’s Hospital takes us into a newly emerging layer of biology: the architecture of the cell surface itself. Flynn first gained attention for the discovery of glycoRNA — RNA molecules displayed on the outside of cells — a finding that challenged the traditional picture of the cell surface as a world composed primarily of proteins and glycans. RNA has long been understood mainly as a carrier of genetic information (messenger RNA), but Flynn’s work has show that it has other functions critical to basic processes in the cell. As we’ve been hearing on the program, biology has largely been a science of inventory. Throughout today’s conversation, Flynn argues that molecular organization itself may be a fundamental biological variable. Not simply whether a molecule exists, but where it exists, what it is adjacent to. Using technologies such as Pixelgen’s Proximity Network Assay, his lab is beginning to map the “cell surface architecture,” or the arrangement of proteins, glycans, and nucleic acids that together govern signaling and cellular behavior.The implications stretch across biology. Flynn describes early evidence that extracellular RNA can tune classical signaling pathways such as VEGF-mediated angiogenesis by physically modulating how growth factors engage receptors on endothelial cells. Remove the RNA, and growth factor binding changes dramatically. Rather than acting as a simple on/off switch, the RNA appears to function as a finely tuned regulatory layer controlling signaling strength.In cancer, where cell-surface signaling drives growth, invasion, and immune escape, looking at the organization of the cell surface may determine whether therapies can physically access their targets. Flynn points to bispecific antibodies and T-cell engagers as examples of drugs whose function already depends on proximity and molecular arrangement, even if work in biology has not fully measured those variables before. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe