Host: Vince Racaniello
Title: Quantitative measurement of the virus life cycle in cancer and the environment
Abstract: My laboratory studies virology at the interface of molecular genetics and infectious disease. The overarching goals significantly impact both basic science (mechanisms of transcriptional regulation) and translational medicine (preclinical cancer therapeutics and wastewater-based epidemiology). My talk will cover two selections from our research program. In the first story, I will describe how we use single-cell transcriptomics to understand the life cycle of individual viruses in cancer. Herpesviruses epigenetically switch between a transcriptionally quiescent latent phase and an actively replicating lytic phase. While the lytic phase comprises of a gradient of gene expression, the latent phase is generally thought of as a single static state. We measured properties that contradict this model with the Kaposi sarcoma-associated herpesvirus in primary effusion lymphoma. Trace lytic RNA can be found in most cells of this population even without reactivation. We also detected precise coordination of RNA levels between two latent genes across orders of magnitude. Our laboratory then targeted this lytic transcription to reduce proliferation in cell culture and animal models. In the second story, I will describe how we use wastewater-based diagnostics to understand the life cycle of a pandemic in individual buildings. We developed an accessible protocol for surveillance of SARS-CoV-2 in dormitory sewage and monitored waves of COVID-19 at Barnard College. We determined a threshold of sensitivity and observed the emergence of variants to inform subsequent public health responses. This effort, consisting of a predominantly undergraduate team, continues to monitor a widening scope of pathogens. Both stories highlight the power of quantitative measurements of nucleic acids in understanding viral growth at scales ranging from single cells to tumors to an entire campus.