Molecular mechanisms of cell entry, evolution and innate immune recognition of enveloped RNA viruses
Our overarching goal is to gain a mechanistic understanding at the molecular level of how important pathogens interact with their host cells during infection. We seek to understand the following major questions: (1) How do enveloped viruses assemble and recognize host cells? (2) How do enveloped viruses deliver their genome into the cytoplasm? (3) What are the evolutionary origins of the genes that drive virus entry? (4) How are innate immune responses to microbial nucleic acids generated, amplified and regulated? To answer these questions, we are employing a diverse set of complementary biophysical, biochemical and cell biological approaches.
By integrating approaches across scales (in space and time), we envision moving towards a structure-based understanding of biological processes at the cellular level. Each of our projects has important potential applications in global health.
Shmuel Willensky, Hagit Bar-Rogovsky, Eduardo A. Bignon, Nicole D. Tischler, Yorgo Modis & Moshe Dessau (2016). Crystal structure of glycoprotein C from a hantavirus in the post-fusion conformation. PLoS Pathog., 12, e1005948.
Danillo L.A. Espósito, Jennifer B. Nguyen, David C. DeWitt, Elizabeth Rhoades & Yorgo Modis (2015). Physico-chemical requirements and kinetics of membrane fusion of flavivirus-like particles. J. Gen. Virol, 96, 1702–1711.
Rigby RE, Webb LM, Mackenzie KJ, Li Y, Leitch A, Reijns MA, Lundie RJ, Revuelta A, Davidson DJ, Diebold S, Modis Y, MacDonald AS, Jackson AP (2014) RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J. 33:542-58.