Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Organelle shape and function in the context of viral infections   (#121)

Ileana M Cristea 1
  1. Princeton University, , United States

Shape and function are tightly linked in biology. At the tissue and cell level, an alteration in shape induces the activation of numerous signaling cascades. This ability to transmit information regarding shape is essential for numerous biological processes, including the sensing of mechanical force during development. At the intracellular level, changes in the shape of cellular organelles are core components of cell cycle, metabolism, apoptosis, and transcriptional regulation. This tight link between organelle shape and function is exploited by viruses during infections as mechanisms acquired to either support virus replication or inhibit host defense responses. Here, we investigate mechanisms underlying alterations in shape and the molecular function of these changes in different biological contexts. For these studies, we integrate microscopy, proteomics, lipidomics, and the development of mathematical modeling and computational platforms for data analysis. We uncover finely-tuned temporal alterations in organelle shape that are used to either activate or inhibit specific organelle functions at different stages of infection. Examples include peroxisome alterations that induce metabolic changes to support virus production, as well as mechanisms controlling lamina integrity at the nuclear periphery to inhibit virus capsid egress. Our studies also point to shape alterations that are connected to protein movements between organelles and changes in protein interactions. We present our efforts to globally characterize the formation and dissociation of protein interactions during the progression of herpesvirus infection. Finally, we report the development of a computational platform that allows the users to visualize protein interactions that are dynamic in space and time, and to integrate information of subcellular localization, functional annotations, and protein abundances.