Speaker: Keir Balla, Chan Zuckerberg Biohub San Francisco group leader of infectious disease and quantitative cell science

Title: "Discovering viruses and studying immunity in a zebrafish RNAquarium"

Abstract: Virus infections begin within a localized region, often initiated by a single virus particle in a single host cell. The host response to infection is amplified beyond single cells by genetic and cellular networks that orchestrate system-level antiviral immunity. While many of the cells and signaling modules involved in immune responses to viruses have been outlined, we lack a full picture of how antiviral immunity scales from individual cells to animals. We have developed an in vivo system for investigating antiviral immunity using zebrafish, which is unique among genetically tractable vertebrate models in being amenable to both animal-wide imaging and cellular profiling. Our group leverages these strengths along with naturally occurring viruses that we have discovered in laboratory zebrafish, allowing for systematic investigations of the interactions between co-evolving host-virus pairs. The first virus that we discovered is a relative of poliovirus in the Picornaviridae family, which we found to be widespread in zebrafish research facilities. Our discovery of a naturally occurring virus in typical laboratory settings motivated us to extend our searches for additional viruses. One approach that we are taking is to leverage the popularity of RNA-sequencing in research with zebrafish by systematically re-analyzing all of the >50K publicly available datasets in NCBI's sequence read archive to discover viruses and detect host responses to infections. Our searches have yielded many additional viruses and a comprehensive overview of gene expression patterns across a panoply of zebrafish datasets. We plan to deploy the diverse suite of naturally occurring viruses we are discovering in system-wide investigations of infection biology, and to generate a resource around the genetic compendium of host and microbe transcript data we are generating for the community of researchers that use zebrafish and beyond.

Hosts: Raquel Espin Palazon, GDCB assistant professor, and Clyde Campbell, GDCB adjunct assistant professor