Genomic Approaches to Identify Host Factors and Mechanisms that Modulate Pathogen Infections

The balance between pro- and anti-viral forces in influenza influences the outcome of a viral infection, yet we have limited knowledge of how the host factors impact disease severity, a gap in knowledge that extends to most host-pathogen interactions. The overall goal of “Genomic Approaches to Identify Host Factors and Mechanisms that Modulate Pathogen Infections” is to develop a universal experimental platform able to identify host factors that regulate infections by viruses and a diverse range of other pathogens. The route to this goal adapts CRISPR technology to perform genome-wide genetic screens for pro- and anti-pathogen host factors, using a system where the pathogen itself programs CRISPR to modulate host gene expression, thus forcing the pathogen to do the “heavy lifting” that pinpoints cellular regulators of infection.

After identifying new host factors that control influenza replication, experiments will determine the molecular mechanisms of the newly identified regulators. These experiments will establish a mechanistic understanding of viral and host factors regulating infection, yielding detailed knowledge and new targets that can be exploited for the rational development of antiviral therapies. Moreover, this will establish a platform that can be quickly adapted to study host-pathogen interactions in almost any system.