Research in the Cherry lab is aimed at identifying cellular factors that regulate viral pathogenesis, including both those factors hijacked by viruses for replication and those innate anti-viral mechanisms used by the host to combat the invader. To identify these factors we are taking a genetic approach by screening for factors that impact viral replication. To this end, we are using the model genetic organism Drosophila. This allows us to use a wide-variety of techniques to identify these genes including both high-throughput RNA interference screens in cell culture, and forward genetic screens in animals. Moreover, we are also screening for host factors in human cells using high-throughput RNA interference screening technologies. We are using these approaches to study a number of arthropod-borne RNA viruses, including the flavivirus West Nile virus, the alphavirus Sindbis and the bunyavirus Rift Valley Fever virus. These are the three major families of viruses that are important human pathogens transmitted by mosquitoes to humans. By screening in both hosts- insect and human- we hope to gain a more comprehensive understanding of the host factor requirements of these pathogens. We are currently characterizing the roles of candidate genes already uncovered by using molecular biological and cell biological techniques and have discovered factors involved in viral replication and innate immunity. By combining these methodologies, and using a variety of viruses, we hope to gain a comprehensive understanding of the interplay between the host and pathogen in a complex and dynamic setting. Taking advantage of forward genetics and functional genomics in will allow us to use these unbiased and global methodologies to identify many important and novel host factors that modulate virus-host interactions. Moreover, the more viral-host pairs that we study, the better our understanding of pathways and processes essential to pathogens, and the more equipped we will be to develop anti-viral treatments.
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