EAGER: Toward a tractable genetic model of DNA virus - Drosophila interaction

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DNA viruses are a difficult problem in health care and a widely-used tool for managing pest populations, particularly in agriculture. However, researchers lack good models to study the interactions between DNA viruses and their hosts. This project aims to create a tractable genetic model for studying host/DNA virus interaction using fruit flies (Drosophila), one of the most widely used model organisms. This advance would allow for genetic manipulation of the virus through standard laboratory techniques to better understand the molecular genetic basis of virulence, host manipulation, and the emergence and evolution of infectious disease. Researchers will also optimize the growth of the nudivirus in cell lines, making possible a drove of experiments in the future. In addition, the project would train undergraduate researchers from a transfer student program to provide them with hands-on scientific training and contribute to broadening participation in science. The first objective is to create new cell lines and optimize conditions for viral replication. To date available cell lines have been used to grow the virus with limited success. Utilizing new cell lines based on natural host tissues and optimized conditions promises to improve viral replication in cell lines. The second objective is to clone the large, double stranded DNA genome into a bacterial artificial chromosome for ease of production, then show that genetic manipulation of the virus is straightforward using standard site-directed mutagenesis and PCR-based recombinant techniques. Upon project completion, researchers will have developed a versatile, tractable system for studying host/DNA virus coevolution that can be used to inform treatment of DNA virus diseases and biocontrol strategies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.