Single-Cell Analysis of Virus-Host Interactions

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DESCRIPTION (provided by applicant): Animals are home to cells of hundreds of microbial species, far outnumbering the cells comprising the organism itself. However, we still remain largely ignorant of the diversity of the viruses that inhabit such environments and the identity of their hosts. Further, the ecological role of these viruses is even more unclear. As such, viruses in many ways are the dark matter of the microbial universe. We argue that one of the central challenges in environmental microbiology is to map out which viruses are associated with which hosts and understand the flow of genetic information in this complex web of interactions. In the work proposed here, we build on our earlier efforts using digital PCR on termite hindgut samples to colocalize viruses with their hosts. In particular, we will use digital PCR to explore virus-host interactions in other environments such as mammalian guts. In addition, our plan is to build upon these earlier efforts by performing single-cell sequencing on termite and mammalian gut samples thus providing access to tens of full genomes of the viruses (prophages) as well as the genomes of the bacteria they infect. With such unprecedented genetic resolution we hope to redefine the current understanding of how viruses interact with their hosts in the wild, potentially uncovering new fundamental mechanisms of interaction. PUBLIC HEALTH RELEVANCE: In recent years it has become increasingly clear that human health is directly tied to the microbial communities we harbor within us. The work proposed here begins to explore the way in which viruses can impact these microbial communities. We expect that just as different humans have different microbial community structures with corresponding implications for their health, the structure of the viral communities will add another dimension to our growing understanding of the health consequences of our partnerships with the microbes that populate us.