Description of Research Expertise

Research Interests:
The Price Lab studies how DNA viruses take over and subvert host cell biology, with a particular focus on how viruses steal cellular RNA processing machinery to make viral RNA. While viruses have evolved to be masters of molecular mimicry, viruses are constrained by a hard limit on maximum genome size. Any viral process that deviates from standard cell biology allows a host cell to sense infection, and transcription of these small genomes can lead to aberrant nucleic acids that can be sensed by the innate immune system. Beyond virology, our research reveals how transcriptional processes affect innate immunity and inflammation, with broad implications for the progression of autoimmune diseases and cancers where RNA biogenesis has become dysregulated.

Rotation Projects:

1. How is nuclear dsRNA sensed and responded to during viral infection? Immunostimulatory dsRNA produced during viral infection is thought to be sensed in the cytoplasm, however DNA viruses or endogenous sources produce dsRNA in the nucleus. Potential projects will involve using mass spectrometry to identify novel interactors of dsRNA within the nucleus and tracing the substrates of existing, but relocalized, antiviral sensors.

2. How do DNA viruses spatially regulate RNA transcription and processing? Viruses must balance replication of their genomes with production of RNA messages. Furthermore, clashes between replication and transcription machinery can indirectly damage viral DNA. High resolution microscopy will be performed to assess how the sites of synthesis of both viral RNA and DNA change over the course of infection. How this process is regulated will be interrogated with mass spectrometry for cellular factors that regulate this switch.

3. How does RNA processing occur in genomes 100 times as dense as the human genome? Viral genomes are incredibly gene rich, yet they obligately use cellular machinery that is evolved to produce cellular RNA. Novel approaches such as Oxford Nanopore long-read sequencing and nascent RNA capture and sequencing will be performed to discover how viruses maintain the fidelity of their transcriptomes.