Research Interests

Viruses that infect Caenorhabditis nematodes

Model organisms have proven invaluable in defining processes central to human biology. For example, the caspase cell death pathways were initially described in C. elegans, and seminal studies of RNAi were also performed in C. elegans. However, C. elegans has been largely ignored as a model to study host-virus interactions due to the absence of known viruses capable of naturally infecting C. elegans. In collaboration with the laboratories of Marie-Anne Felix (Institut Monod) and Eric Miska (Cambridge), we discovered the first two viruses, Orsay virus and Santeuil virus, that naturally infect wild isolates of C. elegans and C. briggsae, respectively. These two viruses are most closely related to known viruses in the family Nodaviridae, but have only low levels of sequence identity to previously described nodaviruses. Orsay virus is also capable of infecting the N2 laboratory C. elegans strain as well as mutants in this background. We recently identified a 3rd virus, Le Blanc virus, that can infect C. briggsae.

All three viruses appear to share similar tropism and infect a limited number of intestinal cells.

We are currently using this experimental system to identify host proteins that modulate viral infection in Caenorhabditis nematodes. We are employing forward and reverse genetic screens in C. elegans to identify host factors that are either pro-viral or antiviral; subsequent studies aim to determine whether the human orthologs of such genes maintain evolutionarily conserved functions.