Research in the Sherlock lab
Research in the Sherlock lab
We are interested in unique strategies used by viruses to translate viral mRNAs into proteins during infection. We want to understand the structure, function, mechanism, and conservation of RNA motifs within viral mRNAs that cause non-canonical translation events. These RNA structures can help evade host cell defense systems, enable translation of open reading frames that are otherwise inaccessible to the ribosome, and regulate viral protein expression levels.
One area of focus in the lab is translation termination-reinitiation, in which a ribosome fails to recycle and dissociate from an mRNA after one round of translation, leading to "re-initiation" and translation of a second, downstream open reading frame in a manner independent of the 5′ and 3′ ends.
The Sherlock lab uses molecular biology, biochemistry, and structural biology approaches such as reporter assays, chemical probing, and cryoEM to investigate these mysterious viral RNA structures.
Different types of non-canonical translation events can express alternative protein products and regulate gene expression. We are particularly interested in reinitiation events, especially those induced by RNA structures.
Read more here about translation reinitiation.
Programmed reinitiation enables expression of downstream open reading frames. Read more here about the identification of new viral reinitiation-stimulating RNA elements and their structures as revealed by cryoEM.