A chemical biology investigation of hydrogen peroxide signalling in Toxoplasma
Dr Matthew Child
Imperial College London, United Kingdom
When viruses infect a cell they often display structures that are sensed as foreign. After detection, signalling pathways result in the production of proteins called interferons. These proteins induce the production of hundreds of other proteins called interferon-stimulated genes in the infected and neighbouring cells to fend off the viral infection.
I have shown that the interferon-induced protein with tetratricopeptide repeats-1 (IFIT1) preferentially binds RNA with improperly processed ends and blocks the production of protein from this RNA. However, the role of IFIT1 in the antiviral response is still not clear since the only viruses affected by this RNA binding activity are those genetically engineered to be susceptible. There is also evidence to suggest that IFIT1 can bind fully processed RNAs. My hypothesis is that IFIT1 can interact with cellular RNA and that this interaction is important for the antiviral response. I will use multiple cutting-edge RNA/protein analysis approaches to determine what RNAs IFIT1 binds and their fate, how RNA binding regulates IFIT1 protein-protein interactions and what affect IFIT1 has on translation in the whole cell.
By understanding the impact of IFIT1 on the cell we will gain an insight into its role in the host antiviral response.