Structure, mechanism and dynamics of recoding in viral infection

Accurate translation of mRNA by the ribosome is essential for all life. It is therefore a high-fidelity process, with spontaneous error rates of only ~ 1 in 100,000 codons. When RNA viruses infect cells they frequently make proteins that differ from the genetically encoded sequences. These highly-regulated 'recoding' events are vitally important to viral gene expression, and if disrupted many viruses (e.g. SARS-CoV-2, HIV-1) fail to complete their replication cycles. I aim to use a multidisciplinary approach to better understand recoding, initially focussing on -1 programmed ribosomal frameshifting (PRF) in SARS-CoV-2, HIV-1 and EMCV. Using single-molecule fluorescence microscopy, I will observe PRF in real-time both in vitro and in live cells. I will also reveal mechanistic details by time-resolved cryo-EM, crystallographic and biophysical studies. Together, this work will reveal universal structural and mechanistic principles that govern mammalian recoding, laying the foundations for developing a new class of antiviral drugs.