Topic: ribosome stalling

A four-year Cambridge–AstraZeneca PhD beginning 1 October 2027 investigates 2A peptide sequences that separate proteins during translation. The project aims to reduce ribosome stalling, drop-off and separation failure and optimise new sequences for biotechnology and cell-therapy applications. Work spans the Department of Pathology and AstraZeneca Discovery Centre, combining molecular biology with opportunities in bioinformatics and structural biology. Supervisors are Andrew Firth and Giovanni Ciotta. Funding covers the University Composition Fee and maintenance expected to begin at approximat

Silencing of FMR1 and loss of its gene product, FMRP, results in fragile X syndrome (FXS). FMRP binds brain mRNAs and inhibits polypeptide elongation. Using ribosome profiling of the hippocampus, we find that ribosome footprint levels in Fmr1-deficient tissue mostly reflect changes in RNA abundance. Profiling over a time course of ribosome runoff in wild-type tissue reveals a wide range of ribosome translocation rates; on many mRNAs, the ribosomes are stalled. Sucrose gradient ultracentrifugation of hippocampal slices after ribosome runoff reveals that FMRP co-sediments with stalled ribosomes,