Research Associate- Welch Group: Global reprogramming of virulence and AMR in Pseudomonas aeruginosa bymutations in FusA1 (Fixed Term)

Applications are invited for a Research Associate position in the laboratory of Professor Martin Welch in the Department of Biochemistry, University of Cambridge.

Mutations in fusA1 are now recognized as being responsible for high level resistance to aminoglycoside antibiotics. These mutations are particularly prevalent in the critical priority pathogen, Pseudomonas aeruginosa, which is ubiquitous in the built environment and is a major cause of potentially life threatening infections in immune-impaired individuals and among people who are genetically pre-disposed towards infection (eg, people with CF). However, we currently have little idea about why mutations in fusA1 lead to AMR. FusA1 encodes a probable ribosome recycling factor helping ribosomes to "drop off" the mRNA message when they encounter a "stall signal". Ribosomal pausing at most stall sites is usually easily overcome if the FusA1 is functioning normally. However, based on our preliminary experiments, we suspect that the ability of mutant forms of FusA1 to facilitate ribosome recycling may be altered, thereby changing the dynamics of translation. For example, if dissociation of
ribosomes from key "stall sites" or stop signals becomes even slightly impaired, ribosomes will start to queue-up at such sites, affecting the translation of the protein encoded on the mRNA. If that protein was itself associated (either directly or indirectly) with aminoglycoside resistance, this would provide a tangible link between the mutation in fusA1 and the AMR phenotype.

This problem will be investigated using RNA-seq, Ribo-seq and ChIP-seq, and structural analyses, as well as the specialized proteomic approaches of TurboID and "OOPS" and biochemical assays. The project will also involve short-term travel to other laboratories and close collaboration with a network of researchers across Cambridge and beyond.

Research Associate- Welch Group: Global reprogramming of virulence and AMR in Pseudomonas aeruginosa bymutations in FusA1 (Fixed Term)