Research Associate in Biological Chemistry (Manchester Institute of Biotech

at  The University of Manchester

‘A VERSATILE BIOCATALYTIC PLATFORM FOR PRODUCTION OF THERAPEUTIC SGRNAS’

A position is available for a Postdoctoral Research Associate with experience in directed evolution, biocatalysis, biochemistry or a related discipline. The aim of the research is to develop and optimize biocatalytic approaches to single guide RNAs (sgRNAs) that have applications in CRISPR based gene therapy.
CRISPR-based therapeutics are emerging as a promising new drug modality for the treatment of a range of disease areas including cancers, genetic disorders and viral infections. Here a single guide RNA (sgRNA) directs the CRISPR/Cas9 complex to the target gene which is subsequently edited. sgRNAs are currently produced using solid phase phosphoramidite chemistry involving iterative cycles of coupling, capping, oxidation and deprotection to achieve stepwise extension of RNA sequences immobilized on solid supports. Given that sgRNAs are typically 100-150 nucleotides long and impurities are introduced during each nucleotide extension, target sequences are produced in very low yields and require complex HPLC purifications. To synthesize sgRNAs in the high volumes and high purities needed for therapeutic applications, more efficient synthetic methods are required. The Lovelock group are interested in the development of biocatalytic strategies to produce long oligonucleotide sequences. This research involves process optimization, scale up and optimization of biocatalyst properties using directed evolution to make them suitable for pharmaceutical manufacturing processes.
This is a highly interdisciplinary project at the cutting edge of enzyme engineering and nucleic acid therapeutics research and the successful applicants will have full access to state-of-the-art facilities for reaction scale-up and high-throughput automated enzyme engineering, including liquid handling robots, colony pickers and a suite of high throughput analytical facilities. The successful candidates will have the opportunity to apply and further develop their expertise in both fundamental and translational science, which are highly relevant to a future career in the pharmaceutical and wider chemical industry.
Applicants should have, or are expect to attain a PhD or equivalent, in Biological Chemistry, Biochemistry or Biocatalysis, and have a thesis submitted prior to taking up the position. You should be capable of working under your own initiative but also collaborating with industrial and academic research partners, so excellent communication and organisational skills are required.

Please refer the Job description for details