A chemistry-first approach to uncovering novel natural products from a proprietary species collection of rare and unexplored bacteria

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 A chemistry-first approach to uncovering novel natural products from a proprietary species collection of rare and unexplored bacteria

Supervisors: Ellis O’Neill (University of Nottingham) and Mark Wilkinson and Sibyl Batey (Bactobio)

An exciting opportunity with an industrial collaborator to gain in depth training in natural product discovery, chemical analysis and bioassay development.

Natural products are incredibly diverse and complex. These small molecules are produced by microbes as secondary metabolites to facilitate their interaction with other organisms. One third of new small molecule drugs since 1981 are derived from natural products and some 80% of all existing antibiotics derive from soil bacteria including our most critical antibiotics, such as vancomycin and erythromycin. This project will combine expertise of the O’Neill lab in high throughput molecular networking and genome mining alongside Bactobio’s unique species library and industrial experience to take a chemistry-first approach in discovering novel natural products for application in pharmaceutical or agritech industries.

In this project the student will grow the unique bacterial collection and analyse the natural products made under different growth conditions. The key enabling technology for this research is mass-spectrometry based molecular networking, enhanced with machine learning algorithms, to analyse complex cell extracts and identify which compounds to focus research efforts on. These natural products will then be purified, and their structures characterised using analytical chemistry techniques, including NMR and mass spectrometry. Additionally, the genomes of the producing strains will be investigated to uncover the biosynthetic pathways responsible for the biosynthesis of the compounds using genome mining and gene editing. All molecules discovered in this project will undergo extensive bioactivity testing against medical and agricultural challenges.

Ellis O’Neill is an Assistant Professor in the School of Chemistry at the University of Nottingham. His research focuses on natural product discovery and microbial metabolism. Mark Wilkinson is Chief Scientific Officer at Bactobio, where he oversees scientific projects and has expertise in high-throughput screening and genome mining. Sibyl Batey is a Senior Scientist at Bactobio, within the Compound Discovery Team, purifying and characterising novel bioactive metabolites.

The Offer

This is a fully funded studentship for 48 months to commence October 2023, with tuition fees paid, and full tax-free stipend matching the RCUK rate (currently £17,668 per annum). This project will give the student a unique opportunity to gain experience of bacterial culturing, chemical analysis, genome mining and bioactivity assays in both academic and industrial settings. The majority of research time will be based at the University of Nottingham, but the student will also spend substantial time at the London base of Bactobio throughout the project.

Candidate Requirements

Applicants should have, or expect to achieve, at least a 2:1 Honours degree (or equivalent) in Chemistry, Biochemistry or a related subject with substantial analytical chemistry or biological chemistry content and a strong interest in biochemistry/microbiology. A relevant Master's degree and/or research experience will be an advantage.

 Apply online here by noon on Tuesday 17^th January 2023.