| Title | Comparative metabolomics of phylogenetically diverse actinomycetes |
|---|---|
| Supervisor | Katherine Duncan |
| Research Area | Marine microbial chemistry Actinomycetes Marine natural products Specialized metabolism Comparative metabolomics Antibiotic Discovery |
| Description | Over 70% of our antibiotics are produced naturally or derived from natural products, the vast majority of them by bacteria. Some bacteria are better at producing this medically relevant chemistry than others. In particular, the actinomycetes are unsurpassed. In the last 15 years, genome sequencing has uncovered the incredible potential of bacteria to produce medically-relevant chemistry. Surprisingly, it has also revealed that even well-studied bacteria maintain the genetic potential to produce many more metabolites than discovered to date. In this work, we focus the bacterial order, Actinomycetales. Although well-studied, the uncovering of knowledge has been far from systematic and the group is both large and evolutionarily diverse. Strains will be selected based on the presence on biosynthetic genes and compared across taxonomic and phenotypic boundaries, to understand what drives biosynthetic diversity and which strains are likely to have more chemical potential. Each strain will also be cultured under a variety of conditions in triplicate and their chemistry profiled using mass spectrometry. This chemistry (parent ions) will then be linked to the BGCs and again compared across taxonomic and phylogenetic boundaries, to see what drives these specialised metabolites and how good are we at predicting them from genome sequences. |
| Techniques Used | Mass spectrometry Genome mining Bioactivity screening (antibiotic) Natural products chemistry e.g. metabolite extraction Computational – comparative metabolomics and comparative genomics Microbiology |
| References | Berdy, J, J Antibiot (Tokyo), 2005. 58: 1-26 Navarro-Muñoz, J. C. et al, BioRxiv https://doi.org/10.1101/445270 Watve, M. G. Arch Microbiol. 2001. 176: 386-390 Wang, M et al, Nat Biotechnol, 2016. 34: 828-37 Duncan, KR et al, Chem Biol, 2015. 22: 460-71 |
| Conditions | The candidate should have a strong foundation in natural products chemistry Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline such as chemistry, biomedical sciences, microbiology or equivalent. Receipt of satisfactory references. IELTS 6.5 or equivalent |
| Bench Fee | Running costs of £10000 p.a. will be associated with this project in addition to University tuition fees. |
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