| Title | DNA-Binding Antibiotics - Targeting multidrug resistant bacteria. |
|---|---|
| Supervisor | Nicholas Tucker |
| Research Area | Molecular Biology Microbiology Genomics Antibiotic Resistance Gene Regulation Transcription Chemical Biology Medicinal Chemistry |
| Description | Transcription is an essential process in biology making it an attractive target for drug discovery. However, rising levels of antibiotic resistance dictate that novel modes of action must be found. DNA-binding drugs have shown promise in a wide variety of clinical applications, yet few definitive examples of their modes of action exist. We have recently investigated the mode of action of a novel antibiotic that is a member of a family of synthetic DNA minor groove binding (MGB) molecules. MGB-BP3 has successfully completed a Phase 1 clinical trial in humans as an orally administered drug for the treatment of chronic Clostridium difficile infections. MGB-BP3 is active against a variety of Gram-positive pathogens including Staphylococcus aureus, against which it has better activity than vancomycin. The aim of this project is to expand the repertoire of activity of MGB antibiotics so that individual regulons in Gram-negative bacteria can be targeted. Novel methods will be developed that use our illumina genome sequencer to report the binding profile and transcriptional effects of new MGB drugs. |
| Techniques Used | This project will provide direct access to our illumina genomics instrumentation so this project would suit a student who is keen to develop their skills in molecular biology and bioinformatics. |
| References | Barrett, M. P., Gemmell, C. G., & Suckling, C. J. (2013). Minor groove binders as anti-infective agents. Pharmacology & Therapeutics, 139(1), 12–23. http://doi.org/10.1016/j.pharmthera.2013.03.002 Suckling, C. J. (2015). The antibacterial drug MGB-BP3 : from discovery to clinical trial. Strathprints.Strath.Ac.Uk ¬ Lemonidis, K., Salih, T. S., Dancer, S. J., Hunter, I. S., & Tucker, N. P. (2019). Emergence of an Australian-like pstS-null vancomycin resistant Enterococcus faecium clone in Scotland. PloS One, 14(6), e0218185. http://doi.org/10.1371/journal.pone.0218185 Freschi, L., Bertelli, C., Jeukens, J., Moore, M. P., Kukavica-Ibrulj, I., Emond-Rheault, J.-G., et al. (2018). Genomic characterisation of an international Pseudomonas aeruginosa reference panel indicates that the two major groups draw upon distinct mobile gene pools. FEMS Microbiology Letters, 365(14), W16. http://doi.org/10.1093/femsle/fny120 |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. Experience in molecular biology is advantageous. |
| Bench Fee | Running costs of £10000 p.a. will be associated with this project in addition to University tuition fees. |
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