Antimicrobial resistance represents a global challenge to our health and there is an urgent need to develop new antibiotics to keep one step ahead of the pathogens. Streptomyces bacteria are the source of most antibiotics in clinical use today. They produce a considerable and diverse range of bioactive molecules that are unique to this bacterial group – including calcium-dependent lipopeptide antibiotics (CDAs) that kill antibiotic resistant superbugs such as vancomycin resistant Staphylococcus aureus (VRSA). The CDA antibiotics are synthesised by giant modular enzymes that programme the synthesis of the peptide core.
We have discovered a way of stimulating genetic recombination in Streptomyces bacteria and have discovered that such stimulation favours genetic recombination across different modules of the genes which encode these giant enzymes. This in turn can lead to the programming of different antibiotic structures and provides a novel route to developing new antibiotics.
Nanopore sequencing, pioneered by Oxford Nanopore Technologies, enables the direct electronic analysis of the sequence of single DNA and RNA molecules. This remarkable new technology enables one to determine the sequence of long DNA molecules of the order of thousands, or even tens of thousands of base pairs, and therefore is potentially ideal for characterising the structures of large scale chromosomal DNA rearrangements.
The objectives of this exciting PhD project are to analyse the chromosomal structures in strains that produce different antibiotic structures following hyper-stimulation of recombination. The second key objective is to use cutting edge genomic analysis methods such transcriptomics and translatomics to identify the molecular pathways that are responsible for stimulating genetic recombination in Streptomyces. This research is likely to identify novel insights into genetic recombination pathways in this industrially important and complex group of bacteria.
The student will work within the new Brighton Genomics facility of the School of Pharmacy and Biomolecular Sciences alongside two highly skilled Experimental Officers. The student will receive advanced training in Streptomyces molecular genetics, genomics technologies and associated bioinformatics techniques, providing a solid foundation for a research career in the field of genomics.
The start date for this PhD studentship will be 3 September 2018.
Given the short time timescale for recruitment, interested candidates are urged to contact Professor Smith directly to discuss the details of the studentship and eligibility for the post: firstname.lastname@example.org