Synthesis and exploration of new antibiotics using an integrated synthetic biology and organic chemistry approach

Applications are invited for a PhD studentship in the study of the structure and dynamics of DNA-DNA and small molecule-DNA interactions with a view to designing new antibiotics.

Background – There is an urgent need to design and develop new antibiotics to cope with the global spread of antimicrobial resistance. Finding new antibiotics is difficult and the majority of antibiotics used in the clinic are from natural sources, particularly from Streptomyces bacteria. Streptomyces are harmless soil bacteria that have a huge capacity to make useful bioactive molecules. Our approach to addressing this critical problem of antibiotic resistance is to integrate synthetic biology with synthetic organic chemistry by engineering Streptomyces bacteria to prepare new antibiotics by the addition of new small molecule feedstocks.

The challenge - It remains a significant societal challenge to develop new antibiotic scaffolds which thwart bacterial resistance. This studentship will explore an innovative approach to address these significant challenges using the DNA-binding natural product netropsin as the starting scaffold.

The project – You will synthesise novel heterocyclic building blocks that recognise unique DNA sequences. The heterocycles will also favourable drug-like properties. In collaboration with the Hoskisson group in the Strathclyde Institute for Pharmacy and Biological Sciences (http://spider.science.strath.ac.uk/sipbs/staff/Paul_Hoskisson.htm) you will develop methodology that incorporate these building blocks into netropsin scaffolds. Finally, in collaboration with Neil Hunt (http://phys.strath.ac.uk/information/acadstaff/neil.hunt.php), you will develop an understanding of how these compounds bind to their target sequence using our state of the art femtosecond laser 2D-IR spectrometer.

Techniques gained from this project - You will be exposed to both solid and solution phase synthetic techniques for the preparation of small and medium sized molecules, develop new synthetic biological techniques in collaboration with a second PhD student (based in the Hoskisson group) and explore IR spectroscopy as a new tool for the characterisation of molecular interactions with DNA (Hunt group).

Multi-disciplinary collaboration – This is a joint project between the Departments of Pure and Applied Chemistry (Dr Glenn A. Burley), SIPBS (Dr Paul Hoskisson) and Physics (Dr Neil Hunt). You will also interact with synthetic chemists, chemical biologists and biochemists as part of WestChem's graduate school.