Chemistry (MSc by Research)

There are several research topics available for this degree. See below examples of research areas including an outline of the topics, the supervisor, funding information and eligibility criteria:

Antimicrobial resistance (AMR) increasingly threatens our health and well-being, as infectious microbes evolve to become resistant to existing antibiotics. There is an ongoing need to discover new antibiotic classes and bring them to the clinic. The Minor Groove Binder (MGB) drug discovery platform of the Universities of Strathclyde and Huddersfield contains a family of novel compounds one of which, MGB-BP-3, is ready to enter Phase II Clinical Trial for the treatment of Clostridium difficile, in partnership with our developers MGB Biopharma.1 MGBs kill bacteria through binding to their DNA and interrupting essential bacterial metabolism, but importantly, they act at a number of targets within each cell, which means that variants that are resistant to MGBs have not been seen.2,3 We wish to investigate a range of new compounds from the MGB portfolio as potential agents for clinically challenging infections, principally those of the ESKAPE pathogen set, in addition to exploring their capacity to synergise with existing antibiotics.4,5 Beyond this, we are also interest in performing hit to lead optimisation in the antifungal, antimycobacterial and antiparasitic fields.

In a pilot study, we have already shown that in situations where a clinical pathogen has developed resistance to an existing antibiotic, dual therapy with an MGB may extend the effective lifetime of that antibiotic. This would ‘repurpose’ that ailing clinical antibiotic and extend its useful lifetime.

At present, there are a number of interesting avenues of both Chemistry and Biology research, which we wish to evaluate:

Chemistry 1. Design of novel antifungal MGBs 2. Design of novel antimycobacterial MGBs, particularly for TB. 3. Design of novel antiparasitic MGBs. 4. Design of novel antibacterial MGBs effective against Gram-negative pathogens. 5. Investigation of MGB physicochemical property modulation on activity profile against various pathogenic organisms.

Biology 1. Investigation of MGB synergy with a range of clinically relevant antibiotics. 2. Investigation of MGB synergy with a range of efflux pump inhibitors. 3. Investigation of MGB synergy with other MGBs. 4. Investigation of mechanism of action of novel MGBs that are exiting our current synthetic medicinal chemistry pipeline.

This project provides students with the opportunity to contribute to our Global MGB Drug Development efforts, and assist with developing a better understanding of our emerging new class of antibiotic.

Blood flow is severely restricted in the periphery compartments of a tumour biomass, cells in these regions live under hypoxic conditions with limited availability of glucose sugars. What is not clear is if these cells are able to recycle sugars from the surface of dead and lysing cells and, if so, if mannose can be recycled from surface glycans for use as a carbon feed. In this research project, we are proposing to investigate the role of mannose metabolism within hypoxic cancer cells. A number of enzymes are involved in the uptake and transformation of mannose including MPI (phosphomannose isomerase) which controls the flux between catabolism and glycan formation.

In this project we will follow kinetic features of mannose metabolism within a variety of cancer cell lines, under both aerobic and hypoxic conditions. We will investigate the levels of production of MPI using classical activity measurements where the rate of transformation of mannose-6-phosphate to fructose 6-phosphate will be studied. We will use a range of analytical procedures, including both HPAEC-PAD and NMR, to monitor the change in concentration of Mannose, Man-6-P and Fru-6-P as a function of time. In the latter stages of the programme we will study the effect of a range of simple sugar analogues as inhibitors of the catabolic pathway in an attempt to block the triple negative cancer cells from utilising mannose as a carbon feed.

All major areas of chemistry are covered with areas of strength including:

• synthetic organic chemistry
• physical organic chemistry
• carbohydrates, proteins and enzyme chemistry
• organometallic and supramolecular chemistry
• heterogeneous catalysis and adsorption
• thermal methods of analysis and synthesis
• materials chemistry