Synthesis and evaluation of new antimicrobials

With the prevalence of drug-resistant infection on the rise there is a real and urgent need to develop new antimicrobial agents active against a range of microbial pathogens (bacteria, fungi, protozoa). One disease which we are particularly interested in developing a licensed treatment for is Acanthmoeba Keratitis (AK). AK is a blinding infection in the eye caused by the organism Acanthmoeba. The current (unlicensed) gold standard treatment of this condition is use of the poly(hexamethylene biguanide) (PHMB), a commercial broad spectrum polymeric antimicrobial often used as a pool disinfectant. In many cases however the patients do not respond well to this therapy, the eventual result being surgical removal of the eye following irreversible destruction of corneal tissue. Clearly there is a need for the development of improved therapies for the treatment of AK.

In this project the candidate will firstly undertake the synthesis of a family of compounds bearing a range of cationic functionalities known to possess antimicrobial activity (e.g. guanidines, biguanides) and subsequently screen their antimicrobial activity against Acanthamoeba. Subsequently, precision polymer synthesis techniques will be used to elaborate these small molecule antimicrobials to prepare polymers with a range of macromolecular architectures with a view to understanding the relationship between structure and activity. Importantly, elaboration of these antimicrobials into polymers is expected to further limit any development of resistance, due to the anticipated mode of action (physical rupture of cell membranes).

Applicants should have a recognized Honours or Masters degree with a 2.1 or equivalent in Chemistry (or a related field). The successful candidate will be trained in a range of advanced synthetic techniques used in the preparation of functional small molecules and precision polymers and develop skills in microbiology. Laboratory work and characterization will be undertaken within the University of Wolverhampton’s Science Centre, the Rosalind Franklin building, which houses a broad range of state-of-the-art research facilities suitable for undertaking this multidisciplinary project. 

Further details can be obtained via direct email to Dr Daniel Keddie ([Email Address Removed]) or Dr Wayne Heaselgrave ([Email Address Removed]).