Next generation mitochondrial inhibitors - a new approach to prevent fungal biofilm formation on med

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Background Human fungal pathogens represent a current global threat to human health. Candida are yeasts that represent the most common human fungal pathogens and several species readily form biofilms on medical implant devices that promote infection in vulnerable patients. Two examples of biofilm forming Candida species are C. albicans, the fourth most commoncause of hospital acquired blood infections, and C. auris, which represents a highly drug resistant species that is rapidly spreading across the clinical landscape. An increase in resistance to available antifungal treatments means that there is an urgent need for new approaches to tackle fungal biofilm growth. Research from the Gourlay lab suggests that the mitochondrial respiratory chain is a point of weakness that can be exploited as a new anti-fungal target. The Moore lab has developed a library of novel small molecules that specifically target components of the Candida respiratory system. The studentship will evaluate these next generation inhibitors within a collaboration between leading experts in drug design (Moore, Sussex), fungal cell biology (Gourlay, Kent) and a global manufacturer of medical implant devices (Smith Medical Inc). The project is highly multi-disciplinary and likely to result in significant results of industrial relevance. Aims of project The focus of the studentship will be to fully characterise the effectiveness of a range of novel fungal specific respiratory inhibitors in preventing biofilm formation on medical grade materials used to manufacture medical implants. This will be achieved using clinically relevant models and cutting edge experimental techniques within the Gourlay and Moore laboratories. Following in silico and biochemical assessment of a library of inhibitors the most effective will be tested in their ability to prevent Candida species biofilm growth. Further experiments will determine the mode of action and molecular basis using a combination of cell biological, genetic and omic approaches.