Project No.2226

Primary Supervisor

Dr Rebecca Hall – University of Kent

Co-Supervisor(s)

Dr Anthony Lewis – University of Portsmouth

Summary

Candida albicans is an opportunistic fungal pathogen that forms part of the natural flora of the oral, genital and gastrointestinal tracts of healthy individuals.

However, changes in the host’s environment or immune status, enable the pathogen to outcompete our immune defences resulting in approximately 400,000 systemic infections and 140 million mucosal infections each year. Systemic C. albicans infections are associated with high mortality rates (up to 50%), with limited antifungal treatments available. Therefore, understanding the factors that promote fungal pathogenicity are key to the development of new antifungals.

The major drivers of fungal pathogenicity are changes in environmental pH and accessibility of essential nutrients and ions. Recently, we have shown that adaptation of C. albicans to acidic conditions results in remodelling of the fungal cell surface which consequently impacts the host-pathogen interaction, and that the pH sensitive cation channel Tok1 plays an important role in the adaption of C. albicans to environmental pH. However, how these processes are linked to enable C. albicans to survive within the human host are unknown. Through the use of clinical isolates, reverse genetics, and biochemical characterisation of Tok1, you will elucidate how C. albicans adapts to pH, and the role ion acquisition plays in this adaptation process. Then, armed with this knowledge, you will address how this adaptation influences the host-pathogen interaction. To achieve these aims you will employ skills in molecular microbiology including global transcriptional analysis (RNA Seq), proteomics, fungal genetics, flow cytometry, cell biology, biochemistry, immunology and electrophysiology. You will receive a combination of in-house and external training to equip you with the skills you require for a successful PhD and future scientific career.