EASTBIO Melanin – the struggle between light and darkness

Melanins are black-brown pigments synthesized in living organisms across all kingdoms for purposes including anti-oxidation protection, sclerotization (or seed hardening in plants) and colour patterning (or absorption of light for plant seeds), clot formation, organogenesis, and innate immunity. They are also produced in opportunistic human pathogenic yeasts such as Histoplasma capsulatum, Paracoccidioides brasiliensis, Cryptococcus neoformans and Candida albicans. In C. neoformans, melanin is a major virulence factor associated with the fungal cell wall and plays a role in protection against environmental stressors, host immunity and antifungal therapies. Another equally important pathogenic yeast, Candida albicans, also produces melanin, though its role in virulence is largely underexplored.

Previously, we found that inhibiting the uptake of nonopsonized C. neoformans and C. gattii in waxmoth (Galleria mellonella) larvae partially protects the larvae from infection by both fungi. The low levels of internalised nonopsonised Cryptococci is accompanied by the low levels of proinflammatory cytokine production. This potentially facilitates fungal pathogenesis through a (fungal) melanin-dependent route. More recently, we found that when the human pathogenic bacteria, Yersinia pseudotuberculosis, was unable to adhere to phagocytes from the waxmoth larvae due to the loss of an adhesin, (insect) melanin is produced. Surprisingly, while the melanin produced clears the pathogen, it also increased phagocyte death and host mortality. This suggests a fascinating interplay between host response in insects and microbial pathogenesis with melanin as key player. Therefore, the AIM for this studentship is to determine the contribution of melanin from yeast and insect on pathogenesis and to identify the mechanisms by which this process occurs. The specific OBJECTIVES are to 1) Investigate the virulence of clinical isolates and mutants of Candida albicans and Cryptococcus neoformans in Galleria mellonella; 2) Determine the different genetic, chemical and biological cell wall composition from yeasts which contribute towards virulence; 3) Dissect the role of insect and fungal melanin in fungal pathogenesis.

Candidates should have (or expect to achieve) Molecular/Cell Biology/Biochemistry or other related disciplines and/or an M.Sc. (or appropriate lab experience) is recommended for this very highly competitive programme. A minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

This is a full-time opportunity.