MRes in Medical Mycology and Fungal Immunology

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Project 1: The role of novel C-type lectin receptors in adaptive anti-fungal immunityProject summary - Fungal infections pose an enormous burden on human health, particularly in individuals with altered immune systems. Developing a greater understanding of how the immune system actually provides protection against fungal diseases is critical if we are to use this knowledge to develop novel therapies to combat these infections. We previously discovered that a key molecule expressed on the surface of immune cells, called Dectin-1, plays a central role in antifungal immunity. Our subsequent research revealed that Dectin-1 protects the gastrointestinal (GI) tract from infection with Candida albicans, a fungal organism that is commonly associated with humans, but that can cause devastating diseases in individuals whose immune functions are compromised. Notably, we found that absence of Dectin-1 led to aberrant immune responses following infection with C. albicans, which resulted in a loss of important functional cells, called T-cells, in the infected GI tract. We have recently determined that Dectin-1 controls expression of a novel group of molecules that are involved in the development of these critical T-cell responses. In this application, we propose to characterise the expression and function of these exciting new molecules and establish how they contribute to antifungal immunity in the GI tract.Project 2: : Impact of Adaptive prediction in a major fungal pathogen.Adaptive prediction is an evolutionary mechanism where the microbes that encounter sequential environmental conditions have learned the sequence of events. When the microorganism encounters a primary environmental input, it has evolved to pre-activate the adaptive response against the second input, before it is encountered. This mechanism can confer significant selective advantage to pathogenic microbes as they become primed for future nutritional changes and immune attach. The major human fungal pathogen Candida albicans appears to have evolved adaptive prediction to enhance its ability to colonise certain niches in humans. For example, when C. albicans cells contact the bloodsteam they are exposed to glucose which activates an oxidative stress response that prepares them for subsequent phagocytic attack. Also, the induction of yeast-hypha morphologies triggers the activation of zinc and iron scavenging and toxin candidalysin synthesis, thereby preparing the fungus for foraging in host tissues where these essential micronutrients are limiting.