Fuelling pathogenicity: nutrient adaptation of human fungal pathogens (360G-Wellcome-214317_Z_18_Z)

£1,712,381

During infection, mammalian hosts restrict the availability of key micronutrients in a process called "nutritional immunity". To cause disease, pathogens have evolved ways to circumvent this restriction. Building on discoveries made in my Sir Henry Dale Fellowship, this proposal addresses three key aspects of Candida albicans nutrient adaptation during colonisation and infection. I will define the signalling pathways orchestrating intracellular nutrient trafficking. Eukaryotic pathogens have the unique capacity to store high levels of micronutrients. I have shown that this fuels virulence and will now dissect the molecular mechanisms and regulatory pathways governing this important process. I will determine the mechanistic basis of competition for zinc at the host-pathogen interface. Having discovered the first zincophore zinc scavenging system of any pathogen, I will now structurally resolve this crucial micronutrient assimilation protein and show how it allows fungi to secure this essential micronutrient during infection. I will show how C. albicans Goliath cells, a novel morphotype I recently discovered, pioneer the colonisation of the mammalian gut. Here I will take advantage of this seminal discovery to understand how C. albicans establishes it commensal niche.

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Grant Details

Amount Awarded 1712381
Applicant Surname Wilson
Approval Committee Science Interview Panel
Award Date 2018-11-27T00:00:00+00:00
Financial Year 2018/19
Grant Programme: Title Senior Research Fellowship
Internal ID 214317/Z/18/Z
Lead Applicant Dr Duncan Wilson
Partnership Value 1712381
Planned Dates: End Date 2019-08-31T00:00:00+00:00
Planned Dates: Start Date 2019-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland