Sense and respond: Investigating molecular mechanisms regulating Cryptococcus neoformans Titan cell formation in response to bacterial triggers (360G-Wellcome-211241_Z_18_Z)

£923,828

This fellowship investigates fungal-bacterial interaction in a major human fungal pathogen to test the hypothesis that conserved mechanisms of non-self surveillance trigger morphogenesis driving pathogenesis. During lung infection with the fungus Cryptococcus neoformans, small haploid yeast switch to large, highly polyploid Titan cells, markers of pathogenicity. I recently demonstrated that Titanisation is a regulated transition triggered by bacterial peptidoglycan. Peptidoglycan sensing by mammals and plants is well described, however mechanisms of peptidoglycan sensing in fungi remain unknown. My data contribute to growing evidence that peptidoglycan, a ubiquitous bacterial ligand, influences morphogenic transitions in fungi. In the environment, C. neoformans associates with bacteria that modulate fungal virulence. In patients, Titanisation occurs in the lung. Contrary to dogma that the lung is sterile, healthy lungs are colonized by gram-negative and gram-positive bacteria. My preliminary data suggest peptidoglycan subunits regulate two aspects of Titanisation: cell cycle (endo-reduplication leading to polyploidy) and cell size (switch from budding to isotropic growth). Here, I will dissect mechanisms underlying peptidoglycan-induced Titanisation, and suggest peptidoglycan acts via dual signaling pathways. This work will improve our understanding of cross-kingdom signaling modulating pathogenesis in a major human fungal pathogen.

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Grant Details

Amount Awarded 923828
Applicant Surname Ballou
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2018-06-06T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Sir Henry Dale Fellowship
Internal ID 211241/Z/18/Z
Lead Applicant Dr Elizabeth Ballou
Partnership Name Royal Society/Wellcome Trust Sir Henry Dale Fellowship
Partnership Value 923828
Planned Dates: End Date 2021-05-20T00:00:00+00:00
Planned Dates: Start Date 2018-09-30T00:00:00+00:00
Recipient Org: Country United Kingdom
Region West Midlands
Sponsor(s) Prof Chris Bunce