Population structure and pathogenicity of C. neoformans in Vietnam. (360G-Wellcome-097147_Z_11_Z)

£1,443,852

Most cryptococcal meningitis occurs in patients with underlying immune deficit. Occasionally, disease occurs in immunocompetent patients. Using AFLP and MLST, we have made the novel finding of a genotype of C. neoformans var. grubii, VNIgamma, that causes 92% of disease in the immunocompetent but only 35% in HIV patients. Genotypes do not segregate by HIV risk group, gender, or temporally, suggesting the novel type has increased pathogenicity. This hypothesis drives the fellowship. Pathogenicity is likely a function of adaptation of this saprophytic organism to the environment. Genomic and epigenomic factors are implicated. I will sample the environment to define the diversity of the Vietnamese C. neoformans population and create a multilayered map in order to determine whether there is spatial clustering, and to identify the niche that VNIgamma occupies. I will use a macrophage model to determine the variability of pathogenicity within and between genotypes. I will use comparativ e genomics and RNAseq to test the validity of previously defined virulence factors and to define novel genetic and transcriptional differences that determine pathogenesis in the rabbit model of meningitis. These findings will be prospectively tested using RT-PCR in cerebrospinal fluid samples from human HIV infected and uninfected patients with cryptococcal meningitis.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 1443852
Applicant Surname Day
Approval Committee International Interview Committee
Award Date 2011-12-15T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title Intermediate Clinical Fellowship
Internal ID 097147/Z/11/Z
Lead Applicant Prof Jeremy Day
Partnership Value 1443852
Planned Dates: End Date 2017-12-31T00:00:00+00:00
Planned Dates: Start Date 2013-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Guy Thwaites, Prof John Perfect