Evolution of Burkholderia pseudomallei and its disease dynamics. (360G-Wellcome-107376_Z_15_Z)

£250,000

Burkholderia pseudomallei is a soil organism found in many parts of the world. Through direct contact with contaminated soil/water, humans acquire infection and develop melioidosis. The disease, often fatal, displays broad clinical manifestations, with different disease patterns reported from different countries. Little is known about factors influencing the disease outcomes and its geographical signatures. We hypothesise that bacterial genetics contribute to disease outcomes, and specificity th at (i) bacterial factors impact on acquisition, disease manifestations and severity; and that (ii) the prevalence of such factors are not homogenously distributed in bacterial populations in different endemic areas. A total of 985 B. pseudomallei whole genome sequences will be employed to address these hypotheses. A phylogeny constructed from 204 global isolates will highlight geographically distinct lineages and their evolutionary timeline. Routes of infection and progression to disease will be related to genetic relatedness of 331 disease and 450 environmental isolates collected from a circumscribed area in Thailand. Clinical manifestations linked to disease isolates will allow us to identify bacterial genetic factors associated with disease specificity, as to consider their prevalence in other geographical locations. Genetic variants predicted in silico will be tested in the zebrafish embryo infection model to validate computational hypotheses.

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Grant Details

Amount Awarded 250000
Applicant Surname Chewapreecha
Approval Committee Basic Science Interview Committee
Award Date 2015-04-13T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Sir Henry Wellcome Postdoctoral Fellowship
Internal ID 107376/Z/15/Z
Lead Applicant Miss Kamolchanok Chewapreecha
Partnership Value 250000
Planned Dates: End Date 2019-05-31T00:00:00+00:00
Planned Dates: Start Date 2015-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Gordon Dougan, Prof Nicholas Day, Prof Sharon Peacock