Linking human genotype and immunological phenotype to understand pathogenesis and improve treatment in tuberculosis (360G-Wellcome-206724_Z_17_Z)

£824,755

TB kills more people worldwide than any other infectious disease, yet its pathogenesis is still poorly understood which hinders therapeutic advances. The heterogeneity of immunological responses and clinical presentations make the investigation of the major determinants of outcome challenging. Host genetic variants regulate the immune response during infection, drive immunological pathogenesis of the disease, and can lead to poor outcomes. My aim is to link human genotype and immunological phenotype to better understand TB pathogenesis and thus improve TB treatment. The fellowship has three key goals: Investigate the impact of dexamethasone on transcriptional profiling of the immune response, bacterial clearance and survival/death in TB meningitis Determine whether LTA4H genotype can be used to predict inflammatory transcriptome and to identify additional genes associated with inflammatory transcriptome variation in TB meningitis Link human genotype and transcriptional immune responses associated with treatment failure or relapse in pulmonary TB To pursue these goals, I will use RNA-Seq to provide data on both human variants and whole-genome gene expression. These results will reveal the pathogenesis of different forms of TB, including pulmonary TB, meningeal and multi-drug resistant TB. Pathways associated with inflammasome and neutrophil-driven immunopathogenesis will be a particular focus.

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Grant Details

Amount Awarded 824755
Applicant Surname Thuong
Approval Committee International Interview Committee
Award Date 2017-06-19T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title International Intermediate Fellowship
Internal ID 206724/Z/17/Z
Lead Applicant Dr Nguyen Thuong
Partnership Value 824755
Planned Dates: End Date 2023-10-01T00:00:00+00:00
Planned Dates: Start Date 2017-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South East
Sponsor(s) Prof Guy Thwaites, Prof Michael Inouye