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