Human Immune Response Variation in Tuberulosis (360G-Wellcome-207511_Z_17_Z)
I aim to discover novel mechanisms by which differences in human immune responses influence the outcome of Mycobacterium tuberculosis (Mtb) infection. I hypothesise that host-genetic polymorphisms lead to variation in immune responses that determine the clinical outcome of Mtb infection by affecting host-cell restriction of mycobacterial growth. We will use transcriptional profiling at the site of tuberculin skin tests (TST) to make comprehensive molecular and systems level assessments of in vivo human immune responses to a standardised mycobacterial challenge. In order to identify human immune responses that increase risk of disease in people exposed to Mtb, we will test the hypothesis that the TST transcriptome will reveal immune phenotypes associated with progression of LTBI to active TB. We will test the role of host genetics by identifying genome-wide expression quantitative trait loci (eQTL) associated with variation in the TST transcriptome. We will then recall participants by genotypes associated with selected traits to undertake in vitro mechanistic studies in primay immune cells. We will validate the causal association between genetic and phenotypic variations, and test their impact on Mtb restriction by macrophages. The findings will inform clinical risk stratification, vaccine design and development of host directed therapies for TB.
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 | 1660537 |
Applicant Surname | Noursadeghi |
Approval Committee | Science Interview Panel |
Award Date | 2017-07-11T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | Investigator Award in Science |
Internal ID | 207511/Z/17/Z |
Lead Applicant | Prof Mahdad Noursadeghi |
Partnership Value | 1660537 |
Planned Dates: End Date | 2024-06-04T00:00:00+00:00 |
Planned Dates: Start Date | 2018-06-04T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |