Combining genetics and high-resolution cell phenotyping to map pathways underlying inflammatory bowel disease (360G-Wellcome-208750_Z_17_Z)
Inflammatory bowel disease is a chronic, difficult to treat condition with unknown underlying causes. Given its high heritability, understanding IBD biology requires understanding how genetic risk variants impact the immune system. This project aims to identify measurable immune phenotypes through which IBD risk variants act, and investigate the impact of these phenotypes on disease prognosis. My first objective is to prioritize immune pathways where IBD genes are active, and develop methods of quantifying these pathways by phenotyping specific immune cells. I will use new statistical techniques to infer these pathways, single-cell analysis to discover impacted cell types, and collaborations with immunologists to establish phenotyping techniques. My second objective is to demonstrate associations between risk variants and candidate immune pathways. We will measure gene expression and readouts of immune function on IBD-associated cell types in 200 genotyped patients and 200 controls, and carry out eQTL, association and risk score analyses. My final objective is to build the groundwork for translating these discoveries into new treatments. We will test whether immune phenotypes predicted disease flares in our patients, and if so work with clinicians to design stratified medicine trials. We will work with partners to investigate future therapeutic interventions for these pathways.
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Grant Details
Amount Awarded | 1161290 |
Applicant Surname | Jostins-Dean |
Approval Committee | Sir Henry Dale Fellowship Interview Committee |
Award Date | 2017-10-18T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Sir Henry Dale Fellowship |
Internal ID | 208750/Z/17/Z |
Lead Applicant | Dr Luke Jostins-Dean |
Partnership Name | Royal Society/Wellcome Trust Sir Henry Dale Fellowship |
Partnership Value | 1161290 |
Planned Dates: End Date | 2024-03-29T00:00:00+00:00 |
Planned Dates: Start Date | 2018-01-08T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |
Sponsor(s) | Prof Fiona Powrie |