Maintenance and Metabolism of Intestinal ILC3s
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
The ultimate aim of the project is to understand what underlying factors may contribute to ILC3 heterogeneity with regards to how they are maintained in intestinal tissues as well as their metabolic capacity that may contribute to their maintenance and relate to potentially differing roles in inflammatory bowel disease.
The expected outcomes of this project are:
1. Dissecting the contribution of the bone marrow to ILC3 replenishment and maintenance.
2. Determining the differences in ILC3 subset responses both at steady state and in infection and immune-stimulatory models.
3. Investigating the metabolic heterogeneity of ILC3 subsets in healthy and diseased states to understand the role of metabolism in intestinal protection.
4. Identifying a supporting role of metabolism towards the maintenance of ILC3 subsets in healthy and diseased conditions.
The project will provide a strong training in in vivo immunology utilizing transgenic mice and models of infection and inflammatory disease. In particular, the successful candidate will utilize animal models (Citrobacter Rodentium infection, IL-2 complex treatment) to dissect how protective ILC3 responses in the intestines require different mechanisms to persist in vivo. Moreover, the candidate will utilize various molecular inhibitors to directly investigate the integral of key proteins important for both survival and metabolism of ILC3s to decipher the important requirements ILC3s demand to support effector functions and survival.
Finally, the candidate will have the opportunity to utilize a placement with the CASE partner AstraZeneca to translate findings in animals to human samples, utilising intestinal tissue samples taken from patients with inflammatory bowel disease to investigate ILC3 heterogeneity with the ultimate aim of informing future therapeutic strategies targeting ILC3 subsets. Further to this point, the student will benefit from the partners expertise in translational immunology and exposure to their drug discovery and clinical trials programmes, which have a core focus on immunotherapeutics.
The student will receive training in the Hepworth lab in multidimensional flow cytometry techniques, immunofluorescence imaging and other core techniques used in immunology including cell sorting, ELISA, RT-PCR, tissue culture and in vivo manipulation of the immune system. The project will also include training in microbiology including bacterial 16S sequencing and novel IgA-seq techniques aimed at dissecting host responses against bacteria in the intestines.
The expected outcomes of this project are:
1. Dissecting the contribution of the bone marrow to ILC3 replenishment and maintenance.
2. Determining the differences in ILC3 subset responses both at steady state and in infection and immune-stimulatory models.
3. Investigating the metabolic heterogeneity of ILC3 subsets in healthy and diseased states to understand the role of metabolism in intestinal protection.
4. Identifying a supporting role of metabolism towards the maintenance of ILC3 subsets in healthy and diseased conditions.
The project will provide a strong training in in vivo immunology utilizing transgenic mice and models of infection and inflammatory disease. In particular, the successful candidate will utilize animal models (Citrobacter Rodentium infection, IL-2 complex treatment) to dissect how protective ILC3 responses in the intestines require different mechanisms to persist in vivo. Moreover, the candidate will utilize various molecular inhibitors to directly investigate the integral of key proteins important for both survival and metabolism of ILC3s to decipher the important requirements ILC3s demand to support effector functions and survival.
Finally, the candidate will have the opportunity to utilize a placement with the CASE partner AstraZeneca to translate findings in animals to human samples, utilising intestinal tissue samples taken from patients with inflammatory bowel disease to investigate ILC3 heterogeneity with the ultimate aim of informing future therapeutic strategies targeting ILC3 subsets. Further to this point, the student will benefit from the partners expertise in translational immunology and exposure to their drug discovery and clinical trials programmes, which have a core focus on immunotherapeutics.
The student will receive training in the Hepworth lab in multidimensional flow cytometry techniques, immunofluorescence imaging and other core techniques used in immunology including cell sorting, ELISA, RT-PCR, tissue culture and in vivo manipulation of the immune system. The project will also include training in microbiology including bacterial 16S sequencing and novel IgA-seq techniques aimed at dissecting host responses against bacteria in the intestines.