Upon activation a T cell transitions from a state of semi-quiescence to a state of high activity. During the process of activation the T cell therefore needs to up regulate metabolic pathways to acquire the energy and nutrients required to facilitate the behavioural changes associated with its new functional state. If a cell fails to re programme its cellular metabolism this leads to defects in many different key effector functions such as migration, proliferation and cytokine production. Interestingly, it is also becoming clear that different subsets of T cells, such as regulatory T cells, Th1, Th2, Th17 and memory cells all express different metabolic signatures, implying that the nature of cellular metabolism specifies the effector or regulatory immune characteristics of the cell.
The aim of this project is to understand how key regulatory immune pathways rewire CD4+ T cell metabolism to suppress effector characteristics of T cells, dampening tissue-damaging inflammation. To address this aim, highly tractable in vitro assays will be used alongside complex in vivo models of inflammation, including malaria and helminth infections. The project will utilise cutting edge combinations of intravital two photon microscopy, transcriptomics, metabolic flux analyses and flow cytometry. Combined, these approaches will delineate the spectrum of action of key regulatory cytokines on effector T cell function, and will show how specific perturbation of metabolic events dominantly modifies T cell activity.
Training in immunology, microscopy, flow cytometry and systems biology will be provided to fit student’s background and interests. The student will join a team of interdisciplinary researchers who have established all of the experimental techniques required for the project. Dr Couper’s background is in malaria immunology, with a focus on in vivo and in vitro analysis of T cell function. Professor Grencis’s background is in helminth immunology, specifically how Th2 responses develop and are regulated. The core facilities at the University of Manchester will provide significant expertise in imaging, genomic technologies, and bioinfomatics.
The student will use and receive training in microscopy (two-photon and confocal), metabolic flux analyses (Seahorse analyser), transcriptomics and a variety of cutting edge immunological techniques, such as multiparameter flow cytometry. The student will also obtain training in in vivo experimentation.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk