About the Project
CD4+ T cells are essential components of the immune system, orchestrating protection against infection. The immunological and stromal cues within tissues that ensure the appropriate diversification of effector CD4+ T cell subtypes to coordinate protection and establishment of long-lived immunological memory are, however, poorly understood.
In this project the student will dissect the spatiotemporal processes underlying effector CD4+ T cell diversification during an immune response, using malaria as a model infection. Malaria, caused by Plasmodium spp. of parasites is a complex infection where multiple CD4+ T cell subsets are critical for protection. The student will utilise high dimensional imaging mass cytometry to analyse where effector CD4+ T cell subpopulations – characterised in multi-parameter detail based on differentiation and functional signatures - compartmentalise and how they engage with distinct stromal and immune cell populations, during the course of infection. The student will subsequently analyse how chemokine cues choreograph CD4+ T cell positioning within the identified tissue niches and control CD4+ T cell engagement with other cell types to appropriately tune the CD4+ T cell differentiation programme and specify effector function during infection.
The successful candidate will receive training in various cutting edge immunological techniques including imaging mass cytometry, spectral flow cytometry, confocal and immunofluorescence microscopy, all combined with in vivo training. Thus, the successful candidate will obtain essential interdisciplinary and quantitative in vivo skills to support their future career.
Training/techniques
The successful candidate will receive training in various cutting-edge immunological techniques. Associated with this work will be the development of excellent in vivo skills in infection modelling as well as in vitro use of cellular activation, migration and adhesion assays. The student will receive training in cutting edge flow cytometry, confocal imaging and microscopy and imaging mass cytometry.
The student will become proficient in quantitative analyses of high-dimensional images, which will require developing expertise in statistics and computation. The student will utilise a number of existing RNA-seq libraries in their studies, providing experience and training in bioinformatics.
Thus, the successful candidate will obtain essential interdisciplinary and quantitative in vivo skills to support their future career. The student will be embedded within the wider immunology groups at the University, which will provide the student with outstanding further opportunities to increase their wider knowledge of immunology to develop their project through expert collaborations.
Entry requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Biology, Immunology or a related subject.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
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 Immunology.
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 https://www.bmh.manchester.ac.uk/study/research/programmes/integrated-teaching/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.
If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk.
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/
Funding Notes
References
Haley, M. J., Bere, L., Minshull, J., Georgaka, S., Garcia Martin, N., Howell, G., Coope, D., Roncaroli, F., King, A., Wedge, D. C., Allan, S. M., Pathmanaban, O. N., Brough, D. & Couper, K. N., 1 Apr 2024, (Accepted/In press) In: Science Advances.
The comparable tumour microenvironment in sporadic and NF2-related schwannomatosis vestibular schwannoma
Gregory, G. E., Jones, A. P., Haley, M. J., Hoyle, C., Zeef, L. A. H., Lin, I-H., Coope, D. J., King, A. T., Evans, D. G., Paszek, P., Couper, K. N., Brough, D. & Pathmanaban, O. N., 21 Jul 2023, In: Brain Communications. 5, 4, fcad197.
Memory CD8+ T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections.
Shaw TN, Haley MJ, Dookie RS, Godfrey JJ, Cheeseman AJ, Strangward P, Zeef LAH, Villegas-Mendez A, Couper KN.Immunology. 2021 Dec;164(4):737-753. doi: 10.1111/imm.13405. Epub 2021 Aug 27
Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors.
Gray AL, Karlsson R, Roberts ARE, Ridley AJL, Pun N, Khan B, Lawless C, Luís R, Szpakowska M, Chevigné A, Hughes CE, Medina-Ruiz L, Birchenough HL, Mulholland IZ, Salanga CL, Yates EA, Turnbull JE, Handel TM, Graham GJ, Jowitt TA, Schiessl I, Richter RP, Miller RL, Dyer DP.Cell Rep. 2023 Jan 31;42(1):111930. doi: 10.1016/j.celrep.2022.111930. Epub 2023 Jan 5.
Analysis of combinatorial chemokine receptor expression dynamics using multi-receptor reporter mice.
Medina-Ruiz L, Bartolini R, Wilson GJ, Dyer DP, Vidler F, Hughes CE, Schuette F, Love S, Pingen M, Hayes AJ, Fu J, Stewart AF, Graham GJ.Elife. 2022 Jun 14;11:e72418. doi: 10.7554/eLife.72418
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