Defining the impact of T cell activation on the protective and migratory capacity of mucosal CD4+ T cells in tuberculosis


   Department of Respiratory Sciences

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  Prof A Cooper, Dr John Pearl  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional Supervisor: Dr Helen McGettrick, University of Birmingham

In this exciting joint PhD project between the University of Leicester (UoL) and the University of Birmingham (UoB), the student will join a collegiate international consortium investigating lung immunity to tuberculosis (TB) and driving innovation in the TB vaccine pipeline. Development of an effective vaccine is the single most effective tool to reduce the worldwide TB. The multi-million Euro consortium brings together fundamental immunologists, clinical specialists, experts in non-human primate models and vaccine developers and manufacturers. The student will investigate the fundamental aspects of immune protection using immunology, immunohistology, flow cytometry, bioinformatics analysis and will learn in vivo imaging and spatial transcriptomics. The project will focus on the the ability of T cells to undertake adhesion and migration into the lung of TB-infected mice (UoL). At UoB, multi-cellular in vitro models of leucocyte adhesion and migration will used to dissect the role of specific molecules in T cell migration. A unique aspect of this studentship is the ability to undertake in vitro and in vivo models in the context of complementary human and non-human primate data. This is a super opportunity because of the range of techniques and approaches, the networking and the potential for internationalization of the student’s experience.

Enquiries

Project Enquiries to [Email Address Removed].

Programme enquiries to [Email Address Removed]

To apply please refer to

https://more.bham.ac.uk/mrc-aim/phd-opportunities/


Biological Sciences (4) Chemistry (6) Engineering (12) Mathematics (25) Medicine (26)

Funding Notes

The competition funding provides students with:
4 years of stipend at UKRI rates
4 years of tuition fees at UK fee rates (Plus one award of a full overseas fee waiver to an international applicant)*
RTSG
Budget to help with the cost of purchasing a laptop
The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.

References

(1) Floyd, K, et al., Int J Tuberc Lung Dis 2018, 22, 723-730.
(2) Levin, M, et al., Lancet 2016, 387, 2268-2270.
(3) Chimen M*, McGettrick HM*, et al. Homeostatic regulation of T cell trafficking by a B cell-derived peptide is impaired in autoimmune and chronic inflammatory disease. Nat. Med 2015 21:467-474 PMID 25894827 * joint first author
(4) Stone, J.D., A.S. Chervin, and D.M. Kranz, T-cell receptor binding affinities and kinetics: impact T-cell activity and specificity. Immunology, 2009. 126(2): p. 165-76.
(5) Corse, E., R.A. Gottschalk, and J.P. Allison, Strength of TCR-peptide/MHC interactions and in vivo T cell responses. J Immunol, 2011. 186(9): p. 5039-45.
(6) Kaech, S.M., E.J. Wherry, and R. Ahmed, Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol, 2002. 2(4): p. 251-62.
(7) King, C.G., et al., T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology. Immunity, 2012. 37(4): p. 709-20.
(8) Keck, S., et al., Antigen affinity and antigen dose exert distinct influences on CD4 T-cell differentiation. Proc Natl Acad Sci U S A, 2014. 111(41): p. 14852-7.
(9) Kotov, D.I., et al., TCR Affinity Biases Th Cell Differentiation by Regulating CD25, Eef1e1, and Gbp2.
(10)Torrado, E., et al., Cooper AM. Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection. J Exp Med, 2015. 212(9): p. 1449-63.