About the Project
Regulation of the immune system is fundamental to protecting the host from infection whilst also constraining inappropriate responses that may lead to autoimmunity and undesirable inflammation and immunopathology.
Innate lymphoid cells (ILCs) localise predominantly at mucosal surfaces where they act as critical innate sentinels for tissue damage and infection. ILC2s were discovered recently as significant new participants in type-2 immune regulation (asthma and allergic responses), playing critical roles at the interface of innate and adaptive immunity.
ILCs selectively express receptors for neurotransmitters and neuropeptides, and their interactions with the nervous system during homeostasis and infection have been reported recently. We wish to develop new models to investigate the functional importance of ILC-expressed neuro-regulators in inflammation and immunity.
The student will gain skills in immunology, whole organism physiology (an MRC skill priority), transgenesis, flow cytometry, single cell analysis - RNAseq, CRISPR/Cas9 techniques, bioinformatics.
References
Halim TYF, Rana BMJ, Walker JA, Kerscher B, Knolle MD, Jolin HE, Serrao EM, Haim-Vilmovsky L, Teichmann SA, Rodewald HR, Botto M, Vyse TJ, Fallon PG, Li Z, Withers DR, McKenzie ANJ. (2018)
Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells.
Immunity 19;48(6):1195-1207.
Walker JA, McKenzie ANJ. (2018)
TH2 cell development and function.
Nat Rev Immunol. 18(2):121-133.
Cardoso V, Chesné J, Ribeiro H, García-Cassani B, Carvalho T, Bouchery T, Shah K, Barbosa-Morais NL, Harris N, Veiga-Fernandes H. (2017)
Neuronal regulation of type 2 innate lymphoid cells via neuromedin U.
Nature 549(7671):277-281 doi: 10.1038/nature23469. PMID: 28869974
Moriyama S, Brestoff JR, Flamar AL, Moeller JB, Klose CSN, Rankin LC, Yudanin NA, Monticelli LA, Putzel GG, Rodewald HR, Artis D. (2018)
β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.
Science 359(6379):1056-1061
Sui P, Wiesner DL, Xu J, Zhang Y, Lee J, Van Dyken S, Lashua A, Yu C, Klein BS, Locksley RM, Deutsch G, Sun X. (2018)
Pulmonary neuroendocrine cells amplify allergic asthma responses.
Science 360(6393).
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