Immune reactions against pathogens and tumours require several layers of control to safeguard the appropriate management of infectious agents and cancerous cells without inducing excessive tissue damage or inflammation. Peripheral neurons establish a reciprocal molecular and signalling dialogue with immune cells, and this conversation can significantly and critically impact the result of immune responses. However, our understanding of how this neuroimmune crosstalk is regulated is still superficial.
This project seeks to explore and determine the cellular and molecular elements that constitute the neuroimmune crosstalk at mucosal tissues during homeostasis and immune reactions. The project will prioritise the study of the female reproductive tract, a mucosal tissue critical for the evolutive survival of mammalian species that has been understudied. A major aim is to investigate the neuronal circuits implicated in this neuroimmune crosstalk at the level of the peripheral and central nervous system.
The PhD student leading the project will implement transgenic mouse strains, mouse models of microbial infection and/or tumorigenesis, and precise targeting of sensory and motor neurons to define and dissect the neuroimmune cellular axes and molecular signalling pathways impacting immune system homeostasis and immunity. The project will involve developing and characterising new genetically-modified mouse strains and using multidisciplinary approaches to study the neurons innervating mucosal tissues. Additionally, immune cells, with particular focus on lymphocytes, will be extensively characterise by high-dimensional flow cytometry, omics analysis, and in vivo and in vitro approaches. Newly uncovered cellular and molecular pathways will be functionally characterised and perturb to study their impact in cancer and microbial infections.
We expect that the results derived from this project will aid in our understanding of neuro-immune homeostasis, and lead to exciting discoveries at the physiological and molecular level.
References
Gogoi, M., Clark, P.A., Ferreira, A.C.F., Rodriguez, N.R., Heycock, M., Ko, M., Murphy, J.E., Chen, V., Luan, S., Jolin, H.E., McKenzie, A.N.J. (2024)
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