WR DTP project: Does reciprocal crosstalk between epithelium and immunocytes contribute to urothelial tissue homeostasis?

"Epithelial tissues are positioned at the interface between internal and external environments where they play a role in the fight against pathogens, both directly through innate defence mechanisms and indirectly by modulating immunocyte phenotype and activation. This interplay supports healthy tissue homeostasis by balancing effective surveillance and elimination of pathogens/mutated cells, against an equally effective dampening or resolution of inflammation, thereby serving to prevent either the development of cancers or chronicity of inflammatory states.

This project will develop a new experimental coculture system to study immunocyte:epithelial cell interactions and investigate the role of the local paracrine environment in modulating inflammation and epithelial barrier function. It will make use of a well-characterised normal human uro-epithelial cell culture system that can be induced to differentiate on membranes for introduction of immunocyte populations basally.

The aims will be to investigate reciprocal influences of a) urothelial cells on immunocyte phenotype and activation status and b) the impact of immunocyte signalling (including cytokines) on urothelial tissue homeostasis as a regenerative barrier epithelium. Normal urothelial differentiation is dependent on activation of nuclear receptor PPARγ, whilst in immune cells, PPARγ is reported to transrepress proinflammatory gene expression. This supports the starting hypothesis that PPARγ ligands produced endogenously by the urothelium provide a natural inflammation-suppressive or -resolving environment.

This project will provide training in cellular and molecular biology, in vitro experimentation and live cell imaging, immune and epithelial cell phenotyping, transcriptomics and lipidomics. The project will be suitable for a graduate in Biomedical Sciences, Biochemistry, Biology or related subjects with a strong interest and background knowledge of cancer biology and/or immunology. "

The White Rose DTP in Mechanistic Biology is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.