Epithelial tissues are positioned at the interface between internal and external environments where they play a key role in the fight against pathogens, both directly through innate defence mechanisms and indirectly by modulating immunocyte phenotype and activation states. This interplay is critical for supporting healthy tissue homeostasis as it helps balance surveillance mechanisms involved in eliminating pathogens and/or mutated cells against the need to limit inflammation. In this way, the epithelium is able to prevent cancer development and to dampen or resolve inflammation.
Through this project, you will develop a novel experimental 3D coculture system to study immune: epithelial cell interactions and investigate the role of the cellular environment in modulating inflammation and epithelial barrier function and repair.
The aims are to investigate reciprocal mechanisms of a) normal human epithelial cells on immune cell phenotype and activation status and b) the impact of immunocyte signalling (including cytokines) on urothelial tissue homeostasis as a regenerative barrier epithelium. Using preliminary findings, the starting hypothesis is that PPARγ ligands produced endogenously by differentiated human urothelium provide a natural inflammation-suppressive or -resolving environment.
This cutting-edge project will be a multidisciplinary collaboration between the labs of the supervisors, using single-cell sequencing (10x Multiome) and immunological deep-phenotyping imaging (Nanostring DSP) to understand the immune populations present. The student will have access to world-class facilities in the Biology Technology Facility & expert technical assistance and training providing unrivalled training opportunities in cellular and molecular biology, in vitro experimentation and live cell imaging, immune and epithelial cell phenotyping and lipidome mass-spectrometry. The project is 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 WR DTP and the University of York are committed to recruiting 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 we 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.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 1st October 2022 (the student will be affiliated with the Department of Biology)
Shortlisted candidates will be interviewed in mid February 2022