Lead supervisor: Prof Dawn Coverley (Department of Biology)
Co-supervisor: Prof Jenny Southgate (Department of Biology)
The student will be registered with the Department of Biology
The epithelium that lines the bladder (urothelium) is a quiescent tissue with huge regenerative capacity. Using normal human urothelial cells we can reconstruct, in the culture dish, the processes by which urothelium expands and differentiates to form a barrier, as well as its reentry into the cell cycle to enable regeneration following injury. This well-defined human experimental model will be used to study the expression and function of the nuclear matrix protein CIZ1. CIZ1 is implicated in the maintenance of epigenetic state, specifically the preservation of three histone-post translational modifications associated with gene repression, and has been most extensively studied in the context of the inactive X chromosome in female mammals. It is a complex gene with multiple alternatively spliced variants which modulate the ability of its intrinsically disordered domains to coalesce around chromatin. This project will profile CIZ1 splice variant diversity at protein and transcript level, across well-characterised transitions in cell state to reveal fundamental mechanistic information about how states are fixed at the level of nuclear organization. The studentship will span two neighbouring labs with complementary expertise, and will involve primary human cell culture, gene transduction, tissue regeneration and differentiation, transcriptome and protein level analysis, quantitative microscopy, and bioinformatics. The student will have access to a very well-equipped Bioscience Technology Facility and specialist staff in the Department of Biology at the University of York, and be able to draw on a bank of tools, reagents and data sets already available in the host labs. This timely opportunity to apply new knowledge derived from developmental studies in mouse into an important human context, has the potential to yield significant new and exploitable insight into the plasticity of transition states .
For recent information on CIZ1: Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome. Sofi S, Williamson L, Turvey GL, Scoynes C, GodwinJ, Brockdorff N, Ainscough J, Coverley D. J Cell Biol. 2022 Apr 4;221(4):e202103185.
For capabilities of the bladder epithelial cell model: Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder. Hinley J, Duke R, Jinks J, Stahlschmidt J, Keene D, Cervellione RM, Mushtaq I, De Coppi P, Garriboli M, Southgate J. Am J Pathol. 2022 Jun;192(6):943-955.
The Department of Biology holds an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.
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 any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 1st October 2023
Interviews: Friday 10 February 2023 or Monday 13 February 2023. Please keep these dates free.