Age-related disease: Fidelity mechanisms that protect against epigenetic decay

About the Project

Lead supervisor:Prof Dawn Coverley

Co-supervisors:Dr Andrew Mason

The student will be registered with the Department of Biology

Inside the mammalian cell nucleus DNA and associated proteins are spatially organised and differentially compacted, so that some genes are accessible and some are not. Nuclear disorganisation and degradation of chromatin structure is associated with loss of control over cell identity, and is intrinsically linked with cancer and other age-related pathologies. The CIZ1 protein forms long non-coding RNA-dependent protein assemblies at specific nuclear locations that help to lock cell-type specific nuclear configurations. We routinely study two parts of the CIZ1 protein, which in normal cells are co-located in nuclear assemblies. However, in breast cancer cells they are disrupted, assemblies are abnormal and large parts of specific chromosomes are deprotected, driving changes in the expression of genes linked with cancer. This can be probed bioinformatically, despite no mutational profile, enabling a project to establish the extent to which this novel mechanism allows cells to escape their programming and predispose to transformation. The student will take a multi-pronged approach, benefitting from the skill sets of two labs. i) Establish a streamlined bioinformatic pathway to probe The Cancer Genome Atlas and other publicly available data sets, across a range of human cancer types in order to test how widely the principles uncovered in breast cancers can be applied, with initial focus on bladder cancer. ii) Explore publicly available normal aging transcriptome series, to establish the extent to which the changes associated with early-stage breast cancers, may predate the tumour. iii) Generate new long-read transcriptomes using Oxford Nanopore sequencing technology to identify interfering transcript species. iv) Use high-resolution fluorescence microscopy, and protein expression approaches, to model the effect of non-genetic changes in CIZ1 linked with bladder cancer on CIZ1 chromatin shield function. Other approaches can be accommodated depending on the needs of the project and the preference of the student.

Sofi, S. et al. Prion-like domains drive CIZ1 assembly formation at the inactive X chromosome. J Cell Biol 221 (2022).

Turvey, G.L. et al. Epigenetic deprogramming by disruption of CIZ1-RNA nuclear assemblies in early-stage breast cancers. J Cell Biol 224 (2025).

The University of York is 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.

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.

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 Biomedical Science (3 year)

Start Date: 21 September 2026