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Self-funded project: Functional analysis of CIZ1


Department of Biology

About the Project

Application accepted for either MSc by Research or PhD.

We are interested in the structure, function and disease implications of the CIZ1 protein, and related factors involved in organisation of the mammalian cell nucleus. Recent work has focussed on its interaction with Xist long non-coding RNA 1 2, and its role in the maintenance of chromatin modifications at the inactive X chromosome (Xi) 3. This project will continue to exploit Xi as a model system and explore the interaction between CIZ1 and regulatory factors that modulate it’s function in the cell cycle. The goal is to understand the impact of changes in CIZ1 that are common in human cancers 4 5, and to assess the extent to which these destabilise epigenetic state in early stage tumours. Core techniques will be mammalian cell culture and synchronisation, molecular biology techniques to generate expression vectors, immunofluorescence microscopy and quantitative image analysis. Further opportunities exist for transcriptomic analysis or biochemical approaches, depending on interests and the needs of the project.

1. Ridings-Figueroa, R. et al. The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Genes Dev 31, 876-888 (2017).
2. Sunwoo, H., Colognori, D., Froberg, J.E., Jeon, Y. & Lee, J.T. Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proc Natl Acad Sci U S A 114, 10654-10659 (2017).
3. Stewart, E.R. et al. Maintenance of epigenetic landscape requires CIZ1 and is corrupted in differentiated fibroblasts in long-term culture. Nat Commun 10, 460 (2019).
4. Higgins, G. et al. Variant Ciz1 is a circulating biomarker for early-stage lung cancer. Proc Natl Acad Sci U S A 109, E3128-3135 (2012).
5. Rahman, F.A., Aziz, N. & Coverley, D. Differential detection of alternatively spliced variants of Ciz1 in normal and cancer cells using a custom exon-junction microarray. BMC Cancer 10, 482 (2010).

The Department of Biology at the University of York 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.

Funding Notes

This is a self funded research project. Applicants need to have adequate funds to meet the costs of a self-funded research project including tuition fees and living expenses for the duration of the research programme.

References

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.

START DATE: 1st October 2021

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