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  Why do cancers cells re-express meiotic SYCP1 protein?


   Institute of Systems, Molecular and Integrative Biology

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The aim of meiosis is to generate gametes by recombining the chromosomes and reducing the genome from diploid to haploid. However, in mitosis haploid genome and recombination have catastrophic, oncogenic outcomes. Consequently, the process of somatic cell division requires the accurate and specific silencing of meiotic genes when cells transition to mitosis. Interestingly, failure of this silencing occurs in approximately 15% of human cancer patients who re-express the meiotic SYCP1 protein. We find that SYCP1 re-expression is induced by common chemotherapy treatments causing DNA damage induction. The process of meiotic recombination involves similar mechanisms to DNA double strand break repair (DSBR) and due to this similarity SYCP1 re-activation in cancer cells may contribute to genome instability. In this project you will investigation potential mechanisms driving SYCP1 re-expression in cancer. You will investigate the biology of SYCP1 re-expression in cancer, the effect it has on cellular physiology and response to chemotherapeutics.

This interdisciplinary project will involve a unique breadth of training with complementary approaches utilising our world-class facilities including cell biology, proteomics (https://www.liverpool.ac.uk/pfg/), genetics (https://www.liverpool.ac.uk/genomic-research/) and imaging (https://cci.liv.ac.uk/). During this interdisciplinary project you will develop a unique combination of skills in pathology, cell biology, big data, proteomics, genetic and imaging techniques. A broad range of inter-disciplinary approaches (CRISPR-Cas9 genome editing and DNA pull-downs followed by mass spectroscopy) will help you develop diverse technical expertise. Furthermore, this multi-disciplinary training will give you a broad range of skills allowing a wide choice of career options, both within and outside of academia. Our group is committed to supporting the development of early career researchers. Successful candidate will not only join a vibrant department but will also be supported in attending national and international conferences as well as undertaking training to further develop and pursue their own career development. Our laboratory https://www.mcclurglab.com/  is a collegial, supportive environment that champions talent, diversity and equity.

The project is suited to a student with at least a good Masters (Upper Second Class in Biological or Life Sciences). Please apply by emailing Dr Urszula McClurg at .


Biological Sciences (4)

Funding Notes

The project is open to both European/UK and International students. It is UNFUNDED and applicants are encouraged to contact Dr Urszula McClurg directly to discuss their application and the project.
Assistance will be given to those who are applying to international funding schemes.
The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £ 5,000 per year.
New self-funded applicants may be eligible for a tuition fees bursary (UK applicants only) or a £2000 ISMIB Travel and Training Support Grant.
Details of costs can be found at liverpool.ac.uk/study/postgraduate-research/fees-and-funding/fees-and-costs/

References

Cancer and meiotic gene expression: Two sides of the same coin?
Sou, I. F., Hamer, G., Tee, W. -W., Vader, G., & McClurg, U. L. (2023). Current Topics in Developmental Biology (Vol. 151, pp. 43-68). doi:10.1016/bs.ctdb.2022.06.002
Meiosis initiation: a story of two sexes in all creatures great and small
Sou, I. F., Pryce, R. M., Tee, W. -W., & McClurg, U. L. (2021). BIOCHEMICAL JOURNAL, 478(20), 3791-3805. doi:10.1042/BCJ20210412
Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12
Sandhu, S., Sou, I. F., Hunter, J. E., Salmon, L., Wilson, C. L., Perkins, N. D., . . . McClurg, U. L. (2021). COMMUNICATIONS BIOLOGY, 4(1). doi:10.1038/s42003-021-02887-4

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