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Investigating the mechanisms driving meiotic gene re-expression in cancer


Project Description

Meiosis is a specialised type of cell division which involves genome rearrangements. Many of the genes involved in meiotic homologous recombination are meiosis-specific however, they also constitute a latent toolbox of chromosome remodelling and recombination factors, which can be exploited by cancer cells. We found that synaptonemal complex (SC) proteins, normally involved in meiotic chromosome recombination, are re-expressed in many human cancers, with high expression levels correlating with aggressive disease. As SC proteins are absent in normal diploid cells, but highly expressed in many human tumours, they might offer specific, novel therapeutic targets and undoubtedly represent new potential diagnostic biomarkers.

However, the question of what chromatin states and gene expression regulators schedule the mitotic cell to re-express meiotic proteins remains unanswered. The student will spend year 1 in the Dr McClurg’s laboratory at the Institute of Integrative Biology in Liverpool IIB investigating the biology and cellular localisation of SC proteins re-expressed in cancer. Year 2 and 3 will be spend in Dr Tee’s laboratory in Singapore to investigate the chromatin stages and epigenetic factors associated with re-expression of meiotic proteins in cancer. This project will utilise an assortment of molecular tools to interrogate epigenetic changes correlated with meiotic gene re-expression (DNA and histone modifications, chromatin remodelling, as well as higher-order nuclear organisation) during cancer initiation and progression. The student will return to Liverpool for year 4 and identified factors will be validated as biomarkers and drug targets in cancer models followed by PhD write up.

Qualifications and Experience
You should have, or expect to hold, BSc (Hons) degree in a Biological or Biomedical Sciences related field, preferably with a first or upper second class grade. An additional Masters qualification would be an advantage. Experience or qualifications in molecular genetics and cell biology is especially desirable for this project.

This PhD studentship is funded for 4 years through an International Postgraduate Research Programme of the University of Liverpool and the A*STAR/ARAP programme of Singapore. The student will be placed at the University of Liverpool during years 1 and 4, and at the Institute of Molecular and Cell Biology (IMCB) in Singapore during years 2 and 3. Upon successful completion of the project a PhD will be awarded by the University of Liverpool.

Funding Notes

This PhD studentship is funded through an International Postgraduate Research Programme of the University of Liverpool and A*STAR/ARAP of Singapore.

Funding is for 2 years at standard RCUK stipend rate while working at the University of Liverpool (years 1 & 4), and for 2 years via the A*STAR/ARAP programme at their generous standard stipend rate while working in Singapore (years 2 & 3).

Tuition fees are covered at the UK Home/EU student rate (no tuition fees at Singapore).

Upon successful completion of the project a PhD will be awarded by the University of Liverpool. Applications from Home/EU students only.

References

1. Meiosis-like Functions in Oncogenesis: A New View of Cancer. McFarlane RJ, Wakeman JA. Cancer Res. 2017, 77(21):5712-5716.

2. Sandhu S, Salmon LJ, Hunter JE, Wilson CL, Perkins ND, Hunter N, Davies OR, McClurg UL (2019) A pseudo-meiotic centrosomal function of TEX12 in cancer. https://www.biorxiv.org/content/early/2019/01/02/509869
doi: https://doi.org/10.1101/509869

3. Hu Z, Tee WW (2017) Enhancers and chromatin structures: regulatory hubs in gene expression and diseases. Biosci Rep. 2017; 37(2). pii: BSR20160183. doi: 10.1042/BSR20160183

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