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MRC DiMeN Doctoral Training Partnership: Understanding the burden of disease caused by the loss of TEX12 protein and its impact in cancer


   Faculty of Health and Life Science

  ,  Friday, January 13, 2023  Competition Funded PhD Project (Students Worldwide)

About the Project

Rare genetic conditions remain poorly understood resulting in limited treatment options. One such rare genetic condition is loss of TEX12, a recently discovered protein critical for fertility. Loss of TEX12, through mutations or gene deletion, is a rare event previously demonstrated to cause infertility. As TEX12 was reported to be exclusively meiotic, the general health of TEX12 null patients has not been previously investigated and infertility was assumed to be the only pathology. We have discovered that loss of TEX12 leads to female obesity and cerebellar hyperplasia in both sexes furthermore, we found that TEX12 plays a role in cancer development and progression and lack of TEX12 affects cancer predisposition. Consequently, following our discoveries, you will comprehensively investigate the consequences of TEX12 loss in patients utilising novel methodologies developed by our laboratory. This studentship offers a novel and unique translational model to study a rare genetic condition with importance for cancer biology in combination with clinical analysis. Our laboratories have identified a novel functional relationship between a TEX12 and cilia formation resulting in this project being at the forefront of research into this novel disease which will help determine the role of TEX12 as a ciliopathy related gene and proto-oncogene.

This interdisciplinary project will involve a unique breadth of training across two laboratories (see links below) 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/). This project is suited to students who need flexible working arrangements. We invite, welcome and champion applications from minority backgrounds. 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, DNA pull-downs followed by mass spectroscopy and cell-based models to understand disease pathology) 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, after the PhD. This project has been generously supported by the UK Medical Research Council and you will be supported by a Post-Doctoral Fellow working in the same field but on a distinct project. 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 is a collegial, supportive environment that champions talent, diversity and equity.

You will join our lab https://www.mcclurglab.com/ at the department of Biochemistry and Systems Biology (https://www.liverpool.ac.uk/systems-molecular-and-integrative-biology/about/biochemistry-systems-biology/) as a member of a supportive team of PhD students and Post-Doctoral scientists with similar interests, participating regularly in broad ranging group meetings and scientific symposia.

Primary Supervisor -

https://www.mcclurglab.com/urszula-mcclurg

https://www.cilianetwork.org.uk/people/umcclurg

Secondary supervisor –

https://medicinehealth.leeds.ac.uk/medicine/staff/694/dr-james-poulter

Informal enquiries can be made to Dr Urszula McClurg: 

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: https://www.dimen.org.uk/blog

Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply


Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: View Website
Studentships commence: 1st October 2023
Good luck!

References

Sou IF,…. McClurg UL. 2022. Cancer and meiotic gene expression: Two sides of the same coin? Current Topics in Developmental Biology https://www.sciencedirect.com/science/article/abs/pii/S0070215322000874
Sandhu S, …, McClurg UL. 2021. Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. Communications Biology, 8;4(1):1371. https://www.nature.com/articles/s42003-021-02887-4
Sou IF, .., Tee W-W, McClurg UL. 2021. Meiosis initiation: a story of two sexes in all creatures great and small. Biochemical Journal, 478(20), 3791-3805. https://portlandpress.com/biochemj/article/478/20/3791/230041/Meiosis-initiation-a-story-of-two-sexes-in-all

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