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Understanding the biology of TEX12 as a centrosomal protein


Project Description

All cells have to divide to ensure the survival of the organism. There are two main types of cellular division, meiosis and mitosis. For reproduction, cells divide through a specialised process called meiosis which produces cells with half the genetic material. Somatic cells divide by mitosis, where genetic material is maintained at a double copy level and two daughter cells are produced. In mitosis centrosomes play a critical role in organising microtubules and providing polarity required for cellular division. It was previously believed that meiosis differs from mitosis in that centrosomes dissipate in prophase of meiosis in mouse oocytes accompanied by the loss of centrioles and formation of multiple pericentriolar material-containing microtubule organising centres that are involved in spindle assembly
instead. However, recent studies reported that centriole remnants persist in fully grown oocytes. Similarly, we identified centrin-rich clusters at all stages of the meiotic oocyte division. This question is of critical importance as presence of centrosome-like structures in meiosis would not only change our understanding of this process but would also help us understand how first mitotic centrosomes are
created. We have identified a novel protein, previously believed to be exclusively meiotic, to be present in both centrosome-like structures in meiosis but also in mitotic centrosomes. This PhD will focus on defining this novel observation and determining the role of meiotic centrin rich bodies in development.

HOW TO APPLY

Applications should be made by emailing with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the project and the University. Applications not meeting these criteria will be rejected.

In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to . A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to

Funding Notes

This is a 3.5 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The project will start ASAP. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.

References

Salmon LJ, Sandhu S, Pastok MW, Wilson CL, Hunter JE, Perkins ND, Jennings C, Hunter N, Davies OR,
McClurg UL (2019) Meiotic TEX12 is a novel centrosomal protein controlling fidelity of chromosome
division in cancer cell. Manuscript submitted

Papini D, Langemeyer L, Abad MA, Kerr A, Samejima I, Eyers PA, Jeyaprakash AA, Higgins JMG, Barr FA,
Earnshaw WC. TD-60 links RalA GTPase function to the CPC in mitosis. Nature Communications 2015, 6,
7678

Zhou L, Tian X, Zhu C, Wang F, Higgins JMG. Polo-like kinase-1 triggers histone phosphorylation by
Haspin in mitosis. EMBO Reports 2014, 15, 273-281

Wang F, Ulyanova NP, Daum JR, Patnaik D, Kateneva AV, Gorbsky GJ, Higgins JMG. Haspin inhibitors
reveal centromeric functions of Aurora B in chromosome segregation. Journal of Cell Biology 2012,
199(2), 251-268

Nabbi A*, McClurg UL*, Thalappilly S, Almami A, Mobahat M, Bismar TA, Binda O, Riabowol K (2017)
ING3 promotes prostate cancer growth by activating the androgen receptor BMC Medicine 2017,
15(1):103-125

McClurg UL, Cork DMW, Darby S, Ryan-Munden CA, Mendes-Cortes L, Gaughan L, Robson CN (2017)
Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity.
Nucleic Acids Research 2017, 45(4): 1793-1804

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