Glioblastoma is the most lethal brain cancer in adults. Its poor prognosis is a result of aggressive tumour growth, therapeutic resistance, and tumour heterogeneity at the cellular and genetic level. These characteristics are linked to a subpopulation of glioblastoma cancer stem cells in that drive heterogeneity and tumour recurrence after therapy. How glioblastoma cancer stem cells maintain their stemness is incompletely understood, but this is an important process relevant for glioblastoma progression. We have previously shown that the transcription factor ZEB1 is a key regulator of stem cell traits in glioblastoma (e.g. Siebzehnrubl et al. EMBO Mol Med 2013, Jimenez-Pascual et al. Cancer Disc 2019). Recently, we have found that ZEB1 regulates asymmetric division of normal stem cells in the brain (Gupta et al. Cell Rep 2021). Thus, it is possible that glioblastoma cancer stem cells retain their stem cell phenotype through asymmetric division and this process is mediated by ZEB1. This project will investigate asymmetric division as a mechanism of cancer stem cell maintenance in glioblastoma and how this is regulated at the molecular level, using in vitro and in vivo models. We will use live cell imaging of patient-derived glioblastoma cell cultures to quantify rates of asymmetric division. Genetic targeting of ZEB1 and candidate downstream effectors will demonstrate their role in regulating asymmetric cell division. We will use xenograft models to evaluate the importance of candidate regulators of asymmetric cell division for cancer stem cell maintenance and tumour progression.
Please note that this project can be studied as a PhD or MPhil.
A 1st or Upper 2nd class UK honours degree or equivalent. Please visit School of Biosciences Postgraduate Research for more details.
For those whose first language is not English, IELTS with an overall score of 6.5 with 5.5 in all subskills, or equivalent. Please see our English Language Requirements guidance for more details.
How to Apply
To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy), Mode of Study (Full Time) and Start Date (this can be flexible as it is a self-funded project). This will take you to the application portal.
Candidates must submit the following:
• Supporting statement
• Qualification certificates
• Proof of English language (if applicable)
In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, specify that you will be self-funding. If you are applying for more than one Cardiff University project with the same entry intake, please note this in the research proposal section as the form only allows you to enter one title.