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Stopping brain tumours in their tracks – the role of RhoGTPase activating proteins (ARHGAPs) in glioma cell migration and invasion

About This PhD Project

Project Description

Six new fully funded PhD research studentships are offered in the School of Applied Sciences for a 23 September 2019 start. The School is made up of the Departments of Biological and Geographical Sciences, Chemical Sciences and Pharmaceutical Sciences.

There is competition funding for 6 of the 12 research projects advertised. Usually the projects which receive the best applicants are funded.

Successful applicants will receive a fully funded PhD opportunity to investigate one of the deadliest cancer types, Glioblastoma, for improved treatment targeting the migratory potential of these tumours.

One of the hallmarks of cancer is cell migration and invasion, a prerequisite for tumour metastasis. Targeting the mechanisms controlling cell migration and invasion offers a unique opportunity to improve treatment of one of the most invasive and highly migratory brain tumours such as Glioblastoma (GBM) and to enhance our understanding of tumour cell migration and invasion.
GMB remains one of the most difficult to treat cancers affecting both adults and children. Even after combination treatment of surgery, radiotherapy and chemotherapy average survival is 12-18 months. Targeting the infiltrative nature of these tumours is one of 10 identified research priorities in brain tumour research and our recent research has indicated an important role for the RhoGTPase activating proteins (ARHGAPs) in glioma cell migration and invasion. The ARHGAPs are regulators of the RhoGTPases including RhoA, Rac1 and CDC42, all molecules directly involved in cell migration dynamics. We recently identified members of the ARHGAP gene family to be key regulators of cell migration and invasion in brain tumour cells. We demonstrated clinical relevance for ARHGAP expression in Glioblastoma patients underlining the importance of research into the role of the ARHGAPs in brain tumour dissemination. So far, we have defined anti- or pro-migratory roles for two ARHGAPs (ARHGAP 12 and 29) but the role of the other candidate ARHGAP genes is still unknown.

This PhD studentship will define the roles of various members of the ARHGAP gene family in glioma cell migration/invasion in glioma cells. We will determine downstream effects of suppressing or overexpressing the ARHGAPs on their effectors RhoA, Rac1 and CDC42. We will also investigate the effects of hypoxia, which is reported to promote glioma cell migration and invasion, on the expression of the different ARHGAPs (incl. ARGHGAPs 12 & 29) and their potential as anti-migratory cellular targets including towards typically chemoresistant migratory hypoxic cells.

It is anticipated that the outcome of this PhD will reveal molecular details that will aid the design of novel inhibitors targeting the migratory potential of glioma cells and identify molecular subtypes to improve patient treatment selection.

The PhD student will have the opportunity to acquire various laboratory skills including:
2D and 3D in vitro culture of established and patient derived cell lines, gene silencing, Western blotting, PCR, migration/invasion assays, confocal microscopy and live cell imaging and the use of a hypoxia inducible system.
In addition we have strong collaborative links with research groups in the UK, Europe and the USA (Harvard University) and depending on results within the first two years of the studentship there will be an opportunity for a research visit to our collaborators at Harvard. We expect the PhD student to present his/her research findings at at least one neuro-oncology scientific meeting.

The studentships are open to citizens of the UK or EU only, and cover the full cost of tuition fees and an annual tax-free bursary of £15,009 for three years (RCUK rates). Successful applicants will have a very good first or upper second degree or Masters degree in a relevant subject. The course will begin in September 2019.

To apply, please send your CV and a personal statement to . Please indicate that you wish to apply for the project above and highlight Dr Anke Brüning-Richardson, as the supervisor. Please note that the deadline for applications is 25 April 2019.

Please contact Dr Anke Brüning-Richardson, email: for enquiries on the project.

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