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Role of centriolar proteins in invasion

Primary cilia are microtubule-based organelles that detect mechanical and chemical stimuli. Although cilia house a number of oncogenic molecules (including Smoothened, KRAS, EGFR, and PDGFR), their precise role in cancer remains unclear. Centriole and cilia defects have been shown to be characteristic of breast cancers and to regulate cancer cell invasion. However, how ciliary signalling affects cancer survival and cell invasion is not known.

Using a number of cell lines generated in our laboratory, we will examine how centriole and cilia proteins regulate invasion in both normal and cancer cells. We will use biochemical, cell biology, molecular biology and cancer biology techniques. We will carry out western blots, invasion and proliferation assays. We will collaborate with cancer biologists, bioinformaticians and a number of laboratories in the UK and abroad.

Applicants for this project should be enthusiastic about science and willing to learn a number of new techniques.

This is a partially funded PhD. Students will get their first-year fees covered to the value of Home/EU fees, plus the benchmark fees will be funded too. Students will need to cover the remaining fees for the remaining years.

Eligibility

Candidates should have an undergraduate degree (first or upper second class) or equivalent qualification in Biosciences. A Masters qualification in a relevant area would be desirable. Experience in cell biology research, microscopy and kidney research is desirable. Applicants who have not been awarded a degree by a University in the UK will be expected to demonstrate English language skills to IELTS 7.0 (minimum 6.0 in any section).

How to apply

If you wish to apply, please e-mail the following to chmls-pgr-office@brunel.ac.uk by 30 June, 2022.

· An up-to-date CV.

· A single-page A4 single-spaced personal statement stating why you are a suitable candidate (i.e. outlining your qualifications and skills).

· One example of your academic writing (e.g. an essay, a section from an undergraduate or a Masters dissertation).

· A summary of your teaching experience or the teaching activities you feel you could support.

· Names and contact details for two academic referees.

· A copy of your highest degree certificate and transcript.

· A copy of your English language qualification, where applicable.

Short-listed applicants will be required to attend an interview. Applicants chosen for the interview will be instructed to submit a formal online application via Admissions.

For further information about how to apply, please contact the College of Health and Life Sciences Postgraduate Research Student Office on chmls-pgr-officestaff@brunel.ac.uk

Meet the Supervisor(s)


Barbara Tanos - A global nomad, Dr Barbara Tanos received her undergraduate degree from the University Buenos Aires, Argentina, and her PhD in Molecular Cancer Biology from Duke University in North Carolina (USA). As a graduate student in the laboratory of Dr Ann Marie Pendergast, Dr Tanos became interested in how signal transduction pathways regulate basic biological processes such as the trafficking of growth factor receptors throughout the cell. During her graduate studies, Dr Tanos uncovered a novel role of Abl tyrosine kinases in the regulation of the epidermal growth factor receptor (EGFR) internalization through specific phosphorylation of a tyrosine residue and through the disruption of the EGFR/Cbl interaction.  During her postdoc, Dr. Tanos began conceptualizing the idea that specific signals that drive epithelial polarity can be co- opted by cancer cells to optimize the remodeling of tumor tissue architecture, she trained with world-renowned cell biologist Dr. Enrique Rodriguez-Boulan at WCMC-NY, and wrote a review entitled “The epithelial polarity program: machineries involved and their hijacking by cancer,” and also uncovered a novel role for the scaffold protein IQGAP1 in barrier function during the establishment of epithelial polarity. After this, she began to appreciate the importance of understanding signaling from centrioles and cilia, which she hypothesized, could function as signaling hubs. Since little was known about these organelles, Barbara went to the laboratory of Dr. Bryan Tsou, an expert in the field, to learn key aspects of centrosome and cilia biology. There, Barbara identified a novel group of centriolar distal appendage proteins required for cilia formation, and uncovered the mechanism and cell cycle regulation of centriole docking to the plasma membrane. This work was published in Genes and Development, has been highly cited and it is considered to be a hallmark paper in the field. The proteins she described have now been causally linked to hereditary syndromes involving cilia defects (ciliopathies). At Brunel University, Dr Tanos’s lab focuses on understanding the mechanisms of regulation of centrioles and cilia, how they function as signalling platforms, and what the consequences of their misregulation are in disease. Using a unique mix of expertise in signal transduction, biochemistry, cancer biology and cell biology she uses this information to find and exploit therapeutic opportunities both for cancer and ciliopathies. Work from the Tanos Lab,  has been recently published in Cell Reports, describing a truly novel and fascinating story on the role of primary cilia in promoting resistance to a variety of cancer drugs: https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30749-6, and was featured in the MRC and other news websites: http://bpod.mrc.ac.uk/archive/2018/6/28, https://www.icr.ac.uk/news-archive/stunting-cell-antennae-could-make-cancer-drugs-work-again. and Dr. Tanos was interviewed on the radio, http://news.radiojackie.com/2018/06/the-institute-of-cancer-research-in.html External website: tanoslab.org