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The nuclear YAP/TAZ interactome in normal versus neoplastic human epidermal cells


Project Description

Cutaneous squamous cell carcinoma (cSCC) originates from the epidermal keratinocyte. It is the second most common skin cancer in the UK and world-wide. Although the overall metastatic rate is low (2–3%), the mortality rate of distant metastatic cSCC is high (70–89%), and current treatment options are ineffective. The transcriptional regulators YAP and TAZ have emerged as important drivers of tumour initiation, progression and metastasis in cSCC and other cancers. Understanding the nuclear functions of YAP/TAZ thus offers a promising direction to design new modalities for therapeutic intervention in cSCC and other cancers.

The mechanisms by which nuclear YAP/TAZ select their downstream transcriptional programmes and transcriptional partners represent a largely unexplored but promising area to design new anti-cancer therapeutic interventions. Since all upstream signalling inputs ultimately impact on YAP/TAZ nuclear availability and transcriptional responses, designing compounds able to interfere with YAP/TAZ activities at the nuclear level may represent a ‘universal’ anti-YAP/TAZ approach.

The aim of this project is to identify and characterise the different transcriptional binding partners that enable YAP/TAZ to execute their various downstream transcriptional programmes to promote cSCC progression. You will perform state-of-the-art chromosome immunoprecipitation, RNA sequencing- and rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) experiments to establish the genomic map of YAP/TAZ recruitment to the chromatin and to obtain the first global picture of the nuclear interaction partners of YAP/TAZ in normal human keratinocytes versus cSCC cells. Furthermore, you will apply standard cell- and molecular biology techniques such as qPCR- and western blotting analysis and RNA interference to understand the physiological functions of newly identified nuclear YAP/TAZ-interacting proteins.

The project will benefit from collaborations with dermatologists, chromatin biologists, proteomics experts, computational biologist and scientists at the University of Bath, University of Cambridge, King’s College London and the Francis Crick Institute.

If you are motivated and passionate about stem cell- and cancer research and interested in a broad range of methods and want to work on an interesting and medically relevant topic, you should apply. Previous laboratory experience including an undergraduate placement or a postgraduate master’s degree in Molecular Biology or Biochemistry is essential. The applicant must meet the standard University of Bath English language requirements and is expected to hold a relevant degree.

For more information contact Dr Gernot Walko at

The University of Bath and our Department are committed to equality of opportunity. We particularly encourage applications from under-represented groups, including women.

How to apply:

Formal applications should be made via the University of Bath’s online application form:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP01&code2=0013

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section.

More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/

Anticipated start date: 30 September 2019.

Funding Notes

Candidates may be considered for a University Research Studentship which will cover UK/EU tuition fees, a training support fee of £1,000 per annum and a tax-free maintenance allowance at the UKRI Doctoral Stipend rate (£14,777 in 2018-19) for a period of up to 3.5 years.

References

Walko, G. et al. A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells. Nature communications 8, 14744 (2017).

Zanconato, F., Cordenonsi, M. & Piccolo, S. YAP/TAZ at the Roots of Cancer. Cancer Cell 29, 783-803 (2016).

Watt, F.M. Mammalian skin cell biology: at the interface between laboratory and clinic. Science 346, 937-940 (2014).

Ratushny, V. et al. From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma. J. Clin. Invest. 122, 464–472 (2012).

How good is research at University of Bath in Biological Sciences?

FTE Category A staff submitted: 24.50

Research output data provided by the Research Excellence Framework (REF)

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