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Decoding the role of Long Non-coding RNAs as drivers and biomarkers of cutaneous squamous cell carcinoma progression

  • Full or part time
  • Application Deadline
    Friday, April 17, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Cutaneous Squamous cell carcinoma (cSCC) is one of the commonest malignancies in the western world with incident rates increasing year on year. cSCC represents a massive health and economic burden yet despite this, there is a paucity of efficacious treatment options available for advanced disease. Chronic ultraviolet radiation exposure of the skin results in DNA damage that underpins the transformation of keratinocytes or their progenitors. This can result in the growth of cell clones in the skin followed by the development of pre-malignant Actinic Keratoses (AK), primary cSCC and ultimately potentially lethal metastatic disease.
Molecular profiling studies have revealed that complex genomes harbouring numerous rearrangements and up to thousands of mutations are present in both AK and cSCC with some of these being detectable in normal skin (1). This makes stratification of disease progression based difficult and hampers the development of targeted therapeutics. We have performed a large scale RNASeq profiling of RNA expression in tissue samples and 16 cSCC cell lines. Our analysis reveals that changes in RNA species accompanies disease progression. Notable changes are observed in long non-coding RNAs (LncRNAs) and their functional roles in determining cell behaviours make them ideal candidates of controllers of cSCC progression, potential therapeutic targets and potential biomarkers of disease progression.
Following bioinformatic ranking, we will determine the biological function of LncRNAs in cSCC using a suite of proliferation, migration and invasion assays in 2D, 3D and organotypic culture. Mechanism of action will be investigated initially using RNAseq and biomarker potential will be studied using TMAs of human tumour material.

The Cancer Research UK Beatson Institute in Glasgow is one of the world-leading centres for cancer research. The Institute provides an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies with special emphasis on imaging, metabolomics and in vivo models of cancer.

To apply, please click on the ’Visit Website’ button, which will take you to the Beatson Institute website where you should fill in the application form. Please do not email your CV.

Funding Notes

This 3-year project is funded by the British Skin Foundation and is open to UK/EU nationals only. The studentship will cover tuition fees and provide a stipend of £15,245 in year 1 (rising to £15,727 by year 3). The candidate will be enrolled at the University of Glasgow and join the PhD programme at the CRUK Beatson Institute with a proposed starting date of October 2020.

References

G. J Inman, G.J. , Wan, J. g et al., (2018). The genomic landscape of cutaneous SCC reveals drivers and a novel chronic azathioprine associated mutational signature. Nature Communications Sep 10;9(1):3667.

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