About the Project
This project will identify ncRNA species (circRNAs, miRNAs, lncRNAs, tRFs) that are dysregulated in matched HCC and background non-malignant tissue from the same patient. Once characterised we will identify essential ncRNA:ncRNA interactions which dysregulate mRNA expression in HCC. Finally, the role of these target mRNAs controlled by dysregulated ncRNA networks will be examined in HCC development and progression.
This project is highly novel and very timely as molecular crosstalk between ncRNA species is an emerging regulatory layer of gene expression. ncRNA networks pervade and define the correct functioning of canonical protein-coding pathways involved in many cellular processes, consequently dysregulation of these networks is implicated in a wide range of human diseases, particularly cancers. Importantly, development of applied NGS-based technologies now allows the identification of dysregulated ncRNA species in cancerous versus non-malignant tissue. These dysregulated ncRNAs in HCC may provide potential prognostic or diagnostic biomarkers and may have future potential applications in RNA-targeting therapeutics, such as ASO and RNAi-based approaches.
This project is highly interdisciplinary drawing on the expertise of supervisors in RNA biology, cancer research and bioinformatics. The project will utilise a range of cutting-edge techniques including: NGS-based approaches (CircSeq, Small RNA-Seq and RNA-seq) established in the primary supervisor’s laboratory. Once identified the roles of these ncRNA network-regulated mRNAs will be examined in HCC proliferation and growth assays using depletion/overexpression studies. Finally, the effect of reversing the dysregulation of ncRNAs will be examined on HCC proliferation and growth, using virus-based delivery of LNA-oligonucleotides or ncRNA mimics.
More information of supervisors research expertise can be found at :
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
Studentships commence: 1st October 2021
Anastasiadou, E., Jacob, L. & Slack, F. Non-coding RNA networks in cancer. Nat Rev Cancer 18, 5–18 (2018).
Yang, J.D., Hainaut, P., Gores, G.J. et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16, 589–604 (2019)
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