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Characterisation of the RNA cargo of extracellular vesicles in Tuberous Sclerosis Complex


   Cardiff School of Medicine

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  Dr E Dunlop, Dr Hywel Williams, Dr Jason Webber  No more applications being accepted  Self-Funded PhD Students Only

About the Project

Summary

Tuberous Sclerosis Complex (TSC) is a genetic syndrome where patients are pre-disposed to develop tumours in multiple organs. This project will use a range of in vitro and in silico techniques to explore the role of extracellular vesicles (EVs) in TSC. The knowledge gained from this project will improve our understanding of mechanisms regulating TSC tumour growth and help us identify potential biomarkers for monitoring disease progression.

Background

Regulators of tumour growth and progression do not come solely from the tumour cells, but there are additional influences from the environment surrounding the tumour. Communication between the tumour cells and their environment can determine whether the tumour grows, invades surrounding tissue, is eradicated or is resistant to therapy. One important means of communication is through extracellular vesicles (EVs). These are membrane bound packages containing proteins and nucleic acids. These EVs are released by all cells, but there is evidence that vesicles released from tumour cells can transfer tumour-promoting molecules to neighbouring cells, influencing tumour growth.

Our work studies tumour growth in the rare genetic condition, Tuberous Sclerosis Complex (TSC). Patients with TSC develop benign cysts and tumours within multiple organs. The condition is caused by mutation of either the TSC1 or TSC2 genes, leading to activation of the mTORC1 signalling pathway, a key regulator of cell growth. To date, research and clinical therapies for TSC have focussed on the disease-causing TSC cells, but communication with the adjacent normal cells could also be contributing to disease progression. We have been exploring the number and content of EVs released by TSC cells in order to determine whether the tumour growth promoted by EVs in cancer is mirrored by the action of EVs in TSC.

Project Plan

We have found a wide variety of biological cargo is packaged within EVs from TSC cells. We hypothesise that molecules within this cargo could act as biomarkers of TSC or could provide new targets for treatment of the condition. This PhD project will build on our existing RNA sequencing data to explore the RNA cargo in TSC EVs. The current treatment for TSC is an mTOR inhibitor called rapamycin, so this project will also investigate the impact of rapamycin on EV cargo and function. In addition to the bioinformatic work, cell culture analysis will determine how EV cargo alters the behaviour of neighbouring, non-disease cells. The overall aim is to develop a better knowledge of TSC-derived EV function in order to reveal novel mechanisms behind TSC pathology and potential new biomarkers of disease.

Environment

The Division of Cancer and Genetics at Cardiff University has a strong track record of successful PhD projects. The supervisory team bring expertise from the fields of TSC, EV biology and transcriptomics, so the student will be supported through all aspects of the project. The student will have opportunities to present their work at local, national and international conferences and will join an active post-graduate community within the Division.

Application Process

We are seeking enthusiastic and motivated students with an interest in Cancer or genomic research. Applicants should possess a minimum of an upper second-class Honours degree, master's degree, or equivalent in a relevant subject.

Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

The total duration of this PhD programme is 3.5 years. Following discussion with proposed supervisors and to be considered you must submit a formal application via Cardiff University’s online application service. Medicine - Study - Cardiff University

There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (i.e. April 2022). This will take you to the application portal.

In the ‘Research Proposal’ section of the application enter the name of the project you are applying to.

Candidates must submit the following information:

  • Supporting statement 
  • CV 
  • Qualification certificates 
  • Proof of Funding i.e. a letter of intent from your sponsor or confirmation of self-funded status.
  • References x 2 
  • Proof of English language (if applicable)

Closing date for applicants is the 31st March 2022.


Funding Notes

This is a Self-Funded/Sponsored PhD opportunity.
FUNDING REQUIRED:
Full UK/EU or International Tuition Fees
UK Living Expenses
Bench Fees (where applicable)
Open to all students of any nationality without restrictions (UK/EU and International)
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