Identification and functional importance of RNA and lipid biomarkers in colorectal cancer metastases to liver

Identification and functional importance of RNA and lipid biomarkers in colorectal cancer metastases to liver

Department: College of Health and Life Sciences

Contract Type: Fixed Term

Basis: Full Time

Closing Date: 30th June 2023 [23:59 GMT]

Supervisory Team: Dr Theo Kantidakis (Main Supervisor, Aston University Medical School)

Dr Akinfemi Akingboye (Associate supervisor, Dudley Group NHS Foundation Trust)

Dr Irundika Dias (Associate supervisor, Aston University Medical School)

Keywords: Cancer, metastasis, colon, liver, TCGA, RNA-seq, qPCR, molecular biology, cell biology, biochemistry

Applications are invited for a three-year Postgraduate studentship, supported by the College of Health and Life Sciences, at Aston University.

The position is available to start in October 2023

Financial Support

This studentship includes a fee bursary to cover the Home fees rate, plus a maintenance allowance of £18,622 in 2023/4.

Overseas Applicants

Overseas applicants may apply for this studentship but will need to pay the difference between the ‘Home’ and the ‘Overseas’ tuition fees. Currently the difference between ‘Home’ and the ‘Overseas’ tuition fees is £14,338 in 2023/4. As part of the application, you will be required to confirm that you have applied for or secured this additional funding. The maintenance allowance cannot be used to cover the tuition fees.

Background to the Project

Colorectal cancer (CRC) is the 3rd most common cancer in the UK accounting for 11.4% of all new cases1. Despite improvements in detection and treatment, CRC ranks second in terms of mortality2. To improve CRC patient survival, it is essential to increase its early detection and metastases. Considering that about 20% of CRC patients present synchronous metastases at the time of diagnosis, most of which are found in the liver3, a valid strategy is to identify novel biomarkers that have the potential to distinguish these metastases at the earliest possible time. This project aims to discover, verify and functionally understand molecular signatures common in metastatic CRC and early liver metastases, that might also manifest in patients’ blood/serum

The PhD candidate will analyse existing large CRC and liver cancer datasets (TCGA, ICGC, Genbank) to identify genes that are differentially expressed, mutated or methylated in metastatic tumours, when compared to non-metastatic or healthy tissue. Protein-coding (mRNA) genes, as well as long and short ncRNAs, including tRNAs and miRNAs, will be examined. Once promising biomarkers have been defined, their expression will be verified in CRC patients’ samples, either by qPCR or highly sensitive mass-spectroscopy methods to identify lipid metabolites and oxylipids. The PhD candidate will then functionally characterise them in commercial colon and liver, cancer and non-cancer cell lines. This will include knocking down their expression and testing the survival and metastatic potential after X-ray irradiation or chemotherapeutic agent treatment.

We will use a variety of approaches to answer the experimental questions, including cell biology, molecular biology, biochemistry and computational methods that we have previously established4–10.

References

1 Sung, H. et al. CA Cancer J Clin 71, 209–249 (2021)

2 Cancer survival in England - Office for National Statistics. (2019)

3 Reboux, N. et al. JAMA Netw. Open 5, e2236666 (2022)

4 Dias, I. H. K. et al. J Alzheimers Dis 87, 1527–1536 (2022)

5 Rossin, D. et al. Free Radic. Biol. Med. 136, 35–44 (2019)

6 Saponaro, M. et al. Cell 157, 1037–49 (2014)

7 Kantidakis, T. et al. Genes Dev. 30, 408–420 (2016)

8 Williamson, L. et al. Cell 168, 843-855 e13 (2017)

9 Sangha, A. K. et al. Curr Issues Mol Biol 44, 3001–3017 (2022)

10 Kanagaraj, R. et al. Proc Natl Acad Sci U S A 119, e2114314119 (2022)

Person Specification

The successful applicant should have been awarded, or expect to achieve, a Masters degree in a relevant subject with a 60% or higher weighted average, and/or a First or Upper Second Class Honours degree (or an equivalent qualification from an overseas institution) in a relevant subject.

Contact information

Please contact Dr Theo Kantidakis (t.kantidakis@aston.ac.uk)for questions about the project.

Submitting an application

As part of the application, you will need to supply:

• A copy of your current CV
• Copies of your academic qualifications for your Bachelor degree, and Masters degree (if studied); this should include both certificates and transcripts, and must be translated in to English
• A research proposal statement*
• A personal statement
• Two academic references
• Proof of your English Language proficiency

• The application must be accompanied by a “research proposal” statement. An original proposal is not required as the initial scope of the project has been defined, candidates should take this opportunity to detail how their knowledge and experience will benefit the project and should also be accompanied by a brief review of relevant research literature.

Details of how to submit your application, and the necessary supporting documents can be found here.

Please select “Research Health Sciences” from the application form options.

Please include the supervisor’s name, project title and project reference in your Personal Statement.

If you require further information about the application process, please contact the Postgraduate Admissions team at pgr_admisssions@aston.ac.uk