Development of molecular methods for clinical therapeutic drug monitoring

An exciting opportunity to apply for a fully funded PhD position in the College of Health, Science and Society, UWE Bristol.

Ref: 2324-OCT-HSS09

The expected start date of these studentships is 1 October 2023.

The closing date for applications is 9 June 2022.

This is an exciting opportunity to study for a fully funded PhD in Molecular Haematology within the thriving Centre for Research in Biosciences at the University of the West of England. Myelodysplasia (MDS) is a disease that negatively affects the bone marrow, resulting in production of immature, non-functional blood cells. This can be caused by epigenetic mutations in genes such as tet2, resulting in DNA hypermethylation. MDS can also progress to acute myeloid leukaemia (AML), where outcomes are poor, particularly in older individuals.

Hypomethylating agents (HMAs) such as azacytidine (AZA) are used to treat a range of malignancies by reducing methylation of DNA. In MDS, they are frequently used to prevent disease progression and subsequent transformation to AML, however they are currently administered without prior assessment of likely efficacy/resistance. AZA is expensive, costing ~£37K-£47K per quality-adjusted life-year gained, with only ~40% of patients showing long-term benefit, and relapse frequent even in early responders. Furthermore, recent studies have found no clear biomarker for predicting outcome using conventional mutational or cytogenetic aberration analysis. Therefore, this project seeks to develop a novel method of analysis to determine patient suitability for sustained AZA therapy, and longer-term monitoring of efficacy. 

This project builds on our pilot in vitro work using methyl-specific enzyme digestion of DNA coupled with high-resolution melt analysis (HRM), and quantitative PCR (qPCR), in relevant immortalised cell lines and patient blasts. The optimised method would be used in therapeutic drug monitoring of HMA drugs such as AZA, allowing clinicians to tailor patient treatment, improving clinical outcomes, and reducing treatment costs via early identification of resistant patients.

For an informal discussion about the studentship, please email Elizabeth Anderson at elizabeth3.anderson@uwe.ac.uk.

The studentship is available from 1 October 2023 for a period of three and half years, subject to satisfactory progress and includes a tax exempt stipend, which will be £18,622 per annum (2023/24).

In addition, full-time tuition fees will be covered for up to three years.

Applicants must have at least a 2:1 or equivalent degree in Biomedical Science, Molecular or Biological Science or a related discipline and ideally will have or be working towards a postgraduate, research-based qualification (or equivalent experience).

Knowledge of relevant molecular and cell culture techniques, including primary cell culture would be an advantage.

A recognised English language qualification is required.

Please submit your application online. When prompted use the reference number 2324-OCT-HSS09.

Supporting documentation: You will need to upload your covering letter, all your degree certificates and transcripts and your proof of English language proficiency as attachments to your application, so please have these available when you complete the application form.

References: You will need to provide details of two referees as part of your application. At least one referee must be an academic referee from the institution that conferred your highest degree. Your referee will be asked for a reference at the time you submit your application, so please ensure that your nominated referees are willing and able to provide references within 14 days of your application being submitted.

The closing date for applications is 9 June 2023.

It is expected that interviews will take place on weeks commencing 10 July 2023. If you have not heard from us by the end of July 2023, we thank you for your application but on this occasion you have not been successful.