Metabolism of amino acids as a therapeutic target and predictor of leukaemia patient outcome

An opportunity to apply for a funded full-time PhD in the College of Health, Science and Society, UWE Bristol. The studentship will be funded by UWE Bristol.

Ref: 2223-APR-CHSS04

The expected start date of this studentship is Saturday 1 April 2023.

The closing date for applications is Sunday 12 February 2023.

Leukaemia is responsible for the death of over 350,000 people annually worldwide, with over 75% of these deaths occurring in individuals over 65 years of age (Cancer Research UK). Intensive chemotherapeutic intervention is initiated immediately, however only 5% of the elderly population can be cured (Eleni et al., 2010). In addition, the poor fitness of many elderly individuals leads to quality-of-life issues when considering treatment (Klepin et al., 2014). It is therefore imperative that new treatment options are produced for this deadly disease.

Our previous work in glioblastomas demonstrated that there is an increased expression of amino acid metabolising enzymes in this cancer. Furthermore, one of these enzymes correlated with a more aggressive phenotype, and poorer outcome for the patient (Conway et al., 2016) establishing aberrant amino acid metabolism as a driver of cancer progression. Furthermore, our work in leukaemic cell models have demonstrated that:

• leukaemic metabolic profile correlates with chemotherapy resistance in culture, and
• each cell line has a unique nutritional requirement.

This strongly indicates that our previous findings in glioblastoma will be repeated in leukaemia samples.

The techniques that will be most heavily used in this PhD include wet transfer Western blotting, tissue culture, viability assays, and use of the Seahorse XFe24 Metabolic Analyser. Experience in at least some of these techniques would be ideal – however you will certainly not be expected to know all of them.

This project has great potential to further our understanding of leukaemia and amino acid metabolism in cancers, leading to novel therapeutic opportunities. The metabolic sensitivity of leukemic cells to amino acid deprivation will lead to a targeted therapy in leukaemia through dietary restrictions or enzymatic infusion, acting as an adjunct to chemotherapy. Metabolic changes are a key mechanism driving cancer progression however, they are currently underexploited.

References

• Cancer Research UK – accessed January 2021.

For an informal discussion about the studentship, please contact Jonathon Hull at jonathon2.hull@uwe.ac.uk.

The studentship is available from Saturday 1 April 2023 for a period of three and half years, subject to satisfactory progress and includes a tax exempt stipend, which is currently £17,668 per annum.

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

Applicants must have BSc in an applied science (e.g. biomedical science) and ideally will have an MRes of MSc.

Please submit your application online. When prompted use the reference number 2223-APR-CHSS04.

Supporting documentation: You will need to upload your research proposal, 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 Sunday 12 February 2023.

It is expected that interviews will take place on weeks commencing Monday 6 March 2023. If you have not heard from us by this date, we thank you for your application but on this occasion you have not been successful.