Development of novel pyrazolyl-urea compounds as novel anticancer drugs

An opportunity to apply for a funded full-time PhD in the Faculty of Health and Applied Sciences at UWE Bristol. 

The expected start date of this studentship is 1 January 2023.

The closing date for applications is 19 August 2022.

Ref: 2223-JAN-HAS02 

Please note: out of the eight projects being advertised for the Dean’s Studentship, the faculty will fund four. The projects for funding will be selected based on the merit of applicants following the process outlined below.

There will be a two stage interview process. Supervisory teams of each project will shortlist the best candidates for an initial interview with the supervisory team. Following this first interview, two candidates will be selected; a first-choice candidate and a reserve candidate. The first-choice candidate (or the reserve, if the first-choice candidate is unavailable) will then be interviewed by a Faculty Panel (the second interview). The Faculty Panel will be chaired by Pro-Vice Chancellor and Executive Dean and will consist of senior Faculty staff. The Faculty level interview will take place on the 31 October 2022.

Unsuccessful candidates will have the opportunity for self-funded places.

Cancer is one of the most critical health challenges world-wide, and some cancers, such as pancreatic cancer, remain particularly challenging with very poor five-year survival rates. As a result, there is a pressing need to continue developing new anticancer drugs that can both extend life and improve the quality of life of patients.

One class of compounds that has recently attracted significant interest are the pyrazolyl-urea compounds. These are derivatives of pyrazoles, heterocycles characterised by a five-membered ring of three carbons and two adjacent nitrogens. They are already established as widely used drugs, e.g. celecoxib, a non-steroidal anti-inflammatory drug (NSAID). They are now being explored as potential anticancer drugs.

The aim of this research project is to perform a detailed in vitro evaluation of the anticancer properties of three novel pyrazolyl-urea compounds. The compounds, developed by our collaborator Dr Chiara Brullo at the University of Genova, are the pyrazolyl-urea compounds GeGe-3, STIRUR-41 and TBB47A. The project will involve extensive cell biology assays on a range of cancer cell lines using standard in vitro and organoid tumour models. The project will also involve examining gene expression changes, mainly through RNASeq analysis of treated cancer cells.

The long-term aim, following this PhD, is to proceed to more detailed pre-clinical research on the anticancer effectiveness of these compounds on in vivo models. Follow-up preclinical research will then provide the basis for future clinical trials.

For an informal discussion about the studentship, please email Professor Michael Ladomery at michael.ladomery@uwe.ac.uk and Dr Alexander Greenhough at alexander.greenhough@uwe.ac.uk.

This is a Dean’s PhD studentship and is funded for a period of three years, subject to satisfactory progress and includes a tax-exempt stipend, which is currently £16,602 per annum.

In addition, full-time tuition fees will be covered for up to three years. The studentship will also fully cover the research costs (consumables budget).

Applicants must have a First-Class or Upper Second-Class BSc in a compatible subject area with a solid grounding in molecular biology.

Applicants ideally will also have obtained an MSc or MRes in a compatible subject, and/or postgraduate laboratory experience working as a research assistant.

If applying from overseas, a recognised English language qualification is also required.

Please submit your application online. When prompted use the reference number 2223-JAN-HAS02. 

In the application form, the section that asks you to upload a proposal, please upload a covering letter. 

Supporting documentation: you will need to upload your degree certificates and transcripts and if required, 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 may be asked for a reference from 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 19 August 2022.

Please note that the following selection process applies.

Interviews by the prospective supervisory team will take place in the week commencing 12 September 2022. If you have not heard from us by that date, we thank you for your application but on this occasion you have not been successful.

Following the initial interview, two candidates will be selected; a first-choice candidate and a reserve candidate. The first-choice candidate (or the reserve, if the first-choice candidate is unavailable) will then undertake a second interview by a senior faculty panel on the 31 October 2022. The PhD will be awarded following a successful second interview.