KESS2 PhD in Biosciences: A Drosophila in vivo platform for the identification of radiation sensitivity biomarkers
|Application deadline||1 October 2017|
|Start date||1 January 2018|
|Level of study||Postgraduate research|
|Award type||PhD studentship|
|Number of studentships||1|
Radiotherapy is an essential component of cancer treatment, indicated to ~50% of all cancer patients, responsible for 40% of cures, and very cost effective (5% of the cancer care costs).
However, its efficacy is limited by the toxicity of ionising radiation to the normal tissue, whose effects can be both acute (hours to weeks after treatment) and chronic (months to years). Late effects can be very serious and have a great impact in the quality of life of cancer survivors, years after treatment. With an increasing population of cancer survivors (2 million in the UK, of which probably ~100.000 are in Wales), chronic radiation injury is a mounting health care concern.
Currently, radiotherapy doses are generally defined so that less than 5% of patients will suffer serious late toxicity. Thus, the ability to stratify patients according to biomarkers of radiation sensitivity would be highly desirable, as it would allow prescribing personalised radiation doses. Likewise, insights into the nature of late toxicity could lead to co-treatments to ameliorate these side effects.
The project aims at identifying potential biomarkers for predisposition to chronic radiation injury in cancer patients receiving radiotherapy. To model late radiation injury in a genetic organism, we will use the fruit fly, Drosophila melanogaster, with assays for this purpose developed in JdN’s lab with support from the NC3Rs. The experimental plan will include quantitative genetics to identify loci potentially involved in radiation tolerance, functional genetics using the Drosophila genetic toolkit to validate candidate genes identified by the quantitative genetics approach as well as those obtained from the literature and previous work in JdN’s lab.
The work plan is divided in three phases, which will be performed sequentially or in parallel as the project develops:
- First, you will record lifespan and intestinal function traits after sub-lethal irradiation in a targeted sub-collection of the Drosophila Genetic Reference Panel (a collection of highly inbred lines that has been fully genotyped). With the phenotypic data generated and the genotype of these lines available, a quantitative genetic analysis will be performed to identify regions of the genome associated with either resistance or sensitivity to late radiation resistance. This phase will coincide with the training in fly genetics, bioinformatics and quantitative genetic analysis.
- Candidates from phase 1 will be assessed for priority based on their conservation in humans, availability of mutants, molecular function, gene expression, etc. Our partner Tenovus will be highly involved in this phase. This phase will be developed in parallel with the first as much as possible.
- The top 10-15 candidates will be functionally validated for an effect on late radiation toxicity, using available mutants as well as UAS-controlled gene-specific RNAi transgenes (expressed with a ubiquitous driver such as tubulin-Gal4 or, whenever the gene is expressed in a tissue-specific fashion, the corresponding tissue-specific Gal4 driver). One or two validated genes with a suggestive biological mechanism will be further studied, to gain insight into the cellular and molecular basis of their role in radiation toxicity using additional methods (microscopy, immunohistochemistry) to obtain additional insight into the origins of late radiation injury.
Please take note that this is a distinct funding opportunity from a related project advertised under the GW4 BioMed Doctoral Training Partnership (A Drosophila in vivo platform for the study of chronic radiation injury); each opportunity corresponds to related, but non-overlapping projects, and have different eligibility requirements.
|Tuition fee support||Full UK/EU tuition fees|
|The KESS2 scholarship will provide a stipend, plus c. £3K a year available to support project-related expenses. Fees will be met by the University.|
|Maintenance stipend||Starting stipends of £14,198 per year for PhD studentships and £11,358 a year for MRes/MPhil studentships (exact figures subject to confirmation of start date and an income assessment).|
|Residency||UK Research Council eligibility conditions apply|
Applicants for research PhDs at Cardiff University are expected to have one or both of the following:
- have a home or work address in the West Wales and the Valleys region at the time of their application for KESS funding and their enrolment for the course of study
- have a legal right to live and work in the UK for the duration of the KESS2 support, and the right to take up paid work in the WWV region on completion of the scholarship
- be classified as a ‘home’ or ‘EU’ student.
The Convergence area covers West Wales and the Valleys, and is made up of the following 15 local authorities:
- Isle of Anglesey
- Neath Port Talbot
- Rhondda Cynon Taf
- Merthyr Tydfil
- Blaenau Gwent
Applicants must also be prepared to provide proof of identity and income as part of the stipend assessment process. Further details are available from the KESS2 Office.
Consideration is automatic upon application for admission to the Doctor of Philosophy in Biosciences with a January 2018 start date.
Applicants should include a personal statement, research proposal, curriculum vitae, and covering letter. It would be desirable that applicants refer to their specific motivation to apply for this project (aims as well as model organism) in their personal statement.
In the funding section of your application, please select 'I will be applying for a scholarship/grant' and specify that you are applying for advertised funding from KESS2. In the research proposal section, include the project description contained here.
Applicants are also strongly encouraged to contact Dr Joaquin de Navascues, sending a CV and cover letter, as well as any specific enquiries about the project.
We reserve the right to close applications early should sufficient applications be received.
Funding opportunity provided by: