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New biomarkers and drug targets for early diagnosis and treatment of brain tumours -a 4 year Cancer Research UK funded PhD

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  • Full or part time
    Dr K Kurian
    Prof R Martin
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

The University of Bristol is offering a 4-year full time PhD funded by CRUK in research on the early detection of brain tumours with an available start date from April 2020.
The Stipend is £19000 per year with consumables of £20,000 available throughout the PhD.

The studentship is based with the University of Bristol Brain Tumour Research Group and the Cancer Research UK Integrated Cancer Epidemiology Programme For further information please see the websites below
https://www.bristol.ac.uk/integrative-epidemiology/programmes/icep/
https://www.bristol.ac.uk/translational-health-sciences/research/neurosciences/research/brain-tumour/

This CRUK PhD is part of a larger project grant including Dr Sabine Hauert, Engineering, Prof Carmen Galan, Chemistry, Dr Neciah Dorf, Fluoretiq who will develop a nanoparticle blood test with the viable biomarkers generated by this PhD project.

The project:

Brain tumours such as glioma and brain metastases from other primary sites have an overall 5-year survival rate of 20%, in part due to their late detection because their symptoms are so non-specific. At present little is known about the development of brain tumours, and there is an absence of new biomarkers for their detection and drug targets for their treatment. Early diagnosis is key for improving morbidity and mortality in these patients.
The only currently accepted treatment approaches are radiotherapy followed by standard chemotherapy. There is some speculation about a number of potential biomarkers and associated mechanisms of brain tumour development and progression that could offer new prevention and treatment strategies, but it is uncertain whether these associations are causal or reflect bias or confounding.
Mendelian randomization (MR) is a statistical methodology that uses genetic variants to test whether observational associations of risk factors, biomarkers, molecular intermediates and new drug targets with diseases and their outcomes represent causal relationships (Davey-Smith & Hemani, 2013).

Aims & Objectives

(1) To perform Mendelian randomization and to identify new biomarkers, molecular intermediates and drug targets for early diagnosis and drug targets to prevent brain tumour development and progression
(2) To validate novel biomarkers and drug targets in TCGA and other clinically relevant databases, using triangulation
(3) To liaise with the translational and nanoparticle development team to validate novel biomarkers

Methods

A search of PubMed articles will be conducted to identify previously published observational studies and meta-analyses describing an association between intermediate mechanisms, potential drug targets and brain tumour incidence. Genetic instruments for the identified biomarkers and drug targets will be prepared by extracting publicly available GWAS summary data from the largest corresponding European study (non-instrumentable risk factors will be excluded). Using two-sample Mendelian randomization, we will use these genetic instruments to appraise the causal relevance of the identified intermediates and drug targets for incidence of brain tumours. We will examine molecular intermediates in an MR framework, and correlate with other laboratory investigation of novel biomarkers we identify using MR, using targeted Next Generation Sequencing

Candidate requirements:

Applications are welcome from high performing individuals across a range of disciplines closely related to mathematics, genetics, statistics who have, or are expected to obtain, a 2.i or higher degree. Applications are particularly welcome from individuals with a relevant research Masters degree. The candidate must be available to start full time PhD studies by October 2020.

How to apply:

Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select Faculty of Health Sciences and Population Health PhD on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form.
For general enquiries linked to the online application process, please email [Email Address Removed]
Please provide a current CV, covering letter, certified copies of degree certificates and transcripts, and two academic references.

Funding Notes

The studentship is funded by the CRUK at standard CRUK rates Standard CRUK eligibility criteria apply. Only applicants from the UK or EU are eligible to apply for this programme.

References

Davey Smith G, Hemani G (2014). Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet, 23(R1), R89-R98.



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