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(MCRC Clinical) Liquid biopsies to support management of Ewing sarcomas


Faculty of Biology, Medicine and Health

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Prof C Dive , Dr M McCabe , Dr D Rothwell No more applications being accepted

About the Project

Ewing sarcoma (ES) is a poor prognosis primary bone and soft tissue cancer of children and young adults driven by oncogenic gene fusions including EWSR1/FLI1 and EWSR1/ERG. Small pilot studies have demonstrated that circulating tumour nucleic acids (ctDNA and ctRNA) can be detected in patient plasma at diagnosis. ctDNA correlates with tumour volume, falls with treatment and increases in abundance at recurrence. ctRNA is less well studied (reported in only 4 patients to date) but has theoretical advantages over ctDNA as a circulating biomarker, due to less inter-patient variability and greater abundance per tumour cell. This project, which is a collaboration between the CRUK Manchester Institute, University of Manchester and ThermoFisher, will explore circulating tumour DNA (ctDNA) and RNA (ctRNA) as biomarkers of disease response and progression in ES.

The project is based in the Nucleic Acids Biomarkers Team of the CRUK Manchester Institute Cancer Biomarker Centre. The team has internationally established expertise in the development and validation of nucleic acid based liquid biopsy assays. The project involves (i) Development of an Illumina NGS pulldown assay to detect ES fusions in ctRNA and in ctDNA; (ii) Optimisation of a commercial ThermoFisher assay to detect ES fusions in ctRNA; (iii) Direct comparison of the 2 methods and 2 analytes (ctRNA and ctDNA), with optimised pre-analytic variables, and selection of the superior assay to detect ES fusions in serial clinical samples from a cohort of Manchester ES patients with standard and high risk disease to determine utility for disease monitoring; (iv) analysis of baseline ctRNA and/or ctDNA from prospectively collected samples from two international ES trials and correlation with clinical risk factors and outcome; and (v) exploration of ctRNA biology, including the process of ctRNA shedding, stability and mechanisms of transported as cargo in extracellular vesicles or free ctRNA.

Entry Requirements:
Candidates must be post-registration clinicians and ideally, have a specialist post in a related subject. It is generally expected that CRTFs would return to a training programme in the UK upon completion of their research degree.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the CRUK Manchester Centre PhD Training Scheme (MCRC) website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/

General enquiries can be directed to [Email Address Removed].

Equality, diversity and inclusion is fundamental to the success of The University of Manchester and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Interview date – 8 January 2021

Funding Notes

The clinical fellowships are usually tenable for three years, although in certain circumstances they may be four years duration. We will provide running expenses, an appropriate salary in line with the applicant’s current salary and grade, and full coverage of University UK PhD fees. The University of Manchester aims to support the most outstanding applicants from outside the UK. Due to the competitive nature of this scheme, we are only able to offer a limited number of tuition fee bursaries to be awarded to international candidates of exceptional quality.

Four year project. Entry point: April 2021 or October 2021.
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