Cancer Research UK Clinical Research Fellowships
Interviews: 11th December 2015
Our Cancer Research UK clinical research fellowship provides up to 3 years' support for clinically qualified professionals to undertake research training within Barts Cancer Institute.
This training programme, part of a multi million pound award from Cancer Research UK, aims to develop a cohort of medically qualified scientists equipped both intellectually and technically to conduct the highest quality research on cancer.
The scheme is designed to accommodate the dual clinical-research training career path by allowing fellows to spend up to 20 per cent of their time on NHS sessions.
Fellows will be appointed as a Clinical Research Fellow with the Institute and will be required to register for a PhD, based on research undertaken during the fellowship.
We are now inviting applications for the following research projects:
Click on the links below for FAQs
|Can I apply?||What is the shortlisting process?|
|How do I apply?||When would I start the fellowship?|
|What funding will I receive?||Who should I speak to for more information?|
Diagnostic cytogenetics provides a universally accepted approach to stratify patients with acute myeloid leukaemia (AML) into good, intermediate and poor risk groups based on 4 year overall survival (OS) of 70%, 40% and 20% respectively. The number of patients with poor risk cytogenetics increases with age, with the incidence rising to >30% in patients over the age of 65.
Poor risk refers to the coexistence of multiple clonal cytogenetic abnormalities, often referred to as complex karyotypes. However within this group, autosomal monosomies provide a better indicator of poor prognosis than complex karyotype. Altogether these patients represent an area of unmet clinical need, where there has been no progress in elucidating the pathological role of this lesion, and knowledge of the precise gene(s) or pathway(s) responsible for dismal response to conventional therapies in this patient group.
The student will set out to create and characterise a model of monosomy 7, using a novel, CRISPR-directed approach to induce missegregation of chromosome 7 during mitosis as a means of defining monosomy 7-mediated chemotherapy resistance pathways in AML.
High grade serous ovarian cancer (HGSOC) is the most common ovarian cancer subtype. It is initially very responsive to chemotherapy but more than 70% of patients develop chemo-resistance and the disease becomes incurable. As with most cancers, circumventing chemo-resistance in HGSOC is a major unmet clinical need.
Recognising cancer as an evolutionary process offers a new opportunity to tackle this clinical problem. When cancer cells acquire new mutations that enable them to become resistant to a chemotherapy drug, they inevitably incur some “cost”. For example: drug efflux pump amplification might come at the cost of increased metabolic demand. In theory, these costs could be exploited to prevent outgrowth of the resistant clone.
The mechanism by which HGSOC cells become chemo-resistant is largely unknown, and the cost of resistance has not been quantified. This project will use a large and unique panel of chemo-resistant HGSOC cells as well as sequential biopsies and circulating tumour cells isolated from women with HGSOC. Using a combined biological and mathematical approach, we will define genetic mechanisms of chemotherapy resistance, understand how resistance evolves and the costs incurred. This will enable us to mathematically derive new treatment regimes that exploit the evolutionary trade-offs inherent in chemo-resistance and to develop therapeutic strategies predicted to forestall the evolution of resistance in HGSOC.
Fibroblast growth factor (FGF) signalling is a potent driving force in many different cancers. A variety of mechanisms underlie its effects but, in many cancers, FGFRs are oncogenic drivers. Thus the FGFR pathway represents an excellent therapeutic target, and currently is being investigated in clinical trials in a variety of cancer types.
A critical problem with targeted therapies is the development of drug resistance. We have identified a novel mechanism by which FGFR-addicted endometrial cancer cells develop resistance to FGFR inhibition, and have shown this mechanism to hold true for other receptor tyrosine kinases (RTKs). The aim of this project is to build on this understanding, both in terms of dissecting (and reversing) the pathway by which resistance occurs, and by screening for ways in which the mechanism underpinning the acquisition of resistance may make resistant cells more sensitive to synthetically lethal therapeutic approaches.
Cell based findings will be complemented by small molecule / RNAi treatment of xenograft models, to determine whether resistance to RTKs can be circumvented in vivo. Alongside this, the extent to which the resistance mechanism occurs in the clinic, together with its implications for disease prognosis will be interrogated through clinical collaborations.
Targeting recruitment, polarisation and effector functions of TAMs may improve tumour responses to chemotherapy as well as independent anti-cancer activity.
This project will investigate the effects of chemotherapy on TAM activity, location and density in the tumour microenvironment of high-grade serous ovarian cancer, including pre-clinical studies on the therapeutic potential of macrophage inhibitors in this disease and in combination with chemotherapy.
The project will use a unique set of matched patient samples taken pre and post neoadjuvant chemotherapy, new more relevant mouse models and a range of cell and molecular biology techniques. Data will be intergrated using novel bioinformatics methods.
Results will ideally be:
- a detailed description of TAM populations in patient biopsies and mouse models of HGSOC
- an understanding of the influence of chemotherapy on TAMs and
- the potential of macrophage-targeted treatments alone and in combination with other therapies in patients with advanced ovarian cancer.
Frequently Asked Questions
- A medical degree from a recognised institution.
- You should be at specialty registrar (StR) grade or below.
- Have full GMC registration.
Overseas applicant additional requirements:
- Proof of English language if you have not studied or worked in a majority English speaking country.
- Please note that the fellowship will only cover the Home/EU fee rate.
You will receive a salary commensurate with your current experience. This will be paid on the Clinical Academic scale + London weighting.
- Tuition Fees
Your fellowship will cover the tuition fees for your PhD registration up to the Home/EU rate.
This fellowship includes £15k of lab consumables.
You will be eligible to apply for travel funding from the Institute or from CRUK.
Please complete the application form and email this, together with all the supporting documents, to the BCI Teaching Centre.
- Application form
- Transcript of your degree results
- 2 references [BCI Reference request form]
- Supporting statement
- Proof of eligibility to work in the UK (copy of passport)
- Proof of English proficiency (if applicable)
Please ensure that you provide all documents required by the specified deadline. We regret we are unable to consider incomplete applications.
Please contact the supervisors directly if you wish to discuss the project.
For general enquiries about the fellowships please contact the BCI Teaching Centre.
If successful, you are expected to take up your appointment in September 2016.