Immunotherapy has transformed the treatment landscape of non-small cell lung cancer (NSCLC), offering life-changing survival benefits to a minority of patients with stage III/IV disease. Progress with immune checkpoint inhibitors (ICIs) is now being limited by the lack of a reliable predictive biomarker that can inform i) which patients are most likely to benefit from treatment, and ii) which patients should avoid treatment given a projected lack of efficacy and/or toxicity risk. A key bottleneck in identification of a novel predictive biomarker for ICIs is the deficit of reliable preclinical lung cancer models that can simulate immunotherapy response: cell culture is usually limited to cancer cells alone, xenografts are immune-deficient and, in contrast to the human disease, genetically-engineered mouse models (GEMMs) of lung cancer are characteristically immune ‘cold’.
This project will focus on answering this important unmet need by exploiting the supervisors’ combined expertise in RAS mutations and signalling (Lindsay, Malliri), and using whole genome sequencing to detail aetiological variation and its impact on KRAS-mutant NSCLC (Wedge). It will follow the principle of reverse translation, using bioinformatic work from resected lung cancers (Genomics England 100,000 genome project) to inform generation of novel KRAS-mutant mouse models that more closely recapitulate the human cancer using advanced carcinogen exposure protocols and molecular biology techniques. Using existing KRAS-mutant lung cancer GEMMs available at the University of Manchester and CRUK Manchester Institute, the student will use data from whole genome sequencing to inform a more sophisticated approach to mouse modelling that will fulfil the combined aims of i) offering a new (and rare) preclinical model that is susceptible to immunotherapy and can leverage predictive biomarker identification, and ii) offering a more faithful recapitulation of KRAS-mutant lung cancer than existing lab-based models.
Entry Requirements
Candidates must be post-registration clinicians and ideally have a specialist post in a related subject. It is generally expected that CRTFs will return to a training programme in the UK upon completion of their research degree.
How to Apply
To be considered for this project you MUST submit a formal online application form. Details of how to apply are available here (https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mcrc-training-scheme/apply/). For Visa requirements, international candidates must select the full-time study option.
General enquiries can be directed to [Email Address Removed].
Interviews: Week commencing 10 January 2022
Commencement: April 2022, October 2022 or January 2023
Equality, Diversity and Inclusion
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/
Continue with Facebook
