This 4-year PhD studentship will be based initially at the Cancer Research UK Manchester Institute, Alderley Park, Alderley Edge, Cheshire. The rebuilding of our world class research facilities is well underway, and we anticipate returning to our original site in Withington, Manchester, UK in 2023 next to the Christie NHS Foundation Trust
Small Cell Lung Cancer (SCLC) is characterised by rapid growth, prevalent circulating tumour cells (CTCs), and early metastasis. The cancer cells are initially highly chemosensitive but invariably relapse with chemoresistance for reasons that are not understood. We pioneered patient CTC derived explant mouse models (CDX) of SCLC, generated from only 10ml of a patient's blood, to generate ‘paired’ pre- and post-chemotherapy preclinical models that facilitate investigations into the biology of acquired chemoresistance.
In addition to identification of drug resistance mechanisms we aim to discover new targets for mechanism-based therapies that can be tested second line after failure of standard treatment. We have over 50 CDX models, including seven pre- and post-chemotherapy CDX pairs from the same patient that will form the experimental basis of this proposal. The project seeks to characterise SCLC evolution through therapy, to explore mechanisms of acquired chemo-resistance and discover novel therapy targets. We have already identified genes of interest that are significantly up- or down-regulated between each of the baseline and progression paired models.
You will firstly conduct a proteomic analysis of the paired CDX models and integrate their data with the existing RNAseq profiles, building proteo-genomic maps of the pre- and post-chemotherapy CDX models. You will subsequently interrogate functional consequences of up- or down-regulation of selected pathways based on differential gene and protein expression using a range of ex vivo cell fate experiments and in vivo studies.
Registration and graduation will be affiliated to the University of Manchester.
Commencement dates are flexible with entry point either April or September 2022.
Successful applicants will receive a non-taxable annual stipend (living allowance) of £19,000 per annum and funding to cover University tuition & bench fees for the 4 years.
Our PhD Studentships are open to applicants from all nationalities.
You can find further information, entry criteria and details on how to apply online
Closing date: Monday 31 January 2022 @ 1700 hrs GMT
Zoom virtual interview date: Monday 14 February 2022
Cancer Research UK Manchester Institute is a Research Institute within The University of Manchester and is core funded by Cancer Research UK
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