Investigating multi-drug resistance in lung cancer using metabolomics and cell biology

As part of the Stratified Medicine Graduate Training Programme in Systems Medicine and Spectroscopic Profiling (STRATiGRAD) https://www.imperial.ac.uk/stratigrad/ we are looking to recruit a PhD student to focus on a metabolism based project in partnership with AstraZeneca.

STRATiGRAD PhD opportunities are funded in partnership with the MRC, NIHR and various industrial sources. The programme embodies a “blue-skies” approach to research with an analytical and modelling focus. The programme is led by a management team including Profs Zoltan Takats, Jules Griffin, Gary Frost and Dr. Fiona Pereira. The students will be supervised by a team of high calibre scientists including an industrial co-supervisor. Each project will have a common training core and with elements of translatable skills. The Department of MDR is exceptionally well-equipped to allow students to perform multi-Omic investigations with a view to phenotyping patients to improve precision medicine.

Applications are invited for a PhD project exploring the following theme:

Osimertinib is a 1st-line treatment for non-small cell lung cancer (NSCLC) developed by AstraZeneca to inhibit mutated epithelial growth factor receptor (EGFRm). A challenge with Osimertinib treatment is the eventual development of drug resistance in a significant number of patients. A multi-omic approach is being used to characterize a number of pathways leading to the resistant state, and this information is being translated to the clinic, where treatments bypassing the acquired drug resistance are being tested. Unfortunately, resistance to Osimertinib is highly heterogeneous, and moreover a significant proportion of relapsed patients have unknown drivers of resistance.

It is known that Osimertinib-sensitive cells suppress glycolysis and have an increased dependence on oxidative phosphorylation in the presence of drug. Conversely, resistant cells maintain their glycolytic metabolism during drug treatment, and have variable sensitivities to oxidative phopshorylation inhibitors. However, little is known about changes to the basal metabolism of EGFRm NSCLC cells as they progress to resistance beyond these global energy pathways. Furthermore, genetic alterations that drive resistance in relapsed patients (e.g. PIK3CA mutation) are known to regulate metabolic pathways. This necessitates the better understanding of the metabolic changes occurring as cancer cells gain Osimertinib resistance.

The proposed project will utilize cell biology and metabolomics to phenotypically characterize established in vitro models (both acquired and genetically defined). Understanding the dynamics of tumour metabolism that accompany the development of resistance to Osimertinib will uncover fundamental mechanisms that are common across multiple resistance mechanisms and has the potential to identify actionable targets to combat this resistance. A further goal of this work is to incorporate findings with additional omics data to develop a holistic model of Osimertinib resistance.

Applicants must be Home OR EU nationals with leave to remain in the UK, and should hold or expect to obtain a Master’s degree in a relevant scientific discipline, as well as a first or upper-second class honours science degree or equivalent. All Imperial College PhD entry requirements must be met (see http://www3.imperial.ac.uk/entryrequirements/graduate).


To apply, please send a covering letter stating your project preference, full CV and contact details of two referees, one of whom must be academic, to Dr Fiona Pereira ([Email Address Removed] ).

The deadline for applications is 04/09/20. Short-listed candidates will be informed by email and it is expected that interviews will take place the week commencing 14/09/20.