Post-Doctoral Research Associate

Centre for Cutaneous Research

Development of 3-dimensional in vitro systems for the assessment of therapeutic responses of cancer stem cells.

A postdoctoral research associate position is available at the Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London. The research will focus on the development and testing of 3-dimensional models of head and neck cancers for drug development.

Recent research points to important roles of sub-populations of cancer stem cells (CSCs) in the growth and spread of cancers. Of particular interest, CSCs are several-fold more resistant to therapeutic killing, a property likely to be related to tumour recurrence. This raises the need to discover drugs with effective actions in killing them. This effort has now been rendered more complex by the demonstration that epithelial-mesenchymal transition (EMT) reversibly switches CSCs between a sessile epithelial phenotype and a motile EMT phenotype. In these manifestations CSCs differ in their drug resistance patterns. It is further apparent that rates of phenotypic switching, and hence therapeutic responses, are influenced both by cell intrinsic factors and by stimuli from the tumour microenvironment.

Currently, tumour transplantation to mice is considered the "gold standard" for studies of the properties and therapeutic responses of CSCs. This is based in the assumption that environmental requirements for stem cell survival are too complex to be adequately modeled in vitro. However, mouse models are far from perfect and basic CSC properties, including therapeutic resistance and entry into EMT, are retained even in standard 2-dimensional cultures on plastic. 3-dimensional co-culture of human tumour cells with fibroblasts results in interactions and cellular changes that even more closely mimic those occurring in the in vivo situation. To generate efficient in vitro stem cell assays to replace animal transplantation, we propose to (a) generate a heterotypic 3D culture system, containing both tumour and stromal cells, in which the cellular responses associated with EMT mimic those present in vivo, (b) develop EMT reporter systems enabling rapid analysis of cellular responses to known inducers/blockers of EMT, (c) assess the utility of this system for high throughput assays of agents suitable for the control of EMT and for killing CSCs in their various phenotypic manifestations.

The Mackenzie lab is located within the modern, futuristic Blizard Institute, on the Royal London Hospital campus. The Blizard Institute hosts 400 researchers with a strong emphasis on cell and molecular science. It has well equipped laboratories and the latest state-of-art FACS, high-content and high-throughput confocal microscopy equipment, and other core services.

The post is full time for three years. Starting salary will be in the range £30,805 - £34,283 per annum depending on prior accomplishment and experience inclusive of London Allowance. Benefits include 30 days annual leave, defined benefit pension scheme, and interest-free season ticket loan.

Candidates must be able to demonstrate their eligibility to work in the UK in accordance with the Immigration, Asylum and Nationality Act 2006. Where required this may include entry clearance or continued leave to remain under the Points Based Immigration Scheme.

Any specific questions about the project for other informal enquiries should be addressed to Professor Ian Mackenzie (i.c.mackenzie@qmul.ac.uk) or 0207 882 7159.

Details about the Blizard Institute can be found at www.blizard.qmul.ac.uk.

Application enquiries should be directed to recruitment@qmul.ac.uk 

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