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Modelling the tumour-induced changes to the tumour microenvironment (TME) and extracellular matrix (ECM) in head and neck cancer metastasis within a defined minimal 3D in vitro environment.


   Blizard Institute

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  Dr A Biddle, Dr M Efremova  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

PhD (non-clinical) studentship; Modelling the tumour-induced changes to the tumour microenvironment (TME) and extracellular matrix (ECM) in head and neck cancer metastasis within a defined minimal 3D in vitro environment.

Applications are invited for a fully funded three year PhD studentship at QMUL, to start in April 2022. We are looking to support an ambitious student with a strong interest in using cross-disciplinary approaches to improve the experimental modelling of human cancer. This will include advanced in vitro tumour models, single cell molecular analysis, and computational approaches in order to probe how tumours condition their metastatic site. The PhD student will work with Dr Adrian Biddle in the Centre for Cell Biology and Cutaneous Research at the Blizard Institute, and Dr Mirjana Efremova at Barts Cancer Institute. 

Applicants should have a good honours degree (minimum 2(i) or equivalent) with a strong background in cell and molecular biology or a related subject. Hands-on cell culture experience would be advantageous, and an interest in developing new in vitro approaches to tissue modelling is essential.

Head and neck cancer metastasises initially via the lymphatics of the neck, before crossing into the blood vessels and spreading more distantly. Around 20% of head and neck cancers exhibit distant metastasis, most commonly to the lungs but also frequently to liver, bone and brain. They therefore encounter and colonise a variety of metastatic environments, and we do not yet know the mechanisms employed by the tumour cells to achieve this. Identifying and targeting these mechanisms could enable the development of new anti-metastatic therapies for head and neck cancer.

Human tumours exhibit striking heterogeneity in their molecular drivers and therapeutic sensitivities, which presents a huge challenge for the development of cancer therapies. However, the TME is much more consistent between tumours, with the same non-tumour cell types and ECM molecules communicating with the tumour to either promote or restrain its growth. This therefore presents an exciting avenue for potential new cancer treatments that can re-condition the TME to be hostile to tumour growth, particularly at metastatic sites. To achieve this aim, we must be able to identify the key elements from within the complexity of interactions between the tumour cells and their metastatic site. For this, we aim to develop 1) integrated models that can make testable predictions of the effects of changing individual variables within the TME, and 2) a tractable experimental system where variables can be constrained.

 Further information about our work can be found at our lab webpages:

sites.google.com/view/biddlelab-qmul/home

www.efremovalab.org

This project will utilise the excellent research infrastructure and state-of-the-art facilities of the Blizard Institute, including the new CREATE biofabrication facility (www.qmul.ac.uk/blizard/research/core-facilities/create-lab). We also have established collaborations with clinicians at Barts Health NHS Trust for the supply of human tumour tissue. The project will provide excellent training opportunities in cell biology, molecular biology, in vitro tissue modelling, and bioinformatics approaches within a supportive team to prepare the student for their research career.

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

The studentship is funded for 3 years. It will cover UK PhD tuition fees, laboratory costs and a tax free annual stipend of £17,609.

Informal enquiries about this post can be made to Dr Adrian Biddle (click on name link above).

The closing date for applications is 11th February 2022 and interviews will be held in late February / early March 2022.

Please use the following link to apply: https://mysis.qmul.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RFQM-W1XF-05&code2=0013


References

BIDDLE, A., GAMMON, L., LIANG, X., COSTEA, D. E. & MACKENZIE, I. C. 2016. Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma. EBioMedicine, 4, 138-45.
BIDDLE, A., LIANG, X., GAMMON, L., FAZIL, B., HARPER, L. J., EMICH, H., COSTEA, D. E. & MACKENZIE, I. C. 2011. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res, 71, 5317-26.
YOUSSEF, G., GAMMON, L., AMBLER, L., WICKER, B., PATEL, S., COTTOM, H., PIPER, K., MACKENZIE, I. C., PHILPOTT, M. P. & BIDDLE, A. 2020. Disseminating cells in human tumours acquire an EMT stem cell state that is predictive of metastasis. bioRxiv, 2020.04.07.029009.
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