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The role of the microenvironment in regulating breast cancer metastatic colonisation


Project Description

The metastatic spread of breast cancer cells and their colonisation of important organs is the cause of death in 95% of breast cancer. We recently studied the bone metastatic microenvironment (Eyre et al., Nature Communications, in press, see below) and discovered cytokines and other secreted factors determine the interactions with breast cancer cells. These factors are very important for the colonisation step that is necessary for establishment of breast cancer cells in a new environment. In the current proposed project, we intend to apply the same paradigm to other organs and their tissue microenvironment with the following objectives:

1.To determine factors stimulating breast cancer colony-forming activity which are secreted by the microenvironment.
2.Using breast cancer PDX and syngeneic mouse tumour models to discover whether the same factors are important in vivo.
3.To test inhibitors of, and/or genetically delete these pathways to prevent metastases in in vivo models.

The outcome will be the discovery of new important pathways involved in metastasis of breast cancer by studying the interactions of tissue and tumours. These pathways may be targetable by existing drugs or novel drugs in development and be translatable to the clinic to improve the therapy of breast cancer patients at risk of secondary breast cancer.

Training/techniques to be provided:
Training will be available for use of cell, colony and organoid culture from patient-derived samples to analyse stem cell activity. For both patient-derived samples and xenograft tumours, we will utilise single cell analysis, RNA and DNA sequencing, proteomics, bioinformatics, flow cytometry, histology, and advanced imaging. There will also be training in the planning and design of in vivo experiments for the study of experimental metastasis.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in biological, biomedical or biochemical sciences, or a related subject. Candidates with experience in the above techniques and/or with a strong interest in cancer biology are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Eyre R, Alférez DG, Santiago-Gómez A, Spence K, McConnell JC, Hart C, Simões BM, Lefley D, Tulotta C, Storer J, Gurney A, Clarke N, Brown MD, Howell SJ, Sims AH, Farnie G, Ottewell PD and Clarke RB (2019) Microenvironmental IL1β promotes metastatic colonisation of breast cancer cells in the bone via activation of Wnt-dependent cancer stem cell activity, Nature Communications, in press.

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