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The role of mitochondrial DNA-containing exosomes in communication between tumour cells and the immune system during breast cancer metastasis

  • Full or part time
    Prof J C Norman
  • Application Deadline
    Friday, January 03, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

This project will be conducted in the laboratories of Prof. Jim Norman and Dr. Ed Roberts, and will address how communication between breast tumours and the immune system can influence metastasis. The student will investigate how small vesicles called exosomes are released from breast tumours and how this can alter the behaviour of immune cells (such as T-cells, dendritic cells and neutrophils) to influence metastasis to the lymphatics and the lungs. We have found that exosomes from metastatic breast cancer cells contain mitochondrial DNA (mtDNA) which helps the exosomes to activate signalling pathways in other cells. This project will particularly focus on determining which cells of the immune system are targeted by these mtDNA–containing exosomes, and how this influences their function during tumour progression and metastasis. This interdisciplinary project will involve extensive use of genetically-engineered mouse models of breast cancer, performance of state-of-the art mass spectrometry-based metabolomics, multiparametric flow cytometry, and a range of cell biological and in vivo imaging approaches to visualise cancer and immune cell migration.

The Cancer Research UK Beatson Institute in Glasgow is one of the world-leading centres for cancer research. The Institute provides an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies with special emphasis on imaging, metabolomics and in vivo models of cancer.

To apply, please click on the ’Visit Website’ button, which will take you to the Beatson Institute website where you should fill in the application form. Please do not email your CV.

References

1. Roberts EW, Broz ML, Binnewies M, Headley MB, Nelson AE, Wolf DM, Kaisho T, Bogunovic D, Bhardwaj N, Krummel MF Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma. 2016 Cancer Cell 30:324-336
2. Dornier E, Rabas N, Mitchell L, Novo D, Dhayade S, Marco S, Mackay G, Sumpton D, Pallares M, Nixon C, Blyth K, Macpherson I, Rainero E and Norman JC Glutaminolysis drives membrane trafficking to promote cancer invasion 2017 Nat. Comms. 8:2255
3. Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, Charlton L, Knight J, Calka M, McGhee E, Dornier E, Sumpton D, Mason S, Echard A, Klinkert K, Secklehner J, Kruiswijk F, Vousden K, Macpherson IR, Blyth K, Bailey P, Yin H, Carlin LM, Morton J, Zanivan S, Norman JC. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels 2018 Nat. Comms. 9:5069
4. Torralba D, Baixauli F, Villarroya-Beltri C, Fernández-Delgado I, Latorre-Pellicer A, Acín-Pérez R, Martín-Cófreces NB, Jaso-Tamame ÁL, Iborra S, Jorge I, González-Aseguinolaza G, Garaude J, Vicente-Manzanares M, Enríquez JA, Mittelbrunn M, Sánchez-Madrid F. Priming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts. 2018 Nat. Comms. 9:2658

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