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Breast cancer electrophysiology: Understanding the function of sodium channels in tumours

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  • Full or part time
    Dr Brackenbury
    Dr Coles
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Voltage-gated Na+ channels (VGSCs) contain pore-forming alpha subunits and smaller beta subunits. The beta subunits are multifunctional channel modulators and cell adhesion molecules. VGSC alpha and beta subunits are classically known to regulate electrical excitability and migration during central nervous system development. VGSCs are up-regulated in breast cancers and promote tumour growth, invasion and metastasis. In addition, VGSCs contribute to the relatively depolarised membrane potential (Vm) that is characteristic of breast cancer cells, which may in turn regulate cellular proliferation and migration. We will test the hypothesis that VGSCs contribute to Vm depolarisation and that this in turn enables cells to migrate and invade out of the tumour. We will use tissue slices from a mouse tumour model to determine the relationship between VGSCs and Vm in tumour cells and understand how these features contribute to metastasis. Electrophysiological study of ion channel function in tissue slices is widely used by neuroscientists, but has not been applied to breast oncology, so this approach is highly novel. Using a combination of patch clamp recording, channel modulation, organotypic culture, and immunohistochemistry in tissue microarrays, we will investigate expression and involvement of VGSCs in regulating Vm and invasion. This work may uncover ion channels as novel therapeutic targets in oncology. Existing VGSC-modulating drugs, e.g. antiepileptics, may also be effective in breast cancer. There is no evidence that such drugs influence immune effector function and so they could be used to complement conventional chemotherapies and emerging immunotherapeutics.

Funding Notes

This studentship is fully funded for 3 years by Breast Cancer Now and covers: (i) a tax-free stipend at the standard Research Council rate (£14,057 for 2015-2016, to be confirmed for 2016-2017 but typically increases annually in line with inflation), (ii) research costs, and (iii) tuition fees at the UK/EU rate.

The studentship is available to UK and EU students.

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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