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Mitochondrial dynamics in cancer cell proliferation and migration


Project Description

Most cancer cells show elevated levels of reactive oxygen species (ROS) and fragmented mitochondria. Inhibition of mitochondrial fragmentation has been shown to effectively suppress tumour growth. Despite major advances in the field, progress in the translation of this knowledge towards cancer therapy has been slow. This could be attributed, at least in part, to the lack of understanding of how ROS signals mitochondrial fragmentation. Towards this end, we have recently demonstrated that TRPM2 channels, via Ca2+ and Zn2+, mediate ROS-induced mitochondrial fragmentation in human endothelial cells (Abuarab et al., Science signaling, 2017). Emerging evidence suggests that TRPM2 channels play a role in cancer cell proliferation as well as migration (Sivaprasadarao et al., Oncotarget 2017).

The aim of this project is to test the hypothesis that TRPM2/Ca2+/Zn2+ signalling plays a role in the mitochondrial dynamics of cancer cells and thereby contributes to tumor growth and metastasis. Novel chemical and biological probes will be used to determine the underlying cell biological and molecular mechanisms. The results may have implications for novel therapeutic approaches for cancer treatment.

Techniques to be used: General molecular biology, cell biology and protein chemistry techniques; CRISPR/Cas9 gene editing; confocal, super-resolution and electron microscopy; calcium imaging; in vitro and vivo models for cancer research.

Funding Notes

Project is eligible for funding under the FBS Faculty Studentships scheme. Successful candidates will receive a PhD studentship for 4 years, covering fees at UK/EU level and stipend at research council level (£14,777 for 2018-19).
Candidates should have, or be expecting, a 2.1 or above at undergraduate level in a relevant field. If English is not your first language, you will also be required to meet our language entry requirements. The PhD is to start in Oct 2018.
Please apply online here View Website
Include project title and supervisor name, and upload a CV and transcripts.

References

For publications from Sivaprasadarao’s group, visit:
http://www.fbs.leeds.ac.uk/staff/profile.php?un=phaass
For publications of Foster's group, visit:
https://physicalsciences.leeds.ac.uk/staff/174/dr-richard-foster

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

FTE Category A staff submitted: 60.90

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

Click here to see the results for all UK universities

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