Identifying new metabolic targets for drug discovery in breast cancer stem cells (CSCs)

Applications are invited for a fully-funded PhD studentship position, sponsored by industry. The successful candidate will work in the laboratories of Professor Federica Sotgia and Professor Michael Lisanti and collaborators within Translational Medicine.

Cancer stem cells (CSCs) are tumor-initiating cells (TICs) that appear to be the biological basis of treatment failure, due to tumor recurrence and distant metastasis, ultimately leading to poor clinical outcome in cancer patients. As a consequence, new therapies are urgently needed, to specifically target and eradicate CSCs. Circulating tumor cells (CTCs) also directly share many key functional properties with CSCs.

Interestingly, recent studies indicate that one unique feature of CSCs is a characteristic increase in mitochondrial mass, which may reflect a more strict dependence on mitochondrial function or OXPHOS. Several independent lines of evidence support the idea that increased mitochondrial biogenesis or higher levels of mitochondrial protein translation may occur in CSCs. For example, unbiased proteomics analysis directly shows that mitochondrial mass is elevated in CSCs.

Moreover, MitoTracker (a fluorescent mitochondrial dye) can be used successfully as a marker to identify and purify CSCs. Specifically, the “Mito-high” cell population showed the greatest capacity for increased i) anchorage-independent growth and ii) tumor-initiating ability in vivo.

The above findings immediately suggest a new approach for the eradication of CSCs, via the development of novel mitochondrial inhibitors.

The molecular relationship between CSCs, ageing and cellular senescence will also be explored.

The laboratory will provide all the necessary training, which will include:
1. Growth of human breast cancer cell lines in culture.
2. Purification of cancer stem cells.
3. Metabolic phenotyping: measurement of glycolytic and mitochondrial activity.
4. Drug discovery, via phenotypic drug screening.

Applicants should hold (or expect to obtain) a minimum upper-second honours degree (or equivalent) in biological sciences. A Masters qualification in a similar area would be a significant advantage.

Start date: 24th September 2018
English qualification required: EU applicants require IELTS 6.0 with no element below 5.5
Applications can be made online through the link below:
http://www.salford.ac.uk/study/postgraduate/applying/applying-for-research

For enquires regarding the application process please contact:
Catriona Nardone- [Email Address Removed] 0161 295 3482