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Basal stem cells in the lung and their recognition of dying cells

Project Description

Stem cell division and differentiation is critical for barrier repair following inflammation, but the initial trigger for this process is unknown. We have defined that sensing of dying cells by the TAM receptor tyrosine kinase Axl is a critical indicator for airway stem cell expansion that drives cell cycle re-entry and symmetric cell division. However, once the pool of airway stem cells has expanded, silencing of Axl is required for differentiation.

Genetic depletion, RNAi-mediated silencing or small molecule inhibition of Axl triggers asymmetrical cell division leading to epithelial repair and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia and continued turnover of dying cells.

What we require now is to translate these findings into human lung disease. Using cardiothoracic lung resection material we will isolate basal stem cells and profile phosphatidylserine recognising receptors on their surface. The functional implications of signalling through these receptors will be determined by analysing basal cell proliferation, cell fate decisions and response to environmental conditions in health and disease.

The successful candidate will gain expertise in basal cell identification, culture and differentiation. The student will gain extensive experience of flow cytometry, tissue culture techniques, molecular biology with CyTOF and single cell sequencing where appropriate in the project.

Candidates must hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in a subject relevant to immunology and/or stem cells. Prior laboratory experience and/or an MSc in an appropriate subject area would be an advantage.

This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/ sponsorship and is due to commence from January 2017 onwards.

Any enquiries relating to the project and/or suitability should be directed to Prof Hussell (). Applications are invited on an on-going basis but early expression of interest is encouraged.

Funding Notes

This project has a Band 2 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).

Informal enquiries may be made directly to the primary supervisor.

How good is research at The University of Manchester in Biological Sciences?

FTE Category A staff submitted: 144.55

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