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.
Entry Requirements
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
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 (Tracy.hussell@manchester.ac.uk). Applications are invited on an on-going basis but early expression of interest is encouraged.
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