How do middle ear stem cells and the immune system interact in the pathogenesis of chronic otitis media? (360G-Wellcome-206442_Z_17_Z)

£309,724

Chronic middle ear inflammation (otitis media) poses a significant global burden of disease in adults and children leading to permanent deafness. The middle ear mucosa maintains a well-ventilated middle ear but undergoes abnormal remodelling in disease. Similar to the adult upper airway, basal cells are hypothesised to be stem cells actively maintaining middle ear mucosa. Pathological remodelling via abnormal repair pathways may underlie chronic otitis media and studying these could help understand and treat the disease. Aim: To identify and characterise the stem cell population of the middle ear in health and how maintenance of middle ear mucosa is disrupted by the immune system leading to chronic inflammatory disease. Methods: Murine and human biopsies will be grown and characterised in vitro, in 3T3 co-culture, air-liquid interface and 3D spheroid models to study differentiation and proliferation mechanisms in health and confirm markers of stem cell and cell fate. These markers will be used to perform lineage tracing in mice in healthy mice and in crosses with Junbo mouse model of otitis media. Finally, the role of the immune system, specifically the aryl hydrocarbon receptor (AhR – responsible for detoxification of pollutants that are linked to otitis media) will be studied using AhR agonists/antagonists and Ahr deficient mice crossed with Junbo mice.

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Grant Details

Amount Awarded 309724
Applicant Surname Chandrasekharan
Approval Committee Internal Decision Panel
Award Date 2017-09-30T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title PhD Training Fellowship for Clinicians
Internal ID 206442/Z/17/Z
Lead Applicant Mr Deepak Chandrasekharan
Partnership Value 309724
Planned Dates: End Date 2020-01-02T00:00:00+00:00
Planned Dates: Start Date 2017-01-02T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Geraint Rees