PhD Studentship: Development of an In Vitro model of Human Otitis Media

University of Sheffield - School of Clinical Dentistry

Otitis media (OM), a group of inflammatory diseases of the middle ear, is the leading cause of paediatric surgery and the most frequent reason for the prescription of antibiotics. It can have both acute and chronic (recurrent) presentations the consequences of which often continue into adulthood and thus the consequences of OM may be life long.

This project will establish a novel in vitro model of human, primary middle ear epithelial cells (MEECs) using techniques previously established in our lab to culture cells from mice that spontaneously develop chronic middle ear inflammation (Junbo/BPIFA1 KO mice). These were differentiated in vitro and infected with NTHi. Human cells will be isolated from the middle ear lining (usually scraped off and discarded) of patients suffering the consequences of chronic OM (commonly known as glue ear) and from those with chronic OM with effusion (COME). Initial cultures will use the same conditions as those used for the mouse cells with a key outcome being a detailed characterisation of the cellular phenotype of the cells by microscopy and qRT-PCR using established markers.

Having established the model we will use it to study aspects of both infectious (using NTHi) and non-infectious OM, as well as the role of mesenchymal cells. One of the main characteristics of OM is the differentiation of MEECs into goblet cells in the middle ear leading to the formation of a mucin rich effusion that is not cleared. We will modulate the phenotype of the MEECs, through IL-13 induction of goblet cell metaplasia and NTHi infection, and thus elucidate the pathogenesis of the process. The role of excessive mucin secretion can then be compared with normal cellular morphology. Gene-editing techniques will determine the role of specific genes (identified by transcriptomics/proteomics) in the pathogenesis of disease.

The model will also provide a valuable tool to test novel compounds that may alter cellular phenotypes and modify aspects of OM.

Entry Requirements

Candidates must have a first or upper second class honors degree or significant research experience.

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Northern England