Oesophageal mucosa sensory phenotype in patients with gastro-oesophageal reflux disease

Applications are invited for a three-year PhD studentship to support our exciting work into the pathophysiology of gastro-oesophageal reflux disease.

Up to 20% of general population suffer from gastro-oesophageal reflux disease (GORD), typically causing symptoms of heartburn and regurgitation. In 70% of these cases the macroscopic appearance of the oesophagus is normal, with no erosion or obvious inflammation (non-erosive reflux disease, NERD). The standard therapy for GORD is proton pump inhibitor (PPI) therapy. Many patients come to secondary care due to lack of response to PPI, indeed 30%-40% of patients with GORD do not respond adequately to current therapy. This has a significant impact on quality of life and healthcare costs.

In patients with macroscopic erosions and inflammation, the cause of symptoms is relatively easy to understand but in the majority with no erosions, the cause of symptoms (or lack of symptoms) is incompletely understood.

We believe that mucosal mechanisms are of fundamental to normal and painful heartburn perception. The oesophageal mucosa is the primary point of continuous exposure to luminal stimuli. We have recently changes of oesophageal mucosal sensory nerve distribution in patients reflux disease that may be of clinical importance (Woodland et al, Gastroenterology 2017). We wish to further explore mechanisms behind this, with a view to discovery of future therapeutic targets within the mucosa.

Applicants should have a good BSc Honours degree (minimum 2:1 or equivalent) with a background in scientific laboratory work. Skills in immunohistochemistry or molecular biology will be advantageous.
The aim of the project is to expand on our recent high impact human tissue work in gastro-oesophageal reflux disease. We wish to 1. Understand the different mucosal characteristics between GORD phenoptypes. 2. Understand the association between acid reflux perception and nerve location. 3. Understand the mechanisms contributing to superficiality of mucosal afferent nerves in NERD. 4. Understand the mucosal impact of treatment (successful and unsuccessful) with proton pump inhibitors (PPIs).

Techniques will involve immunohistochemistry and RNA qPCR analysis of human mucosal biopsies to qualitatively and quantitatively assess expression of inflammatory mediators and receptors. The research will be carried out at the Wingate Institute of Neurogastroenterology, and endoscopic tissue samples will be obtained from the Royal London Hospital. The project will be supervised by a clinical and scientific team led by Prof Daniel Sifrim.