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The role of oesophageal submucosal glands in epithelial homeostasis and the development of Barrett’s oesophagus


Project Description

Barrett’s oesophagus, the premalignant precursor of oesophageal adenocarcinoma, is a metaplastic condition where the normal stratified squamous epithelium that lines the oesophagus is replaced by an intestinal-like columnar epithelium. Barrett’s oesophagus arises as a result of chronic reflux but the cellular origin of the intestinal-like metaplastic cells that characterise this condition is contentious. The current prevailing view, based almost exclusively on rodent models, is that they arise from cells residing at the squamo-columnar junction, where the oesophagus joins the stomach. However, using pig oesophagus (which is structurally more similar to human oesophagus than rodents) as a model, we have shown that specialised glands in the oesophageal sub-mucosa contain progenitor cells that we believe are responsible for the maintenance of the normal squamous mucosa and may also be the potential cell of origin of Barrett’s oesophagus in humans.

This project will define the heterogeneity, hierarchy and functional relationships of cell populations in these glands at the single cell level to identify these progenitor cells, and use our novel organoid culture systems to demonstrate their potential to differentiate into either normal squamous epithelium and/or Barrett’s-like intestinal epithelium. The study will also investigate the ability of acid and bile (components of refluxate) and/or inflammatory mediators to control the fate of submucosal gland progenitor cells thus demonstrating an important physiological role for the submucosal glands and providing important new knowledge about the mechanisms of both normal oesophageal homeostasis and the development of Barrett’s oesophagus.

Research in the Phillips laboratory is focused on gastrointestinal cancers and has two major themes: Barrett’s oesophagus/oesophageal cancer and phosphoinositide 3-kinase (PI3K) mutations. These themes are unified by the use of in vitro and in vivo models to address key issues in the biology and treatment of cancer and are supported by a broad skill base in cellular, molecular and translational biology.
https://www.petermac.org/research/labs/wayne-phillips

Peter MacCallum Cancer Centre in Melbourne Australia’s only public hospital solely dedicated to cancer, and home to the largest cancer research group in Australia. Cancer is a complex set of diseases, and modern cancer research institutes such as Peter Mac conduct research covering a diversity of topics that range from laboratory-based studies into the fundamental mechanisms of cell growth, translational studies that seek more accurate cancer diagnosis, clinical trials with novel treatments, and research aimed to improve supportive care.
https://www.petermac.org/education/research-education

All students engaged in postgraduate studies at Peter Mac are enrolled in the Comprehensive Cancer PhD (CCPhD) program, regardless of which university they are enrolled through. The program is managed by the Sir Peter MacCallum Department of Oncology (The University of Melbourne), based at Peter Mac.

The Comprehensive Cancer PhD program builds on established conventional training for cancer research students providing a coordinated program of skills, research and career training in addition to usual PhD activities. The program is designed to complement existing PhD activities and provides opportunities to develop professional skills that will help candidates to fulfil their career ambitions.
https://www.petermac.org/education/comprehensive-cancer-phd-program

Funding Notes

All PhD students at Peter Mac must have a scholarship from The University of Melbourne or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.

For further information about the university application process, see:
View Website

For further information regarding scholarships (both local and international), see:
View Website
Closing dates for applications for scholarships to commence in 2020: Round 1 -31 October 2019; Round 2 - 31 Jan 2020; Round 3 - 15 May 2020.

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