- Job Listing Date
- 4 Feb 2020
- Sydney, CBD, Inner West & Eastern Suburbs
- Work Type
- Full Time
- Education & Training, Research & Fellowships
THE CENTENARY INSTITUTE is a centre of excellence in medical research affiliated with Royal Prince Alfred Hospital and the University of Sydney.
Applications are invited from motivated individuals who wish to undertake a PhD in exciting basic research on either liver immunology (project 1, under the supervision of A/Prof Patrick Bertolino and A/Prof David Bowen) or liver fibrosis and hepatic cancer (project 2, under the supervision of Prof Mark Gorrell). More detail about the two projects is below.
Both projects will be based in the Centenary Institute, a centre of excellence in biomedical research affiliated with the Royal Prince Alfred Hospital and the University of Sydney located in Camperdown, NSW. Project 1 will be in the Liver Immunology Program and Project 2 will be in the Liver Enzymes in Metabolism and Inflammation Program. Both groups provide an outstanding research environment, including tools, mouse lines, expertise and the quality of PhD student supervision.
Each successful applicant needs to hold a PhD scholarship at the time of commencing the PhD and will receive a yearly $15,000 Joan Krefft PhD scholarship top up of their scholarship for 3.5 years. The Joan Krefft bequest to the AW Morrow Gastroenterology and Liver Centre also funds project consumables.
A primary degree and research experience.
- Project 1: some background and experience in immunology.
- Project 2: a demonstrable interest in biochemistry, cell biology or pathology.
Closing Date: 20 February 2020
Contacts for further details:
More detail about the two projects:
The liver hosts a range of tissue resident macrophages and lymphocytes with pro-immune functions (NK, NKT, MAIT, memory T cells). Although these cells play a key beneficial role in immune defense, they are detrimental in disease pathogenesis as they secrete hepatotoxic cytokines that kill hepatocytes and activate stellate cells, thus aggravating the damage inflicted to the liver by a variety of mediators (alcohol, fat, viruses, autoimmunity). In chronic injury, extracellular matrix protein accumulates, leading to fibrosis that may progress to cirrhosis, with consequent liver failure or cancer. The burden of chronic liver disease is currently soaring globally, largely due to Hepatitis B and Hepatitis C and rising obesity.
The two PhD projects will investigate the pathogenesis of hepatic fibrosis from two different angles:
Project 1: Role of T cells and macrophages in regulating fibrosis
Both T cells and macrophages are key regulators of fibrosis. Effector T cells secrete cytokines that induce liver damage and promote fibrosis, while macrophages play a critical role at different steps of liver inflammation and fibrosis. The liver contains a large number of resident macrophages that until recently were thought to be comprised solely of Kupffer cells (KCs). However, this view was recently challenged by our recent discovery of a 2nd subset of resident macrophages in the hepatic capsule (termed LCMs). Unlike KCs, LCMs are CX3CR1+ and derived from blood monocytes. The role of T cells and different macrophage subsets in fibrosis is unknown and requires elucidation. It is also unclear whether T cell responses are influenced by chronic inflammation in the diseased liver.
This project will use sophisticated imaging techniques, multicolour flow cytometry and unique transgenic mouse models and reporters to investigate how CD8 T cells and macrophages contribute to fibrosis in mouse models of chronic liver disease with relevance to human liver disease
Project 2: Role of proteases in human fibrosis
Proteases have been shown to regulate fibrosis and might play an important role in human liver diseases and the development of liver cancer. Anti-proteases could potentially be used to inhibit the fibrotic process. This project will use sophisticated proteomic analysis and other cell biology techniques to understand the role of proteases in regulating human liver fibrosis and liver cancers.
Centenary Institute of Cancer Medicine And Cell Biology is a centre of excellence in medical research affiliated with the Royal Prince Alfred Hospital and the University of Sydney located at Camperdown.
For more information about Centenary please visit our website www.centenary.org.au
The Centenary Institute supports The Centenary Institute supports Equal Employment Opportunity. We value diversity and encourage applications from women, Aboriginal and Torres Strait Islanders, people with disability, LGBTIQ individuals and applicants of diverse cultures and ages.