Example rhd projects at tri
The following shows examples of some past RHD projects which have been conducted at TRI through our partner institutions.
Further research project options are available in many labs at The University of Queensland Diamantina Institute (UQDI), The University of Queensland School of Medicine (UQ-SoM), Queensland University of Technology Institute of Health and Biomedical Innovation (IHBI) and Mater Research (MR-UQ) based at TRI.
For further information on alternative projects please refer to the specific websites of each of these organisations.
Supervisor name and contact details: Dr Katharine Irvine [email protected] or Professor Elizabeth Powell [email protected]
Associated institution: UQ School of Medicine
Research themes:
Kidney and Liver Health
Immunology and Immune Disorders
Description:
Macrophages reside in all tissues in the body, where they detect diverse threats to our well-being and activate immunological defence mechanisms and wound healing. Although macrophages are involved in injury resolution, when these mechanisms are perturbed or overwhelmed, they can drive chronic inflammation and disease.
The liver is home to the largest resident macrophage population in the body. Macrophages are critical to liver health, as they help maintain immunological tolerance to all the foreign substances delivered to the liver from the gut and facilitate liver repair. When liver injury is too great, repair mechanisms cause scarring, which can eventually overwhelm liver function and lead to liver failure or cancer. Macrophages play a pivotal role in the outcome of liver injury, but we don't yet understand how and why the switch from resolution to chronic disease occurs.
We are investigating the phenotype of human liver macrophages, how they respond to internal and external factors that cause liver injury, how they interact with other liver cells to promote disease, and how the balance between their pathogenic and protective functions is compromised in advanced disease. Animal models of liver disease are used for mechanistic studies into specific factors implicated in human liver disease.
This research will yield vital knowledge in our pursuit of novel ways to treat liver disease and its complications. Students will interact with scientists, clinicians and patients, and be exposed to a variety of biomedical and clinical research approaches.
Several projects are possible in this area of research.
Key experimental approaches: primary cell isolation and culture, cell biology, molecular biology, flow cytometry, animal models, immunohistochemistry and histological assessment, microscopy.
Project Title: Susceptibility to Infection in Patients with Chronic Liver Disease and Ascites
Supervisor name and contact details: Dr Katharine Irvine [email protected] / Professor Elizabeth Powell [email protected]
Associated institution: UQ School of Medicine
Research themes:
Kidney and Liver Health
Immunology and Immune Disorders
Description:
Patients with chronic liver disease (from many causes, eg fat, alcohol or viral infection) frequently develop severely impaired liver function, or cirrhosis. Cirrhosis typically has a compensated phase, which is relatively asymptomatic, and a decompensated phase, which is associated with a range of complications, especially infections, and very poor clinical outcomes. One of these complications is the development of ascites, a large fluid build-up in the peritoneal cavity. Many patients develop bacterial infections in ascites fluid (known as spontaneous bacterial peritonitis), mainly via pathological translocation of bacteria from the gut, but very often it is not possible to culture the causative organism using traditional methods. By contrast, it is possible to detect microbial DNA in ascites fluid in the majority of patients, and we have recently shown that the level of microbial DNA correlates with poor clinical outcomes.
This project will employ culture-independent methods (PCR and sequencing), to characterise microbial communities in ascites fluid during disease progression in patients with decompensated cirrhosis. The phenotype and function of ascites immune cells will be investigated in parallel, to determine whether and how impaired immune function contributes to susceptibility to infection in cirrhotic patients.
This research will inform guidelines for antibiotic use in cirrhotic patients at risk of infection, and determine whether boosting host immunity could be a valuable adjunct therapy in this population. Students will interact with scientists, clinicians and patients, and be exposed to a variety of biomedical and clinical research approaches.
Key experimental approaches: primary cell isolation and culture, cell biology, molecular biology including next-generation sequencing, flow cytometry, microbiology.
Project Title: The role of hepatic progenitor cells in liver regeneration and fibrogenesis
Supervisor name and contact details: Dr Katharine Irvine [email protected] or Professor Elizabeth Powell [email protected]
Associated institution: UQ School of Medicine
Research themes:
Kidney and Liver Health
Immunology and Immune Disorders
Description:
The immense capacity of the liver for self-regeneration is a double-edged sword, because repair pathways are intimately linked to mechanisms of fibrosis and carcinogenesis. The ability to inhibit fibrosis whilst preserving regenerative capacity would represent a major advance in the pursuit of anti-fibrotic therapies. When the normal mode of liver regeneration (hepatocyte proliferation) is impaired, an alternative repair pathway involving hepatic progenitor cells (HPC) can be activated. HPC are capable of differentiation into hepatocytes, or bile duct-forming cholangiocytes, to replace injured cells. HPC activation and a bile ductular reaction (DR) at the periphery of portal tracts are common responses to chronic liver injury, and are thought to precede the development of progressive fibrosis. The DR consists of small biliary ductules, surrounded by an inflammatory niche. Factors secreted within the niche influence HPC activation and fate, which in turn may determine the balance between liver repair and fibrogenesis. The causal relationship/s between HPC activation, fibrosis, regeneration and carcinogenesis are quite controversial, and many important mediators remain to be discovered. Studies in animal models of CLD have provided valuable insight into the complex cross-talk driving HPC activation, but the relevance of these studies to human disease is unclear, as the human HPC niche remains relatively poorly characterised
This research project will investigate human liver progenitor cells and their niche, to identify key mediators of progenitor cell activation and differentiation. Complementary mechanistic studies in animal models will determine the role of specific cellular and molecular mediators involved in HPC activation and liver disease progression.
This research will yield vital knowledge in our understanding of liver disease progression, and our pursuit of novel ways to treat liver disease Students will interact with scientists, clinicians and patients, and be exposed to a variety of biomedical and clinical research approaches.
Several projects are possible in this area of research.
Key experimental approaches: immunohistochemistry and histological assessment, microscopy, primary cell isolation and culture, cell biology, molecular biology, flow cytometry, animal models.
