Study level

PhD

Master of Philosophy

Honours

Faculty/Lead unit

Topic status

We're looking for students to study this topic.

Supervisors

Dr Gautam Rishi
Position
Research Associate
Division / Faculty
Faculty of Health
Professor Nathan Subramaniam
Position
Professor in Biomedical Sciences (Molecular Medicine)
Division / Faculty
Faculty of Health

Overview

Liver disease is an increasing burden on society, accounting for more than 2 million deaths worldwide. Peroxisomes are multifunctional cellular organelles which are highly enriched in the liver. Our preliminary data shows that defects in a peroxisomal protein affects the ability of the liver to respond to toxic insults. In this research proposal, we build on these important and exciting findings to examine the relationship between peroxisome dysfunction and liver disease.

Aim 1: To examine the expression and function of peroxisomal proteins in the liver.

Aim 2: To specifically deplete peroxisomal proteins in the hepatocytes of mice and examine its effect on liver function and disease progression.

Aim 3: To analyse markers of peroxisomal disorders and peroxisome gene variants in a well-defined cohort of patients with fatty liver disease.

In the proposed research, we will identify the cellular roles of peroxisomal proteins in the hepatocytes and their importance in progression of liver disease. The first two aims of the project are to examine the expression of these proteins in the specific cell-types of the liver and examine the consequences of depletion of these genes in vitro on markers of liver disease and iron metabolism. We will use high throughput next generation technologies to identify transcriptomic and proteomic changes in these models to further delineate the molecular mechanisms underlying the role of these protein in liver disease progression. In the third we will develop a genetic panel to be used to identify variants in genes known to affect the progression of liver disease to be used clinically.

All resources, equipment and facilities required for the successful completion of the proposed research project are available including animal and cell culture facilities, microscopes, real-time PCR instruments, FACS and histochemical facilities. Knockout mice and conditionally deleted mice are already breeding and the murine models of liver disease are routinely used in the laboratory. This project has the potential of developing into a PhD project.

Approaches/Skills and techniques

  • Cell culture
  • Microscopy
  • qRT-PCR
  • Histology
  • Flow cytometry
  • Next generation sequencing
  • Bioinformatics

Outcomes

Understanding the relationship between peroxisome dysfunction and liver disease with the aims of developing diagnostics and therapeutics.

Required skills and experience

Candidate interested in learning and utilizing a range of molecular, cellular approaches and novel animal models of disease to understanding liver pathobiology.

Keywords

Contact

Contact the supervisor for more information.