Liver disease is a huge and increasing burden on society; it can be due to a number of different reasons including excessive alcohol consumption, viral infections, and non-alcoholic liver disease. Each of these causes may have a different molecular pathway of developing the disease pathology, but one common feature is there is an injury or insult to the liver. This injury then results in activation of the wound healing process; when this healing process goes awry liver disease can develop, the first stage of which is liver fibrosis. Although our knowledge and understanding of the molecular pathways involved in liver fibrosis has increased over the past few years, there is still a shortage of effective therapies.
Small molecule libraries have been previously used to try and identify anti-fibrotic molecules but these studies used indirect readouts to measure the effectiveness of the compounds. We have a unique cell line expressing green fluorescent protein (GFP) which can be effectively used to identify external/internal changes in the cells. This project will utilise these cells and natural compound libraries from Compounds Australia to identify molecules that can either increase or decrease collagen expression.
Aim 1: Identification of small naturally occurring compounds which can increase or decrease the expression of collagen.
Aim 2: Validation of target identified in Aim 1 in cells treated with fibrotic agents to examine the molecular pathways utilised by the identified targets, using qRT-PCR and western blotting.
All compounds will be tested initially to identify the effective target molecules. Cells will then be imaged for cell morphology, nuclei structure to examine the effect of the screening compounds on cell health.
This project will utilise the high-throughput imaging facilities at QUT. Instruments like the InCell Analyzer and Deltavision will be used to image collagen and other morphological features of the cell after treatment with the screening compounds. Hepatic cell lines will be utilised to examine the molecular pathways through which the targets identified. This project has the potential of developing into a PhD project.
Approaches/Skills and techniques
- Cell culture
- Cellular analysis
- Western blotting
Identification of small molecules which can be used to treat liver disease. The next stage will be pre-clinical studies and if successful clinical studies.
Required skills and experience
Candidate interested in learning and utilizing a range of molecular and cellular approaches to treating diseases.
Contact the supervisors, Dr Gautam Rishi and Professor Nathan Subramaniam for more information.