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.
The overall aims of this study are to identify and characterise naturally occurring compounds that can modulate the expression of collagen. Initial screening will use a novel cell-based assay to identify and shortlist candidates from a library of naturally occurring compounds. These will be followed by validation of candidates identified in cells treated with fibrotic agents to examine the molecular pathways utilised by the identified targets, using qRT-PCR and western blotting. Subsequent studies will aim to use these compounds in pre-clinical studies.
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.
Expected outcomes will be the identification of small molecules that can be used to treat liver disease which will then proceed to pre-clinical studies and if successful, followed by clinical studies.