Several studies have demonstrated the appropriateness of 3D organoid cultures over the conventional 2D cultures, the advantages of 3D models include replicating the complex attributes of the liver beyond liver-specific metabolism, such as increased cell density, organization, and cell–cell signalling, O2 zonation.
In this project we will establish a novel in vitro 3D model to study hepatocyte biology in the context of liver disease. A more comprehensive approach to investigating the intercellular mechanisms of NAFLD will include co-culture of organoids with other cell types stellate cells, Kupffer cells, other inflammatory cells.
Aim 1: To optimise the preparation of liver organoids from mouse and human liver tissue.
Aim 2: To assess changes in cell function and signalling in response to liver injury causing agents including thioacetamide.
Aim 3: To optimise methods of optimal targeting of specific genes in the organoids.
Experiments will also aim at developing an animal model to study the mechanism and effect of loss of these proteins on systemic iron homeostasis to recapitulate the human condition that we see in our patients. In Aim 3 Potential iron overload gene variants will be prioritised and those identified through analysis of the ExAC database, and screened for in other cases of atypical iron overload present in the QIMR Berghofer HH Database.
Approaches/Skills and techniques
- Cell culture 2D and 3D
- Organoid culture
- Molecular biology
- Flow cytometry
Generation of 3D organoid cultures from human and mouse livers which can be used for understanding disease mechanisms and be used for drug and therapeutic testing.
Required skill and experience
Candidate interested in learning and utilizing a range of molecular, cellular approaches and novel animal models of disease to understanding iron-related disease. These approaches can be used for virtually all genetic disorders.
Contact the supervisor for more information.