Transforming growth factor β (TGFβ) and its family members is involved in many phases of liver disease development and iron regulation. We have identified unexplored players in liver disease and iron-related disorders: TGF signalling intermediates. In this project, we build on our exciting findings to examine the molecular mechanisms involved in TGF signalling intermediates-mediated disease progression and their potential as targets for liver and iron-related disease.
Aim 1: To examine the expression of TGF signalling intermediates in the liver.
Aim 2: To specifically deplete TGF signalling intermediates in liver cells and examine consequences on liver disease and iron-related disease markers.
Aim 3: To generate liver cell-specific deletions in mice and examine consequences on liver disease and iron-related disease markers.
Aim 4: To identify TGF signalling intermediates targeting molecules.
In the proposed research, we will identify the cellular roles of TGF signalling intermediates and their importance in progression of liver disease and in iron regulation and will develop and test strategies to target TGF signalling intermediates preferentially in specific cell types of the liver. 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. In the third Aim liver cell-specific deletions of these proteins in mice will be generated. In the fourth aim we will use specific siRNAs identified in Aim 1 to target these genes in vivo.
All resources, animal models, 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
- Flow cytometry
Identification of the molecular mechanisms involved in TGF signalling intermediates-mediated disease progression and their potential as targets for liver and iron-related disease.
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.
- Transforming growth factor β
- Functional genomics
- Liver disease
- Animal models of disease
- Cell biology
Contact the supervisor for more information.