Aberrant Mesenchymal-epithelial Transition: A Pathogenic Mechanism In Tissue Maintenance And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$522,299.00
Summary
The causative genetic factors associated with aberrant changes of cellular properties are identified by analysing the profile and the control mechanism of gene expression. Specifically,this project will reveal how the transition of different patterns of tissue organization may be manifested in birth defects and malignant diseases.
The Role Of The Asymmetric Cell Division Regulator GPSM2 In Mammary Gland Development And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Tissues are built by small populations of progenitor cells which divide unequally to generate different cell types. Recent studies suggest defective progenitor cells are founders of some breast cancers and that progenitor-like cancer cells resist therapy to regenerate tumours. We have shown a progenitor division regulator called GPSM2 controls these cells and inhibits breast cancer. Examination of this new anti-tumour pathway promises to identify therapeutic targets for breast cancer recurrence.
Regulation Of Cell Death, Cell Survival And Ubiquitination In Normal Physiology And Disease
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
The project will investigate the functions of specific genes and pathways to understand the molecular basis of various diseases. It is based on our data that indicate new roles for (i) cell death in genomic instability in cancer, and (ii) ubiquitination in hypertension, developmental defects, kidney disease, as well as iron homeostasis. The work will lead to new understanding of human disease and discovery of potential new drug targets. It will also provide training of junior scientists.
Deciphering The Role Of Scribble In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$628,789.00
Summary
Scribble is a protein that controls the orientation and organization of all cells within our body. Mutations in the Scribble gene are found in many cancers and also in some patients with spina bifida, however how these mutations cause these diseases is not understood. Here we propose experiments that can be used to link Scribble mutations to specific cellular functions. This information will help us design new therapies to treat diseases driven by tissue disorganization such as cancer.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause which is unresponsive to current therapy. This study builds on recent work by this group highlighting the importance of a cell signalling molecule called STAT3 in the development of this disease. In particular, two cell types that utilise STAT3 signalling, epithelial cells and B cells, will be examined to see if blocking their STAT3 responses could be a novel therapeutic approach.
Myosin VI: A Novel Molecular Apparatus For Epithelial Cohesion
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Adhesion between cells holds the human body together and affects many aspects of our health including normal tissue and organ function. Conversely, loss of normal cell-cell adhesion contributes to major diseases, including cancer and inflammation. One key molecule, E-cadherin, is necessary for many epithelial organs and its function is perturbed in disease. This research project addresses how E-cadherin works with a cellular motor, Myosin VI, to maintain the integrity of epithelial tissues.
Adhesion between cells is important during health and disease. Cell-cell interactions are necessary both as the embryo forms and to preserve tissues and organs in later life. Important disease states arise when cell-cell adhesion is broken. Only by understanding the molecular mechanisms that hold cells together can we analyse how they are perturbed to cause diseases such as cancer and inflammation.