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This work will analyse how cells, the building blocks of tissues, are organized together to form functioning organs. It focuses on the adhesion molecules that allow cells to recognize one another, which cooperate with the internal skeleton of cells to link them together. We aim to understand how these cellular systems work normally and how they are targeted to disrupt tissue integrity in diseases like cancer and inflammation.
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.
How Caveolae Condition Tissue Mechanics For An Anti-tumor Niche.
Funder
National Health and Medical Research Council
Funding Amount
$1,091,226.00
Summary
The outcome of cancer is determined not only by the behaviour of the cancer cell, but also by how the normal tissue cells of the body respond to it. This project investigates how tissue cells that surround cancer cells can eliminate early cancers from the body. It develops on newly-discovered mechanisms that allow epithelial tissues to detect and physically expel cancer cells. This mechanism can protect us from cancer, but potentially allow cancer to develop when it fails.
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.
Characterisation Of Novel Cilia Proteins And Roles In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$339,410.00
Summary
Cilia and flagella are tiny hair-like structures attached to the surface of most cells in the body. They perform different roles in many different organs including the brain and play key roles in our sensory systems. This project aims to identify and characterise components of cilia in order to better understand the causes of disorders where the cilia do not function properly.
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.
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.
Regulation Of Dynamic Cell-cell Adhesions By Coordinated Action Of Lipid Kinases And Phosphatases
Funder
National Health and Medical Research Council
Funding Amount
$529,565.00
Summary
This research project studies the molecular mechanisms that allow cells to attach to, and recognize, one another. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside on the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, to adhere to each other. By this means, populations of individual cells can be linked together into cohesive populations - i.e. the tissues and organs of the body. The importance of cadherin adhesion i ....This research project studies the molecular mechanisms that allow cells to attach to, and recognize, one another. Such cell-to-cell adhesion is mediated by the cadherin family of molecules, which reside on the surfaces of cells. Cadherins allow cells to recognize one another and, upon recognition, to adhere to each other. By this means, populations of individual cells can be linked together into cohesive populations - i.e. the tissues and organs of the body. The importance of cadherin adhesion is exemplified by the fact that disruption of cadherin adhesion contributes to many important diseases, especially inflammation and cancer. Thus understanding how cadherins hold cells together is necessary for us to understand the molecular basis of common diseases. In this project we study how cadherins signal to regulate cellular behaviour. We build on our recent discovery that E-cadherin can activate a lipid in the cell membrane, PIP3, that is known to be a key regulator of many cellular activities. We aim to understand how this signal is generated in response to E-cadherin adhesion and how it elicits normal cellular responses to cadherin adhesion.Read moreRead less
Preserving Barriers: How Cadherin Signaling Coordinates Dynamic Adhesion And Tight Junction Assembly In Epithelial Cell.
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
Epithelia protect the body from its environment. Breakdown of the epithelial barrier in tissues such as the skin and intestine, as occurs in burns and inflammation, leads to invasion of bacteria and severe metabolic disturbances. In this project we study the cell signaling mechanisms that maintain epithelial barriers in healthy tissues that undergo turnover and remodelling. Understanding these signaling pathways provides a foundation to understand how they are perturbed in disease.