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.
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.
Cortactin: Integrating Cadherin Signalling For Junctional Integrity
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Adhesion between cells holds the human body together and affects many aspects of our health, including normal tissue and organ function. Importantly, loss of normal cell-cell adhesion contributes to many diseases, including cancer and inflammation. One key adhesion molecule, E-cadherin, is necessary for many epithelial tissues and its function is perturbed in disease. This research project addresses how E-cadherin signals into cells to control cell-to-cell interactions.
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.
The Role Of Ap2a2 In Self-renewal Of Haematopoietic And Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$579,171.00
Summary
The daily replenishment of the blood system is dependent on the blood stem cell. A unique property of these stem cells is self-renewal where the stem cell function is preserved, whilst other daughter cells continue to divide. Our research investigates the molecular mechanisms that regulate stem cell self-renewal. This work has potential clinical application on at least two levels: expansion of stem cells for transplantation, and for attacking abnormal cancer cell self-renewal pathways.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
UNDERSTANDING FOCAL ADHESION DYNAMICS IN CELL MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$268,944.00
Summary
Metastatic (secondary) cancers are a frequent cause of patient mortality. Central to the development of metastasis is cell motility-movement. A key component of cell movement is the way that cells bind and release the extra-cellular matrix as they move. By understanding how the dynamics of cell interaction with the matrix are regulated, we will identify molecules that are critical to the development of metastatic cancer and thus novel targets for inhibition of metastasis.
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
Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Centr ....Cell death by a specialised process known apoptosis is a way of deleting unwanted and harmful cells from the body. As such, aberrant apoptosis is associated with a wide array of diseases including cancer. For example, abnormal levels of proteins that suppress apoptosis or enhance cell survival can result in cancer and often produce resistance to chemotherapy. To understand and treat cancers that result from aberrant apoptosis we need to know at a molecular level how apoptosis is regulated. Central to the apoptosis execution are a group of enzymes called caspases that target many cellular proteins for specific cleavage. In this proposal, we will investigate the function of one of the caspases (called caspase-2), in order to better understand its potential role in the apoptosis of cancer cells. A number of recent reports suggest that caspase-2 levels are reduced in many cancer cells. The human caspase-2 gene localizes to a chromosomal region frequently affected- deleted in leukaemia, and caspase-2 levels have been proposed to be predictors of remission and survival in patients with some types of leukaemia. We will study if loss of caspase-2 in cancer cells makes them resistant to killing by drugs and if mice lacking caspase-2 have an increased potential to develop cancer. Understanding caspase-2 function and its regulation is likely to provide new therapeutic opportunities and potential targets for cancer therapy.Read moreRead less
Signalling To Telomeres: Mechanisms Of Action Of TGFb
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is contro ....Cell lifespan is controlled by the enzyme called telomerase. High telomerase activity makes cell immortal as seen in cancer. We recently show that high telomerase activity can be inhibited by transforming growth factor b (TGFb). This may partly explain why TGFb inhibits cancer and induces cell ageing. This project furthers our investigation into the mechanism(s) by which TGFb inhibits telomerase. We recently noted for the first time that TGFb binds to telomerase gene directly, and this is controlled by another protein called c-myc. This work will determine how telomerase is controlled by a balance between TGFb and c-myc in order to find ways to control telomerase and therefore cancer. We will use a combination of sophisticated techniques of cell molecular biology and biochemistry to pinpoint and target different molecules implicated in the actions of TGFb. This study will serve as an important baseline for more applied research in controlling ageing and cancer from development.Read moreRead less