Roles Of Signalling In The Control Of Immune System Development, Function And Pathology
Funder
National Health and Medical Research Council
Funding Amount
$737,936.00
Summary
This research focuses on the function of the NF-?B and MAP kinase biochemical pathways in immune cells. Both pathways regulate gene expression controlling the development, division, viability and function of immune cells. Consistent with these roles, impaired regulation of these pathways contributes to many immune related diseases. My goal is to utilize information learnt about these pathways and apply it to developing therapies for treating diseases afflicting the immune system.
T-cells: The Key To Unlocking Immunity Against Aggressive Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
By investigating several aspects of patients’ immune defenses against the cancer cells in Diffuse large B-cell lymphoma, this project will provide critical insights on ways to harness the patient’s own immune system to effectively mount anti-tumour responses. These results will pave the way for future therapeutic strategies to successfully treat and prevent lymphoma.
Investigating Tumour Development And Metastasis Using A Novel Drosophila Cancer Model.
Funder
National Health and Medical Research Council
Funding Amount
$505,500.00
Summary
The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually opera ....The majority of cancers are derived from epithelial cells. The primary cause of cancer related deaths is due to the ability of these epithelial cancer cells to migrate and invade other tissues within the body away from their primary tissue of origin (metastasise). This proposal seeks to understand the pathways that are important in regulating the processes of epithelial cell migration and invasion that are instrumental in promoting the metastatic spread of tumour cells. As controls usually operate to induce cell death in any cell that attempts to break away and invade other tissues, this proposal also seeks to understand some of the pathways that are responsible for causing these cells to die. To carry out these investigations we have developed a novel Drosophila model of epithelial cancer development. We use this model because of the ease with which it is possible to carry out complex genetic analyses and so dissect the roles of the many different signalling pathways involved in these processes. The strength of the model is that it is dependent upon genetic alterations that are also implicated in the development and metastatic spread of many mammalian cancers, namely activating mutations in two genes, Ras and Notch. It is expected, therefore, to offer considerable insight into why these activated genes also cause the spread of cancer cells in humans.Read moreRead less
Enhancement Of Newborn Neuron Survival To Promote Repair Following Adult Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
Following brain damage tissue needs to be rebuilt and newborn nerve cells need to survive. Identification of factors that enhance the numbers and promote the survival and appropriate integration of newborn nerve cells is therefore important and over the last few years we have identified two regulatory factors that are prime candidates to enhance numbers and survival of newborn neurons following injury: the Rho pathway and suppressor of cytokine signalling-2, which we will test for effectiveness ....Following brain damage tissue needs to be rebuilt and newborn nerve cells need to survive. Identification of factors that enhance the numbers and promote the survival and appropriate integration of newborn nerve cells is therefore important and over the last few years we have identified two regulatory factors that are prime candidates to enhance numbers and survival of newborn neurons following injury: the Rho pathway and suppressor of cytokine signalling-2, which we will test for effectiveness following brain injury.Read moreRead less
Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and, in ....Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and, in general, to maintain the correct number of cells in the body. As such, misregulation of apoptosis is associated with the pathogenesis of a wide array of diseases. To understand, manage and treat disorders that result from aberrant apoptosis, we need to know at molecular and cellular level, how apoptosis is brought about and how it is regulated. We have been studying these processes in detail for several years. Central to the apoptotic execution of cell death are a group of proteases called caspases, that target many cellular proteins for specific cleavage. The activation of caspases is the crucial step in the initiation of apoptosis and therefore each cell has developed complex ways to control this process. If we understand how these regulatory mechanisms operate, we can then formulate strategies that are targeted towards pathologies involving abnormal apoptosis. In this proposal we will use vinegar fly as a model to study the function of caspases in development. We believe that results from this proposal will have several major benefits. Firstly, they will provide important insight into the mechanisms of developmental apoptosis thereby filling many gaps in our current knowledge. Secondly, the study will endeavour to identify new molecules-pathways that lead to caspase activation. Finally, the proposed studies will shed light on the function of caspases in non-apoptotic pathways.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
While most leukemia patients initially respond well to chemotherapy, >60% die because the disease returns as a result of the survival of leukaemia cells following treatment. We have identified a new protein, osteopontin (OPN), that may allow the survival of leukaemia cells and therefore reduce the ability of chemotherapy to erradicate disease. We seek to examine the role of OPN in leukemia with a view toward developing targetted therapies in the future.
RZR-alpha In The Control Of Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,706.00
Summary
Four million Australians have cardiovascular disease accounting for 35% of all deaths. CVD is the most expensive disease burden and a National Health Priority. Smooth muscle cell growth is a cause of CVD. However, the mechanisms controlling SMC hyperplasia are poorly understood. This project will provide key insights on the role of RZR-alpha in the pathogenesis of blood vessel disease, and develop novel gene-targeting approaches for new opportunities to control complications of CVD.