I am a molecular biologist interested in understanding how cells are able to actively kill themselves, and how cells make the decision to live or die. Understanding how cells kill themselves will ultimately lead to better therapies designed to kill cancer
Role Of Transformation And IAPs In Sensitivity Of Cells To TNFalpha
Funder
National Health and Medical Research Council
Funding Amount
$505,786.00
Summary
Current cancer treatments are ineffective and unpleasant for patients. This is because existing cancer treatments target normal as well as cancer cells. New anti-cancer drugs have been designed to encourage cancer cells to kill themselves, by a process called apoptosis, but may still target normal cells. This project aims to discover why cancer cells are susceptible to a novel anti-cancer drug and a natural ligand called TNF but normal cells are not. This will lead to better treatments.
Apo2L/TRAIL Killing Of Tumour Cells And The Role Of Inhibitor Of Apoptosis Proteins
Funder
National Health and Medical Research Council
Funding Amount
$390,321.00
Summary
Melanomas and Gliomas are tumour types that respond poorly to current treatments. Current treatments are not only sometimes ineffective, but also unpleasant and may cause co-lateral damage. We will test 2 new targetted anti-cancer treatments, that so far appear to have minor side effects in small animal models, on these difficult to treat tumour types to see if and how they kill them. We also want to know whether these independent treatments can work together to kill tumours more effectively. Al ....Melanomas and Gliomas are tumour types that respond poorly to current treatments. Current treatments are not only sometimes ineffective, but also unpleasant and may cause co-lateral damage. We will test 2 new targetted anti-cancer treatments, that so far appear to have minor side effects in small animal models, on these difficult to treat tumour types to see if and how they kill them. We also want to know whether these independent treatments can work together to kill tumours more effectively. Although we will not personally test these drugs in clinical settings, these drugs or similar are currently in preclinical and clinical trials. This means that understanding how these drugs function is of paramount importance and may result in better clinical trials and possibly more rapid acceptance of the use of these drugs in patients.Read moreRead less
Dissecting BAFF Receptor Signals: Key Mediators Of B-Lymphocyte Survival And Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$376,165.00
Summary
B-Cells of the immune system need a growth factor named 'BAFF' to grow and survive. Elevated levels of BAFF have been detected in patients suffering from autoimmune diseases like lupus and arthritis, and B-Cell cancers like myeloma. This study will determine the identity of the chemical messages that BAFF sends to B-Cells, and how these facilitate B-Cell growth and survival. This will provide a framework for the design of targeted drug therapies that reduce the severity of BAFF related diseases.
The C-type Lectin, Mincle, Is A Macrophage Receptor For Candida Albicans.
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
The yeast Candida albicans is an important opportunistic infection that causes both mucosal and disseminated disease in patients whose innate or adaptive immune responses are impaired Infection and proliferation results in fungal colonisation of the tissues, and a variable degree of tissue damage. The latter is determined both by the virulence properties of the organism and by the genetic makeup of the host. This large, extracellular pathogen is eradicated from the body predominantly by acavenge ....The yeast Candida albicans is an important opportunistic infection that causes both mucosal and disseminated disease in patients whose innate or adaptive immune responses are impaired Infection and proliferation results in fungal colonisation of the tissues, and a variable degree of tissue damage. The latter is determined both by the virulence properties of the organism and by the genetic makeup of the host. This large, extracellular pathogen is eradicated from the body predominantly by acavenger (phagocytic) cells, which are also important in determining the severity of the associated tissue lesions. A phagocytic cell that is central to both innate and adaptive immune responses is the macrophage, which not only takes up and kills the yeast, but also is capable of of killing and digesting it, and presenting the components to cells of the adaptive immune system. This project is based on the postulate that the outcome and severity of infection is determined, at least in part, by the early functional response of the macrophage to the overall virulence properties of the yeast. The response is initiated by interactions with cell-surface receptors, and this study will show that a novel macrophage receptor, Mincle, is an important part of the innate immune response to fungal infections. We have shown that it is associated with differences in susceptibility to yeast infections in inbred mouse strains; it can discriminate between different isolates of the yeast; and it initiates the inflammatory signalling cascade. Our project will define the specific role of this receptor in fungal infection. The results will be important in understanding the basic biology of host resistance, and will offer new opportunities for therapeutic intervention by selectively blocking or modifying different activation pathways.Read moreRead less
Pathophysiological Significance Of Reverse Signaling Through Membrane TNF
Funder
National Health and Medical Research Council
Funding Amount
$453,055.00
Summary
Cytokines are molecules produced by cells that take part in immune and inflammatory responses. They coordinate the activities of leukocytes and therefore are important in the host response against infections. However, overproduction of some cytokines, particularly tumour necrosis factor, seems to cause the deleterious consequences. Tumour necrosis factor is made by cells, particularly macrophages, T lymphocytes and natural killer cells, in two stages: first, the cytokine is exposed on the surfac ....Cytokines are molecules produced by cells that take part in immune and inflammatory responses. They coordinate the activities of leukocytes and therefore are important in the host response against infections. However, overproduction of some cytokines, particularly tumour necrosis factor, seems to cause the deleterious consequences. Tumour necrosis factor is made by cells, particularly macrophages, T lymphocytes and natural killer cells, in two stages: first, the cytokine is exposed on the surface of the cell and then it is 'clipped off' and released as a smaller, soluble form. In either form it can interact with specific receptors on other cells and, in this way, change the cells' activities. We believe that binding of tumour necrosis factor receptors to the cytokine while it is in its membrane form can also send a message backwards, into the cell bearing the tumour necrosis factor. This process, known as reverse signalling, then changes the activity of this cell. In this project we will investigate this phenomenon in detail. The results will be extremely relevant to new methods of treatment of diseases, that rely either on 'masking' tumour necrosis factor by administering soluble forms of its receptor or on blocking the release of the soluble form of the molecule from the surface of the cell. Our work will enable us to understand the consequences of these approaches more fully. We will also be looking at the role of the membrane form of tumour necrosis factor in a model of infectious disease. Influenza virus is responsible for a great deal of morbidity and mortality around the world. We, and others, have shown, in a mouse model, that some cells in the lungs make tumour necrosis factor during the course of viral pneumonia. Here we will determine whether the membrane form of this cytokine plays a role in clearing virus or causing some of the complications of this disease. This also may have relevance to other inflammatory and infectious disease.Read moreRead less
Analysis Of The Functions Of A Novel Class Of Ubiquitin E3 Ligases In TNF Signalling In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$568,861.00
Summary
The aim of this project to discover the role of a novel ubiquitin ligase complex that regulates TNF superfamily signalling. It will increase understanding of the TNF pathway and improve our ability to manipulate it pharmacologically, or otherwise, in the large number of debilitating human diseases including Rheumatoid Arthritis and Crohn's disease that result from aberrant TNF signalling. Because of the role of TNF in tumorigenesis it may also contribute to novel anti-cancer treatments.