Modulating Immune Responses By Targeting Dendritic Cells Using Dendritic Cell Specific Markers.
Funder
National Health and Medical Research Council
Funding Amount
$197,750.00
Summary
The ability to modulate immune responses would have major health benefits. Dendritic cells (DC) are key regulators of the immune system. Different types of DC possess different cell surface molecules and have differing regulatory functions. We have identified four novel DC surface molecules that can be used to target different types of DC. We aim to use antibodies against these molecules to either enhance the effectiveness of vaccines or to suppress autoimmune diseases.
Biological Membrane Transporters: Delivery Of An Oligonucleotide Inhibitor Of Vascular Endothelial Growth Factor (VEGF)
Funder
National Health and Medical Research Council
Funding Amount
$99,750.00
Summary
Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration, is the major cause of blindness in the developed world. Gene therapy could be a cure for this disease if the problems associated with the delivery of DNA could be addressed. Our project involves a highly novel strategy for gene delivery involving ion pair formation of lipophilic dendrimers (tree-like compounds with positive charges on the surface). We will develop new DNA-dendrimer complexes and test ....Choroidal neovascularisation, which is the most severe form of Age Related Macular Degeneration, is the major cause of blindness in the developed world. Gene therapy could be a cure for this disease if the problems associated with the delivery of DNA could be addressed. Our project involves a highly novel strategy for gene delivery involving ion pair formation of lipophilic dendrimers (tree-like compounds with positive charges on the surface). We will develop new DNA-dendrimer complexes and test them in a well established animal model for neovascularisation. Successful completion of this project might offer a potential therapy for choroidal neovascularisation, with a good chance of entering into human clinical trials.Read moreRead less
Production Of A Novel Humanised Anti Dendritic Cell Therapeutic Antibody For Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$202,500.00
Summary
A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be use ....A transplant of bone marrow or other source of blood stem cells from a donor is often used to treat leukaemia patients whose disease has failed to respond to chemotherapy. The Mater Medical Research Institute has developed a world first dendritic cell depleting therapeutic antibody which may open a new strategy for the control of acute graft versus host disease, which is a very common and often fatal complication of bone marrow transplantation. The new antibody treatment is also likely to be useful for the prevention of rejection in solid organ transplantation. If successful, it will selectively control graft versus host disease, without compromising the essential anti-viral immunity and desired anti-leukemia activity of the graft.Read moreRead less
Development Of Inhibitors Of PKCzeta For Targeting Vascular Leak
Funder
National Health and Medical Research Council
Funding Amount
$335,113.00
Summary
Vascular leak (permeability) is a chief pathophysiological mechanism of many inflammatory diseases and cancer. Effective methods of reducing vascular permeability are likely to reduce or prevent morbidity. At present there are no potent broad spectrum inhibitors of vascular permeability. This application focuses on the development of such inhibitors.
Cellular And Molecular Mechanisms Of Transcutaneous Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$190,490.00
Summary
Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein ( ....Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein (cytokine) called tumour necrosis factor (TNF). TNF is known to activate specialised immune cells within the skin (Langerhan's Cells ) and we hypothesise that the interaction beween CT and LC via TNF is the pathway to the potent immune response. In this project we propose to investigate the cells and molecules involved in the immune effects of CT in the skin with a view to the development of new skin based vaccine strategies.Read moreRead less
The majority of deaths from cancer are due to metastasis, which is the formation of secondary tumours at sites remote from the primary tumour. Metastasis involves conversion of some tumour cells to an invasive, migratory form in a process that is controlled by small genetic regulators known as microRNAs. In this project we will conduct experiments aimed to provide a proof of principle demonstration in mice that microRNAs can be used to block the formation of metastases.
Development Of Novel Methods For Non-invasive Measurement Of Cardiac Output And Lung Volume During Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$257,970.00
Summary
In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse ox ....In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse oximetry during every anaesthetic, but blood flow is not. Cardiac output is measured in only a very small proportion of anaesthetised patients using intravenous catheters that pass through the heart to the lungs. This procedure is invasive and is associated with significant morbidity and mortality. At present there is no easy way to monitor cardiac output non-invasively during anaesthesia. Our proposed research project, currently underway in conjunction with an industrial partner, is aimed at the development of a reliable, rapidly repeating, non-invasive method for monitoring total cardiac output and lung volume in every patient who has an anaesthetic. The purpose of the new monitor is to ensure that potential problems with oxygen supply to the tissues are detected and corrected promptly. Our new monitoring technique is computer-controlled, can function without intervention by the anaesthetist and has very few side-effects. It can be added to any anaesthetic machine. Such a measurement technique is likely to have an impact on anaesthesia similar to that of pulse oximetry in the 1980's, and, if suitably adapted, is likely to find applications in other fields, such as intensive care, sports medicine, the respiratory function laboratory and in veterinary medicine.Read moreRead less
Exploitation Of Unique Growth Factors To Develop New Products For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$132,525.00
Summary
Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro ma ....Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro maturation (IVM), which drastically reduces the use-cost of drugs and the stress to patients. However, oocyte IVM has been slow to live up to its potential and the technology is still not in widespread clinical practice, mainly due to disappointing success rates in women. We have been studying oocyte IVM in animals for many years, and have recently made a significant technological breakthrough, improving success rates by ~50%. In this field, a 50% increase in efficiency is substantial and has significant clinical and commercial application. Currently, we are the only group worldwide with this technology. Over the course of this 2-year project we will conduct follow-up experiments to refine this discovery and investigate the feasibility of using this approach to treat human infertility. We are already in negotiations with two medical device manufacturers to licence this technology. We expect that this project will lead to a series of products and technologies that will enter a clinical trial for the treatment of infertility within 2-3 years.Read moreRead less
Development Of A PET Detection System Prototype With Depth Of Interaction Capability
Funder
National Health and Medical Research Council
Funding Amount
$360,906.00
Summary
This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and f ....This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and future markets (Australia and overseas) of the newly developing PET detection sub-modules for dedicated PET scanners. Positron Emission Tomography (PET) is a functional imaging tool, which is able to quantify physiological and biochemical processes in vivo, using short-lived cyclotron-produced radiotracers. PET is emerging as an extremely important diagnostic procedure used in the early detection of cancers, neurological diseases and as an aid in treatment monitoring and drug development. The unique advantage of PET over anatomical imaging techniques, such as X-ray CT and MRI, arises from its ability to measure changes in tumour biology, at the molecular level, prior to anatomical changes in involved tissues, using trace amounts of a radiolabelled compound (radiotracer). The full potential of PET however, is not being completely utilized due to constraints within the current designs of PET scanners. When used to its full potential PET, in principle, would be an excellent diagnostic and treatment monitoring tool for breast cancer, brain tumours and other neurological conditions such as epilepsy, Alzheimer's, Parkinson's disease, post stress disorder, dementia, and depression. Lack of flexibility in current PET scanner designs to date has meant that no commercial human brain or breast imaging scanners exist. Pilot project data proved the feasibility of our new flexible PET detection module design.Read moreRead less