Induction Of Islet Transplant Tolerance In A Humanised Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$374,552.00
Summary
The current treatment for type 1 diabetes (T1D) is insulin therapy, but it cannot fully prevent chronic complications. Also intensive insulin use increases the risk of fatal hypoglycemia. An emerging therapy which may overcome or at least reduce these problems is the transplantation of human islet cells. But preventing the immune system from rejecting these cell transplants is still a major challenge. This study will develop new therapeutic strategies to protect these transplants from rejection.
A New Approach To The Design And Evaluation Of T Cell Vaccines For Cancer And Infectious Disease.
Funder
National Health and Medical Research Council
Funding Amount
$394,137.00
Summary
Special white blood cells called dendritic cells teach the immune system to fight cancer and are a key component of therapeutic cancer vaccines. We identified a subtype of human dendritic cell that is predicted to be the most effective at mounting anti-cancer immune responses. We developed a novel antibody specific for these dendritic cells that can be used to deliver the vaccine directly to them and will use this to construct and validate a novel vaccine for cancer and viral infections.
Enhancing Host Defence Mechanisms In Severe Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$830,447.00
Summary
New options to treat bacterial infections are needed because of the rapid increase in antibiotic resistance. One very attractive strategy is to boost the body’s own defence mechanisms against bacteria. This project defines novel molecular mechanisms that can be manipulated to better control a bacterial infection. Novel drugs targeting these molecular pathways are already being developed, albeit for cancer. This project will help assess if these drugs may be useful to treat infections.
Immunodominance And Protective Immunity In The Context Of A Complex Host-pathogen System.
Funder
National Health and Medical Research Council
Funding Amount
$899,832.00
Summary
In experimental infection models with simple organisms, pathogen-specific immune responses recognize only a small fraction of potential epitopes encoded by the genome. This phenomenon is termed immunodominance. We propose the first comprehensive study of immunodominance in humans in response to a complex pathogen, the Plasmodium parasite that causes malaria. This will provide valuable new knowledge of host-pathogen immunity and facilitate rational vaccine design.
Translational Study Of The Genetics Of Systemic Autoimmunity Based On Mouse Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$518,500.00
Summary
Lupus is the prototypic autoimmune disease. It is characterised by inflammation that can damage virtually any organ in the body. This inflammation is the outcome of a complex interplay between the environment and genetic predisposition, resulting in production of antibodies against components of normal tissue. Better characterisation of the genetic basis of lupus is a priority because it is the single best path towards a clearer understanding of the mechanism of this debilitating disease, and ul ....Lupus is the prototypic autoimmune disease. It is characterised by inflammation that can damage virtually any organ in the body. This inflammation is the outcome of a complex interplay between the environment and genetic predisposition, resulting in production of antibodies against components of normal tissue. Better characterisation of the genetic basis of lupus is a priority because it is the single best path towards a clearer understanding of the mechanism of this debilitating disease, and ultimately, new therapeutic options. Strategies used to identify the genetic basis of human disease fall into two categories. The first involves gathering genetic information from families with more than one affected member, which is then compared with genetic information from unaffected people. This can identify genetic regions likely to contain disease-causing genes, but so far, this approach has met with limited success in lupus. Although regions of the genome that harbour disease-associated genes have been found, few actual disease causing genes have been confirmed. The second approach begins with known genes that might plausibly cause the disease, based on prior knowledge then tests are performed to see whether particular variants of these genes are more common in patients than in healthy controls. Obviously this approach is usually biased towards investigation of candidate genes that are already well-characterised. In this project, we will combine information obtained from a large-scale mouse-based programme in which genetic changes that cause features of lupus are generated randomly. In other words, there is an unbiased search for candidate genes, which should lead to the discovery of new disease pathways. Since the mouse and human immune systems are remarkably similar, genetic abnormalities that cause features of lupus in mice are highly likely to be informative about the genetic basis of human lupus, a hypothesis we will test with genetic studies in humans with lupus.Read moreRead less
Conditional Knockout Of The Murine Patched Gene For The Study Of Skin Differentiation And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$423,564.00
Summary
Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectiv ....Basal cell carcinoma (BCC) is the most common cancer in Australia. We recently isolated the BCC gene, Patched (PTCH) from analysis of patients with Naevoid Basal Cell Carcinoma Syndrome (NBCCS). Individuals with NBCCS have a wide variety of developmental defects in addition to a cancer predisposition which includes medulloblastoma, rhabdomyosarcoma and ovarian fibroma as well as multiple BCCs. This application proposes the generation of an animal model for skin development and cancer by selectively removing patched gene function from specific cell of the skin. In doing this we will be able to determine the exact role of this gene in skin development, and how mutation causes common skin cancer.Read moreRead less
The majority of stroke results from focal brain infarction, followed by substantial secondary excitotoxic damage in the surrounding areas. Tau has been shown to contribute to excitotoxicity and neurodegeneration in mouse models of Alzheimer’s disease (AD). Preliminary data show that tau reduction also protects against excitotoxic damage after experimental stroke. We aim to dissect the molecular mechanisms of stroke using a tau-deficient mouse model.
Vitamin D Synthesis Within Osteoblasts Increases Bone Mineral By Regulating Remodelling: Is This The Link Between Vitamin D Status And Fractures?
Funder
National Health and Medical Research Council
Funding Amount
$627,082.00
Summary
This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorpti ....This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorption.Read moreRead less