Genetic And Molecular Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$575,947.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemic ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in a well established but poorly understood example of polygenic inherited susceptibility to autoimmune disease. Polygenic diseases are those where susceptibility is inherited in a complex way involving many different genes either acting together or in opposition, and the molecular basis for this kind of inheritance is particularly poorly understood. The project will analyse the basis for this kind of inheritance pattern by analysing the direct action of diabetes susceptibility genes at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within the T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will concepts and targets for understanding and diagnosing autoimmune diseases and for developing new drugs or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less
Mechanisms Controlling Antibody Production By Modulating B Cell Antigen Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$536,628.00
Summary
This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment, or resul ....This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment, or result in uncontrolled B cell accumulation in lymphoma, leukemia and myeloma. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components, and that B cell accumulation is tightly limited. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy, immune deficiency, or lymphoma, and that may be able to be used as drug targets to cure these diseases.Read moreRead less
Neurodegeneration In The Ageing Brain: How The Pathways Leading To Aggregated Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$12,322,838.00
Summary
The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program ha ....The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program has identified several diagnostic and therapeutic avenues which are now being developed by the Pharmaceutical and Biotechnology industries. Much more research is still required for maximizing the chances of success using these approaches.Read moreRead less
The Prevalence And Trajectory Of Kidney Disease In Urban Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$94,515.00
Summary
The Study of Environment and Aboriginal Resilience on Child Health is a major NHMRC funded project looking at the health and illness of urban Aboriginal children in Australia. By working together with Aboriginal Community Controlled Health Services across urban and large regional centres in NSW the study team hope to better understand the causes of common diseases such as kidney and heart disease, and whether these first begin in childhood.
Computational Modelling To Understand Early-stage Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Rather than attempting to reverse neurodegeneration, therapeutic strategies must target the earliest possible stages of disease, when treatments have the potential to prevent or slow down pathological progression. The proposed project will employ computational modelling using functional MRI to deliver highly efficient and sensitive markers of Familial Alzheimer’s disease and Huntington’s disease progression to inform when in the progression of disease clinical trials should take place.
The Causes, Treatment, And Prognosis Of Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$190,445.00
Summary
The thyroid gland controls body metabolism and is crucial to life. Disorders of the thyroid place a severe burden on the health system. Yet despite this, much is unknown about the causes, optimal treatments, and prognosis of thyroid disease. In this NHMRC Early Career Fellowship, Don aims to advance knowledge and improve treatments of these common conditions, focusing on thyroid cancer, Graves’ disease, and Hashimoto’s thyroiditis.
How The Environment And Epigenetics Affect The Brain Disease Gene, MAPT.
Funder
National Health and Medical Research Council
Summary
Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether thi ....Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether this process will have an impact on these diseases.Read moreRead less
Type 2 Diabetic Renal Complications And Microvascular Injury: Novel Predictors Of Onset And Progression, Mechanisms Of Association With Cardiovascular Disease And The Benefits Of Fenofibrate.
Funder
National Health and Medical Research Council
Funding Amount
$84,448.00
Summary
We will investigate the mechanisms of diabetic complications related to kidney and blood vessel disease, focusing on identifying people at greater risk and ways to improve or prevent these complications. In addition, we will look at how diabetic kidney disease affects non-kidney related problems like heart disease and examine the benefit of fenofibrate on both. This greater understanding will aid further drug development in kidney and cardiovascular diseases.