A DENDRITIC SUBSTRATE FOR THE CHOLINERGIC CONTROL OF NEOCORTICAL OUTPUT
Funder
National Health and Medical Research Council
Funding Amount
$898,340.00
Summary
The forebrain cholinergic system controls neocortical activity and cognitive function. This project will investigate the mechanisms by which the cholinergic system controls neocortical circuit activity in rodent models using advanced optical and electrical recording methods. The results will provide a foundation for the understanding of how dysfunction of the cholinergic system results in cognitive decline in humans, and identify new targets for improved treatment of human cognitive impairment.
Multi-centre, Multi-disciplinary Study Using A Systems Biology Approach To Investigate Immunomodulation In Children With Acute Wheeze
Funder
National Health and Medical Research Council
Funding Amount
$1,895,107.00
Summary
The concept that immunomodulation using naturally-occurring bacterial agents can treat asthma has reached international prominence. This is backed by strong epidemiologic and clinical trial data. However, detailed knowledge of the immunological mechanisms involved is essential to allow more focused therapeutic agents to be developed. The proposed multi-disciplinary immunomodulation study in 200 children aims to provide this essential information using an advanced systems biology approach.
The Differential Contribution Of Programmed Death-1 Ligands To Malarial Immunity
Funder
National Health and Medical Research Council
Funding Amount
$327,784.00
Summary
This research aims to understand how the Malaria parasite, which causes one of the world’s deadliest diseases, evades immunity. It will provide a significant advance in our knowledge of immunity against malaria and impact on current strategies to develop an efficacious vaccine or treatment for malaria.
ABCA1 _ An Intersection Between Infection, Atherosclerosis And Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$653,827.00
Summary
Pathogens interfere with cellular cholesterol metabolism in order to support their lifecycle. Such interference may cause diseases not usually associated with infection, like cardiovascular disease. Restoring normal cholesterol metabolism may help treating infection and its metabolic consequences. We will investigate molecular, cellular and physiological mechanisms of interaction of pathogens with cholesterol metabolism to find a key point that can be targeted for therapeutic intervention.
Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
How Does Disruption Of Serinc1 Expression Affect Lymphocyte Function And The Development Of Autoimmunity?
Funder
National Health and Medical Research Council
Funding Amount
$681,555.00
Summary
Autoimmune diseases affect up to 8% of the population. We have recently discovered a novel gene mutation in mice that results in increased levels of anti-nuclear antibodies, a hallmark of various autoimmune diseases in humans. The mutated gene, Serinc1, has not been previously implicated in autoimmune disease, but it is important for synthesis of key molecules in immune cells. This research proposal aims to determine how disruption of Serinc1 contributes to the development of autoimmune disease.
The Role Of Cytokines In Tumor-induced Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$754,473.00
Summary
Cancer-induced immune suppression is a major obstacle to the effective treatment of many cancers. We have shown that the cytokine IL-23, plays an important role in cancer initiation, growth and development. My project aims to characterize the cells that produce IL-23 in the cancer microenvironment and define how it suppresses cells of the immune system. A greater understanding of this cytokine’s mechanism of action will enable the rational improvement of treatments for patients with cancer
Molecular Characterization Of SEIPIN Function: Implications For Lipogenesis And Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$767,468.00
Summary
Obesity and type II diabetes have become a major health threat to Australians. This project aims to understand how fat is made and stored. Results from this research may lead to novel therapeutic strategies against obesity and diabetes.
Role Of ABCA8 Transporter In Oligodendroglial Lipid Regulation And Multiple System Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$651,516.00
Summary
Multiple system atrophy (MSA) is a rapid-onset brain disorder impacting on multiple functions of the body resulting in death. The cause of MSA is unknown and there is no cure. In MSA brains, the oligodendroglial cells are impaired and cannot properly make myelin (specialized lipid membrane), which is required for the proper functioning of the nerve cells in the brain. The aim of this project is to find out how changes in lipid in the brain impact on the MSA disease process.