Neuronal Toll-like 2 Receptors Contribute To The Spread Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$900,010.00
Summary
How the pathological protein in Parkinson’s disease (PD), ?-synuclein, spreads through the brain remains unknown. Toll-like receptor 2 (TLR2) located on microglial cells have been identified as the receptor responsible for the internalization of ?-synuclein by this cell. We have found TLR2 in PD neurons accumulating Lewy pathologies, suggesting that neuronal TLR2 contributes to the neuronal spread of ?-synuclein in PD, a theory requiring further biological evidence prior to therapeutic targeting
Consequences Of MYD88 Mutations Commonly Found In Human B Cell Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$442,583.00
Summary
MYD88 is one of the most recurrently mutated genes in B cell malignancies, such as diffuse-large B cell lymphoma and Waldenström macroglobulinemia. This project will characterise oncogenic MYD88 mutations by introducing the mutations into normal mouse B cells. It will examine how the mutations disrupt signalling pathways and B cell functions and how the mutations respond to new lymphoma drugs. We hope this project will provide information for lymphoma pathogenesis and rational drug selection.
Intrinsic Host Antiviral Activity Against Pathogenic Filoviruses
Funder
National Health and Medical Research Council
Funding Amount
$488,754.00
Summary
Bats are a major reservoir for deadly human viruses including Ebola and Marburg virus. In contrast to humans, bats can be infected with these viruses without showing clinical signs of disease. The reason why bats can co-exist with these viruses is unknown. This study will determine if a bat antiviral molecule contributes to limiting virus release compared to the human version that could reveal strategies to prevent and control these deadly viruses in humans.
Excess inflammation is a major problem after injury and in many diseases. Upon injury molecules are release that act as danger signals to alert the immune system to start the repair process. However, high levels of these dangers signals can impair the final stages of healing. Understanding how to prevent the immune system being excessively stimulated by these danger signals is key to being able to dampen inflammation after injury improve the healing response.
How BANK1 Pathway Defects In B Cells Cause Human Lupus
Funder
National Health and Medical Research Council
Funding Amount
$1,316,839.00
Summary
Autoimmune diseases affect 1 in 20 Australians and are incurable. To find effective therapies, we need to understand the genes that cause disease in humans. We have sequenced the entire genome of patients with an autoimmune disease and found several patients carrry two mutations in genes important for activation of B cells and shown these mutations cause disease. We plan to understand how these genes prevent autoimmunity, and to identify the best treatment for patients with these mutations.
Arterial Spin Labeling Perfusion MR Imaging Of Tissue Pathophysiology In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$402,604.00
Summary
It was estimated that in 2012 there were 420,000 Australians living with disability caused by stroke. This project intends to develop a practical treatment selection approach using advanced imaging to target likely treatment responders which could result in more patients living disability free from improved diagnosis and individualised tailoring of acute interventions using MR imaging. The ultimate aim of this project is the translation and implementation of practical advanced imaging stroke.
Defining A Role For TLR7/8 In Helicobacter Pylori Infection
Funder
National Health and Medical Research Council
Funding Amount
$568,007.00
Summary
Helicobacter pylori is a bacterium responsible for chronic gastritis and is associated with development of gastric cancer. In this project, we will investigate how the immune system interacts with H. pylori during colonisation – focusing on a sensor of the immune system, called TLR8 (and its mouse equivalent, TLR7).
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Glutathione Transferase Omega 1 As A Novel Target For Sepsis And Other Inflammatory Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$694,471.00
Summary
Sepsis is a major clinical problem that causes more deaths in Australia than breast, prostate or colon cancer. The deaths result from an overwhelming systemic inflammatory response to infection. We have discovered that this response is dependent on an enzyme called GSTO1-1 and that inhibitors can block the inflammatory response . In this study we will identify new drug like compounds that can inhibit GSTO1-1 and prevent death from sepsis.
Defective Toll-like Receptor 7 Signalling In Plasmacytoid Dendritic Cells Underlies The Inception Of Virus-associated Asthma
Funder
National Health and Medical Research Council
Funding Amount
$552,301.00
Summary
In genetically susceptible individuals, respiratory virus infections are a risk factor for asthma inception and are the most common cause of acute exacerbations. Using a clinically relevant mouse model of disease, this study will investigate whether the altered expression of toll-like receptor 7, a host protein that senses viral invasion, causes the host to mount an inappropriate pro-allergic immune response to the virus.