TOLL LIKE RECEPTORS AGGRAVATE GLOMERULONEPHRITIS AND KIDNEY INJURY IN RENAL VASCULITIS
Funder
National Health and Medical Research Council
Funding Amount
$110,068.00
Summary
Anti neutrophil cytoplasmic antibody associated vasculitis (AAV) is a significant cause of morbidity and mortality. My thesis will explore the role of Toll Like Receptor (TLR) 2 and TLR9 in the initiation and pathogenesis of AAV and the therapeutic potential of TLR2/9 inhibitors. I will use both a murine experimental model and human kidney biopsy samples in this work. My thesis will further define the critical molecular events that underlie the disease whilst addressing potential new therapies.
Inflammasome Function In Protection Against Infectious Disease And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Inflammation, characterised by swelling, heat, pain and redness, is a normal response to injury and infection. Many human diseases such as gout, athersclerosis, diabetes and Alzheimer’s disease involve some inflammation, mediated through a common pathway termed the inflammasome. This project will investigate the proteins involved in this pathway and how they interact in their normal role of combatting infections, as well as a possible defect in this pathway in autoimmune patients.
PB1-F2 Is Critical To Influenza A Virus Pathogenicity Through Activation Of The Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$663,919.00
Summary
Fatal Influenza A virus infections are excessive inflammation. We identified the IAV protein PB1-F2 as critical in driving excessive inflammation via activating the host inflammasome complex. Our study evaluates PB1-F2-mediated inflammation contribution to inflammatory responses. Identifying PB1-F2 in emerging IAV strains is invaluable in aiding health policy makers to quickly assess fatal IAV pandemics. Our research will potentially identify treatment targets towards reducing this inflammation
Mammals have evolved an array of mechanisms to sense microbes. These immune sentinels must distinguish self from non-self to activate an immune response. The initiation, amplification and quenching of an immune response is carefully orchestrated to eliminate invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that prevent inflammatory diseases such as cardiovascular disease, hepatitis, inflammatory bowel disease and skin diseases.
There are two arms to the immune system, one that learns and adapts, which can cause autoimmune disease, and another that is immediate and innate, and can cause autoinflammatory disease. This proposal continues our work in the characterization of rare genetic autoinflammatory disesaes and extrapolates these studies to more common chronic inflammatory diseases. This stands to improve current diagnosis and treatment, and elucidate future drug targets that could be targeted clinically.
Transport and innate immune properties of DNA in bacterial nano-sized vesicles. All types of living organisms release nano-sized membrane vesicles or “blebs” which they use for intercellular communication and transport of molecules. This project will determine how bacteria package DNA within these vesicles, how this DNA is transported into host cells and how it triggers immune responses in these cells.
Circadian Clock Regulation Of Dendritic Cell Metabolism And Function
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Immunological and metabolic parameters change with the time of day, and are known as circadian rhythms. These fluctuations are critical for host adaptation to the environment and anticipate any increased risks of tissue damage and infection that accompany changes in activity and feeding. How the molecular circadian clock influences innate control of adaptive immunity is unknown. We will investigate how circadian proteins influence immune function through their sensing of nutrient and metabolic
Characterization Of Novel, Colitis Associated Pathobionts To Identify Therapeutic Targets In The Host Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$684,609.00
Summary
Applying cutting edge methods to grow bacteria from the human gut, we have identified three species, two previously unknown, that are found in many inflammatory diseases including Inflammatory bowel disease, colorectal cancer and in cancer immunotherapy patients who experience colitis. By characterizing these bacteria and the immune response in human cells we are seeking to discover novel targetted methods to prevent colitis and gastrointestinal inflammation.
The innate immune response is our primary defence against infection, but must be controlled carefully to avoid chronic inflammation and autoimmunity. Studying tiny regulators of gene function called micro-RNAs and unique cellular pathways, we aim to understand the “big picture” of genetic regulatory systems in innate immunity to provide new insights into inflammation and infection, the genetic basis of diseases, and to identify new potential therapeutic targets, biomarkers and antiviral targets.
A Systems-biology Approach To Understanding The Beneficial Heterologous Effects Of Neonatal BCG Vaccination In A Melbourne-based Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$846,853.00
Summary
BCG vaccine (usually used to protect against TB) also enhances the immune system of young babies to protect them against infections other than TB. We have a large collection of blood samples from a study in which babies were randomised to be given BCG vaccine at birth or no BCG. We will use these to understand the immunological and molecular mechanisms by which BCG boosts the immune system to protect against infections other than TB.