Regulation Of Immune And Inflammatory Responses By Short Chain Fatty Acids And GPR43
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Innate immune mechanisms provide essential signals that determine the outcome of immune responses. The identity of these innate mechanisms may provide opportunities for manipulating immune responses, or controlling inflammatory responses. This proposal centers around a new and little-studied receptor, GPR43, which binds products of bacterial metabolism. This molecular pathway may explain how diet affect immune responses.
Toll-like Receptors And Innate Immunity: Genes And Pathways Regulating Infectious And Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$138,367.00
Summary
The innate immune system is the first line of defence against infectious diseases, but also contributes to the pathology of inflammatory diseases (e.g. rheumatoid arthritis). I study specific genes and pathways used by the innate immune system to (1) understand how the innate immune system prevents infections and how microorganisms overcome these defences, and (2) develop approaches to block inflammation. Outcomes may include new therapies for inflammatory and infectious diseases.
Inhibitors Of Class II HDACs In Inflammatory And Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,774.00
Summary
Inflammatory diseases such as arthritis and inflammatory bowel syndrome are major social and economic burdens on Australian communities. Obesity, diabetes and cardiovascular disease are also now widely viewed as inflammatory diseases. New specialised types of anti-inflammatory drugs are urgently needed to treat such diseases. This project proposes to create new classes of anti-inflammatory drugs by altering anti-cancer drugs called histone deacetylase inhibitors.
New Mechanisms Regulating S100 Protein Function In Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$813,929.00
Summary
This project will examine new ways which affect the major effector cells in allergic inflammation and asthma regulated by novel S100 protein mediators. We find a natural protein (S100A12) of the innate immune system, in cells in the lungs of patients with acute asthma. S100A12 activates mast cells to release mediators that trigger asthma attack. We will characterise the proteins with which this protein binds on the cell surface and and determine how this mediates their activation.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes, Alzheimer’s and Parkinson's. This research program will reveal how the body deactivates inflammasomes – protein complexes at the heart of inflammation and disease – so we can design better drugs for treating patients with inflammation-driven disease.
Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
Structural And Functional Studies Of The Human IL-3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
This proposal will study a protein hormone that is implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine how the hormone receptor becomes activated, identify and characterise new agents that block this activation. This information will help in the development of new and highly specific drugs for use in certain cancers in inflammatory diseases.
Role For Dipeptidyl Peptidase-IV In The Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The innate immune system is the bodyÍs first line of defence in fighting off infections by invading organisms. An inappropriate innate immune response can lead to the development of several inflammatory conditions such as inflammatory bowel disease. A malfunctioning innate immune response has been identified in children with IBD. This project will determine the role of a unique enzyme called DPIV in the development of innate immune responses and its potential as a therapeutic target for IBD.
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.
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