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.
Defining The Role Of Nlrp1 And The Inflammasome In Host Defence And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$634,459.00
Summary
The immune system protects the body from invading pathogens, but it can also attack the body causing inflammatory and autoimmune diseases like arthritis and multiple sclerosis. This project will focus on the molecular regulation of the ïinflammasomeÍ, a protein complex that senses invading pathogens and triggers the immune response. Understanding the inflammasome may hold the key to a better understanding of how the good and bad functions of the immune system can be balanced to prevent 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.
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.
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
A Study Of The Function Of Neuronal Apoptosis Inhibitory Proteins (NAIP) In Innate Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$242,696.00
Summary
The innate immune system is the first line of defence against infection and cancer. Regulation of the immune system is extremely important as too little response can lead to severe infections, whilst too much response can lead to chronic inflammatory disease. This project will examine the role of �neuronal apoptosis inhibitory protein� in the immune system, which should provide information on regulation of innate immunity, as well as provide insight to neurodegenerative diseases and cancer.
Manipulating The Fine-turning Of The Innate Immune Response In Disease
Funder
National Health and Medical Research Council
Funding Amount
$938,910.00
Summary
I am an international expert on the body’s first-line defense system, the innate immune response. My Fellowship focuses on studying and manipulating innate immune molecules called interferons. My research will lead to improved management of female reproductive disease, autoimmune disorders, infections and cancer through new diagnostics and therapies targeting the interferon system. The basic knowledge I generate on regulating the immune response will be applicable to a range of medical fields.
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.