STRUCTURAL STUDIES OF KEY REGULATORY PROTEINS OF THE COMPLEMENT CASCADE
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
This work is expected to lead to the determination of the three-dimensional shape of important immune regulatory proteins using X-ray crystallography. In this method, protein crystals are grown and their atomic structure determined by placing them in a beam of X-rays. The crystals cause the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge gained from the proteins' shape provides important insights into their biological function and form t ....This work is expected to lead to the determination of the three-dimensional shape of important immune regulatory proteins using X-ray crystallography. In this method, protein crystals are grown and their atomic structure determined by placing them in a beam of X-rays. The crystals cause the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge gained from the proteins' shape provides important insights into their biological function and form the basis for the rational design of new drugs to combat diseases. In particular, we are interested in determining the 3-D shapes of important proteins that control immunity. Sometimes these proteins can function abnormally resulting in serious diseases such as autoimmune diseases, stroke, Alzheimer's disease, heart attack, haemorrhagic shock, sepsis, adult respiratory distress syndrome, asthma and organ transpant rejection. Thus the ability to provide new drugs has important clinical ramifications in the treatment of these diseases.Read moreRead less
Role Of Complement Factor H And Related Proteins In Regulating Complement Activation And Microbial Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage ....A group of proteins in blood called Complement are activated in the presence of foreign cells or organisms and this generally results in their destruction. It is important to direct this destructive activity against foreign and not self tissue. This is achieved by a further family of proteins, including factor H, which regulate complement activity and how these proteins work is the principal focus of this project. There are many diseases in which damage results from inadvertent complement damage and the regulatory proteins have therapeutic potential in this area. In addition many bacteria and other microorganisms, which should be destroyed by complement, escape by binding regulatory proteins. Understanding how this is achieved may reveal new targets for vaccine development. Knowledge of how the production of factor H and related proteins will help understand how inflammation occurs and how it might be controlled.Read moreRead less
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.
Contribution Of Complement C5a To Neuronal Cell Death During Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$455,263.00
Summary
Ischemic stroke remains the second leading cause of death in Australia. This project aims to understand the role the innate immune system plays in neuronal cell death following ischemic stroke. We will use cellular and animal models of ischemic stroke, as well as examine patients affected by stroke, to explore and inhibit potential damaging immune factors generated by stroke tissue. By exploring these immune pathways, we aim to identify novel therapeutic targets to treat ischemic stroke.
Novel Insights Into The Mechanisms Of How Viruses Cause Arthritis-arthralgia
Funder
National Health and Medical Research Council
Funding Amount
$626,459.00
Summary
Many viruses are known to cause arthritis (e.g. HIV, hepatitis viruses, mosquito borne viruses). Symptoms of viral arthritis include joint pain, stiffness, and swelling. The mechanism of disease is poorly understood. We have developed a novel animal model of disease by which to study arthritic disease caused by viral infections. This model provides an excellent opportunity to explore the mechanisms of rheumatic disease in a complete functioning animal and to explore new treatment regimes.