Therapeutic Targeting Of CD40L-Mac-1 In Inflammatory Disease, In Particular Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$559,642.00
Summary
Atherosclerosis is a major burden for human health resulting in myocardial infarction-stroke. We have previously identified a novel interaction between two adhesion molecules, CD40L and Mac-1, which mediates leukocyte adhesion to endothelial cells being a major determinant of atherosclerotic plaque development. We are now developing blocking peptides and recombinant antibodies thereby exploring various anti-inflammatory- anti-atherosclerotic strategies, targeting both Mac-1 and CD40L.
Genetics And Biochemistry Of Biosynthesis Of The Cell Wall Of Mycobacteria
Funder
National Health and Medical Research Council
Funding Amount
$260,831.00
Summary
Mycobacteria commolnly cause human disease. The major killer in the group is Mycobacterium tuberculosis which annually causes millions of deaths from tuberculosis (TB) worldwide. Another pathogen from this group is Mycobacterium avium which often infects immunosuppressed people such as those with advanced HIV-AIDS. Mycobacteria have evolved a specialised wall that surrounds their cells which protects them from chemical attack from antibiotics and helps them to establish infections. The major ant ....Mycobacteria commolnly cause human disease. The major killer in the group is Mycobacterium tuberculosis which annually causes millions of deaths from tuberculosis (TB) worldwide. Another pathogen from this group is Mycobacterium avium which often infects immunosuppressed people such as those with advanced HIV-AIDS. Mycobacteria have evolved a specialised wall that surrounds their cells which protects them from chemical attack from antibiotics and helps them to establish infections. The major antibiotic used for TB stops cells from synthesising the protective layer thereby making them very vulnerable to human immune defences. Unfortunately, resistance to this antibiotic is common and new antibiotics are needed to treat mycobacterial infections. We are studying how mycobacteria make the cell wall and are looking for key steps where new drugs might be able to inhibit the process. Our approach is to inactivate genes in the mycobacteria that make the enzymes which control cell wall synthesis. The gene inactivation results in crippled mycobacteria that are unable to make proper cell walls. We analyse the cell wall changes that gene inactivation cause studying the chemical composition of the cell. This helps to identify the steps in cell wall biosynthesis and each step becomes a potential target for new drugs. Each of the weaken mycobacteria can be tested to see how well they can resist antibiotics and to see if they can survive host defences. In this way we can identify which components of the cell wall are critical for them to establish infections and resist antibiotic treatments. Enzymes that participate in the synthesis of such components are prime targets for us to concentrate on to design new antibiotics.Read moreRead less
Macfarlane Adaptive Changes In HIV-1 Subtype C Envelope Glycoproteins Contributing To Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$310,787.00
Summary
HIV exists as multiple subtypes. The most commonly studied is type B (B-HIV). B-HIV is common in developed countries, but accounts for only a small fraction of HIV infections worldwide. Type C HIV (C-HIV) in Africa and Asia accounts for the majority of infections worldwide, yet very little is known about how C-HIV causes AIDS. We aim to understand how C-HIV causes AIDS. This is critical for development of drugs and vaccines specifically designed for those who are most urgently need.
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein