We have discovered that activating a cell surface protein increases blood sugar levels in mice. This might occur in diabetes and liver disease. We plan to (1) learn which activators of this protein increase glucose; (2) understand how they affect glucose metabolism; (3) study new inhibitors of this protein for blocking increased glucose production; (4) test the potential therapeutic benefits of blocking this protein in mouse models of type 2 diabetes and non-alcoholic fatty liver disease.
Defining The Function Of The Thrombin Receptor, PAR4, On Human Platelets
Funder
National Health and Medical Research Council
Funding Amount
$541,402.00
Summary
Inappropriate blood clot formation is the cause of most heart attacks and strokes, and platelets are the cells in the blood which form these clots. Drugs that block platelet function, such as aspirin, are used to prevent heart attack and stroke but are frequently ineffective. We will study the signals which control platelet incorporation into clots in order to discover improved therapeutic strategies for heart attack and stroke prevention.
Cellular Contributions To PAR-2's Essential Role In Periodontal Disease
Funder
National Health and Medical Research Council
Funding Amount
$648,786.00
Summary
Periodontal disease is a disease of the gums, which ultimately causes loss of teeth. It is a debilitating condition affecting about 20% of Australian adults. PAR-2, a receptor for protein-degrading enzymes, which is present on cells in the gums, is known to be required for development of the disease. This project will investigate the mechanism of PAR-2’s involvement in periodontal disease and provide ideas for development of treatments.
Targeting Protease Activated Receptor 2 In Immunometabolism And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$720,760.00
Summary
New approaches to prevent and treat obesity and metabolic diseases are National Health Priorities. Obesity is now recognised as an inflammatory disease. This project seeks new biomedical information to verify a new hypothesis that a protein (PAR2) on the surface of fat cells and immune cells is associated with the development of obesity and metabolic disorders.
Chikungunya Virus Disease; The Role Of Proteases And Their Receptors
Funder
National Health and Medical Research Council
Funding Amount
$682,716.00
Summary
Chikungunya virus (CHIKV) is a mosquito borne virus related to the Australian Ross River virus. The arthritic disease caused by these viruses is often poorly managed by current treatments. We have recently identified several proteins call proteases that circulate in the blood of infected people and promote arthritis. If successful the grant will provide new treatment options for these (and perhaps other) diseases using recently developed drugs that inhibit the activity of these proteases.
Capturing New Drugs That Selectively Modulate PAR2 Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$469,088.00
Summary
Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory ....Infection and tissue damage provoke acute inflammatory responses that sometimes continue unchecked, leading to different kinds of debilitating inflammatory diseases and cancers. We have discovered a new class of drugs that bind to a new target on human cells and block undesirable prolonged inflammatory responses. This project tests a new strategy to produce 'cleaner' drugs that act more selectively with fewer side effects against a new target in the treatment of arthritis and other inflammatory diseases, diet-induced obesity and cancers.Read moreRead less
Complement Inhibitors For Treatment Of Chronic Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$623,606.00
Summary
We aim to provide new therapeutic approaches to gum disease, which not only causes tooth loss, but also contributes to other diseases, such as cardiovascular disease and diabetes. We will find new methods to inhibit a system in our own bodies that contributes to inflammation and gum disease and test the effects of these methods of inhibition in disease models. In this way, we hope to lessen the burden of gum disease on the Australian population.
Flaviviral Proteases As Viable Targets For Antiinfective Drugs
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Viruses hijack the machinery and nutrients of cells they infect in order to reproduce. We will study viral enzymes (proteases) essential for virus replication, use fluorescent probes to learn where the viral enzymes hide and act in infected cells, track the passage of drugs aimed at these enzymes, design drugs to block their actions and stop virus replication, and test antiviral activity against Dengue, West Nile, Japanese Encephalitis and Yellow Fever viruses which infect millions of people.
Disruption Of Proteolytic Cascades In The Skin:towards Halting The Atopic March
Funder
National Health and Medical Research Council
Funding Amount
$388,601.00
Summary
There are over 3000 named skin disorders which range in severity from the trivial including acne, to life threatening such as skin cancer. Many skin diseases result from a lack of control over the way the skin maintains itself. Cutting the connections that hold cells together is key to balancing loss of skin cells with their continuous replacement. This project focuses on making compounds to block skin cell shedding with the longer term aim of producing novel drugs to treat skin disease.
Scabies Mite Intestinal Proteases As Targets For Novel Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$672,533.00
Summary
Scabies causes bacterial disease affecting poor people worldwide. Available therapies are limited and drug resistance is emerging. We investigate molecules that the mite needs to infest the skin, to guide the formulation and the testing of novel drugs. This will provide improved treatment of affected individuals and their families, thereby reducing the spread of scabies and bacterial infections and their devastating sequelae, particularly in Australian Indigenous communities.