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.
Inhibition Of AMPK Signalling As A Strategy For Decreasing Appetite
Funder
National Health and Medical Research Council
Funding Amount
$644,266.00
Summary
The enzyme AMP-activated protein kinase (AMPK) has previously been implicated in mediating increased food intake in response to fasting and the appetite-inducing hormone ghrelin. In this study we propose to investigate whether inhibition of AMPK has promise as a strategy to reduce hunger in the context of dietary restriction and increases in energy expenditure, such as exercise. We will also test whether a new AMPK inhibitor has the potential to reduce appetite signalling in cells and in mice.
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.
The Role Of CCR6 In IL-17-producing CD8+ T Lymphocyte Activation And Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$514,041.00
Summary
T lymphocytes play an important role in the control of infection, but can also contribute to diseases such as autoimmune disease and cancer. This research will identify the function of a new subtype of T lymphocyte and determine whether inhibiting its function prevents disease.
The Opposing Genetic Networks Underlying Plasticity Of Humoral Responses
Funder
National Health and Medical Research Council
Funding Amount
$667,783.00
Summary
The immune system makes antibody to clear bacterial and viral pathogens. Specialised types of antibody are needed for different pathogens. This project will study genetic changes that determine the specificity of an antibody response. Regulation of these genes may prohibit production of antibodies and inflammatory mediators that attack the body rather than foreign pathogens. Understanding these processes will identify points of therapeutic intervention for patients with immune disorders.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Melanoma Resistance To Combination BRAF And MEK Inhibition Is Driven By Reprogramming Of MAPK Signaling
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK ....Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK signaling cascade.Read moreRead less