Phosphoinositide 3-kinase Signalling And Skeletal Muscle Mass.
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerat ....Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerationRead moreRead less
Skeletal Muscle Signal Transduction Related To Exercise, Metabolic Disease And Human Health
Funder
National Health and Medical Research Council
Funding Amount
$557,298.00
Summary
Exercise is one of the best prevention and treatment strategies for all major human diseases. Despite these well documented advantages, we still do not know exactly how exercise produces these benefits at the molecular level. A comprehensive understanding of this will lead to new avenues to treat many diseases. This project will monitor thousands of molecular changes that occur in human muscle biopsies following exercise and create the world’s first molecular blueprint of exercise.
Characterization Of A Novel IFNbeta Signaling Axis Mediated Via IFNAR1
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
Type I interferons (IFNs) play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. This project will investigate a novel IFN signaling axis that we have recently characterized that is mediated via the low affinity IFN receptor, IFNAR1. This signaling axis occurs independently of the high affinity IFN receptor IFNAR2 and contributes to lethality in a model of septic shock.
Targeting Cytokine Signalling In Systemic Lupus Erythematosus
Funder
National Health and Medical Research Council
Funding Amount
$917,626.00
Summary
Systemic lupus erythematosus is a disease where the immune system attacks normally healthy tissues. The spontaneous overproduction of signalling molecules called interferons in lupus plays an important role in the severity of the disease. We have found that two proteins, named Bcl6 and PLZF, are important in controlling the interferon response in lupus patients. We propose that identifying how these proteins act to control interferon will aid in developing new treatments for lupus.
Characterisation Of Autophagy Deficiency In Skeletal Muscle Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$956,237.00
Summary
Defects in skeletal muscle are a cause of muscle disease, and also have broad health implications for diabetes, obesity and liver disease. As such, it is important to understand the processes required for healthy muscle and how signals communicate from muscle to the liver and fat, which integrate whole body metabolism. This application examines how the cellular degradation process known as autophagy integrates these important processes by investigating a novel gene regulator of this pathway.
Protein tyrosine phosphatases (PTPs) control cell communication networks referred to as cellular signaling. This proposal is focused on understanding the roles of PTPs in cellular signaling networks perturbed in human disease & delineating novel opportunities for therapeutic intervention
Retinoic Acid Receptor-related Orphan Receptors And The Regulation Of Metabolism:insights Into Diabetes And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$760,799.00
Summary
Nuclear receptors (NRs) function as hormone dependent DNA binding proteins important in sustaining human health, highlighted by the array of medicines that target these proteins for human well being. ROR alpha is one such protein that we have shown regulates fat mass, obesity, and glucose tolerance. Obesity and diabetes are often linked with inflammation. We will examine how ROR controls inflammation during metabolic disease.
RGS5 Signalling In Cardiovascular And Smooth Muscle Cell Physiology
Funder
National Health and Medical Research Council
Funding Amount
$645,613.00
Summary
Cardiovascular diseases, including hypertension, remain one of the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in pathological vessel remodelling and in the regulation of blood pressure. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in cardiovascular disease models and regulatory pathways in cell systems.