Role Of Sphingolipid Signalling In Hepatic Insulin Resistance And Its Application In Prediction Of Risk For Type 2 Diabetes And Prediabetes
Funder
National Health and Medical Research Council
Funding Amount
$563,305.00
Summary
Type 2 diabetes is expected to reach epidemic proportions in the coming decades. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. We have identified an enzyme that plays an important role in insulin signalling. The possibility is that the level or activity of this enzyme is a potential biomarker of the prediabetes state and could be also used as a target
Control Of The Ras/Erk Signaling Pathway By The Brahma Chromatin-remodeling Complex
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Hormones bind and initiate molecular signals within cells to proliferate or change into specific cell types. This is important for growth and development of different tissues. A pathway which is critical for transmitting the effects of hormones in cells is the Ras pathway. New studies by the applicants indicate that the Brahma complex, a molecule important in controlling the levels of proteins in cells, activates the Ras pathway. This project will define how Brahma controls the Ras pathway.
Location, Location, Location: Sub-cellular Specific Targeting Of JNK As A Novel Therapy In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$633,755.00
Summary
The ‘triple negative’ breast cancer subtype is the most aggressive form of breast cancer, and unlike other subtypes, there are no drugs to specifically this subtype. While many potential drug targets have been identified, they cannot be utilised clinically because of other beneficial roles within the body. We are now deploying our innovative experimental platforms to specifically target the tumour promoting functions of a protein known as ‘JNK’, whilst retaining its beneficial functions.
This Program studies the mechanisms that control blood cell formation and how abnormalities play a role in leukaemia, a significant health problem worldwide. Despite some improvements, two major problems remain: controlling progression of leukaemia and relapse. The Program tackles these two major issues with the combination of studies of normal blood and leukaemia cell function, drug design and clinical trials ensuring a direct pathway from discovery to patient benefit.
The pathology of many acute and chronic diseases associated with the inappropriate activation of genetically encoded programmed cell death pathways, such as sepsis, stroke, diabetes and neurodegeneration, is linked to detrimental inflammation. This project will accurately define at the molecular level how programmed cell death triggers inflammatory responses, and use this knowledge to test novel and next-generation therapeutic strategies in inflammatory-driven diseases.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
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.
The cell is the building block of life. This proposal focusses on the surface of the cell, the plasma membrane, and specialised structures called caveolae that are an abundant feature of animal cells. Altered caveolae are a feature of many human disease conditions. In this proposal we will address the function of caveolae. We will test the idea that proteins are released from caveolae into the cell when cells are stressed forming a novel signalling pathway disrupted in disease.
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Molecular Dissection Of Aberrant IL6/gp130 And TGF? Signaling In The Pathogenesis Of Interstitial Pneumonitis
Funder
National Health and Medical Research Council
Funding Amount
$590,009.00
Summary
Interstitial pneumonia (IP) is frequently observed in the group of lung diseases which affect the transfer of oxygen from inhaled air into the bloodstream. Current treatments for these diseases only effectively manage patient’s symptoms but don’t cure patients of IP. We have developed a strategy to identify the exact cell type responsible for an acute IP and the molecular intermediates that may offer novel treatments and pave the way for a possible cure for this disease.