Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Profiling Global Inflammatory Signatures For GPCRs In Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$687,770.00
Summary
Macrophages are important white blood cells of the immune system. They trigger inflammatory responses to infection or injury, but prolonged inflammatory responses can lead to chronic diseases. In this project we aim to better understand how macrophages sense the outside environment, how external signals trigger inflammatory processes, how this leads to diseases such as autoimmune and inflammatory diseases, cancer and cardiovascular diseases, and how to control them with drugs.
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.
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.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action
Sphingosine Kinase As A Target For Anti-cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Sphingosine kinase is a protein involved in the development and progression of numerous types of solid tumors and leukaemias. We have recently made a major break-through by identifing how the cancer-inducing activity of sphingosine kinase is controlled. In this study we will target these control mechanisms to develop potential new anti-cancer therapies.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.
Structural And Functional Analysis Of Oncostatin M Receptor Signalling Complexes
Funder
National Health and Medical Research Council
Funding Amount
$519,284.00
Summary
Understanding how a chemical messenger selectively controls bone formation may lead to development of new therapies for osteoporosis and potentially other important diseases.
The Characterization Of A Novel Pseudokinase Regulator Of Platelet Formation
Funder
National Health and Medical Research Council
Funding Amount
$372,965.00
Summary
Mammalian cells contain a complex switchboard, which directs the cell to grow, die, multiply or move in response to external cues. When communication breaks down within the cell, diseases arise. Our studies are directed towards identifying the molecules that comprise the switchboard which directs blood cell formation. A detailed understanding of the regulators of blood cell formation will equip us with a sound starting point for designing drugs to ameliorate blood diseases.