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.
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.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.
Novel mechanisms of early growth response-1 activation through the epidermal growth factor receptor. This project will expand our knowledge of how cytokines and growth factors switch on signalling pathways from the cell surface to the nucleus. Unique antibodies will characterise regulatory routes, state-of-the-art microscopy will define dynamic patterns of receptor co-assembly, and in vivo studies will show receptor crosstalk in animal models.
Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and sig ....Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and signalling pathways underlying these adaptive responses remain unclear. This project’s research could improve contractility, reduce cardiomyocyte death and define organismal adaptation to extreme environmental changes.Read moreRead less
An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enha ....An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enhance our understanding of the intersection between ion pumps and viruses.Read moreRead less
DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells ....DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells in tissue. The project is expected to advance understanding of T cell biology, and contribute to DNA nanotechnology and super-resolution microscopy whilst providing fundamental insights into antigen recognition by T cells and ultimately derive clinically relevant practical applications.Read moreRead less
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.Read moreRead less