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.
A Stem Cell-specific MicroRNA-independent Function Of Drosha
Funder
National Health and Medical Research Council
Funding Amount
$637,702.00
Summary
Stem cells are responsible for producing and replenishing the ~200 specialised cell types in our body. Our goal is to understand the molecular switches that control the function of these cells. We recently discovered that the activity of certain genes within stem cells is controlled by degradation. This degradation is absolutely crucial for safeguarding the function of stem cells. This project will investigate how this novel mechanism is controlled within these cells.
Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
Molecular Pharmacology Of Chemokine Receptor Signalling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,770.00
Summary
Molecular pharmacology is the study of how hormones, neurotransmitters and pharmaceuticals interact with our cells through receptors, which transfer a signal across the cell membrane to change the function of that cell. Chemokine receptors are recognised to play a role in the development of many cancers. Understanding how these receptors work has enormous implications for improving our ability to develop better anti-cancer treatments with fewer side effects.
Understanding The Function And Regulation Of G Protein-coupled Receptor Signalosomes And Their Role As High Resolution Signalling Platforms
Funder
National Health and Medical Research Council
Funding Amount
$566,588.00
Summary
G protein-coupled receptors are specialised proteins located on the surface of cells. They are the targets of 50% of currently available pharmaceuticals, but these drugs are derived from limited knowledge of only a fraction of proteins. This proposal will examine exciting and novel properties of receptors that only occur following the assembly of the proteins into specialised networks within cells. The new information will expand our current knowledge, and facilitate future targeted drug design.
Signalosomes And Compartmentalisation In Cellular Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$473,646.00
Summary
G protein-coupled receptors are specialised proteins on the surface of cells. They are the targets of 30% of currently available pharmaceuticals. This proposal will examine exciting and novel properties of these proteins that only occur following their assembly into specialised networks in cells. The use of cutting-edge technology will allow us to understand the role of these networks in many diseases. The new information will expand our current knowledge, and facilitate targeted drug design.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
A New Paradigm For Class I Cytokine Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$954,946.00
Summary
Class I cytokine receptors include around 30 receptors with diverse functions such as controlling metabolism and inflammation. Cytokine receptors are molecular switches on cells that receive signals from other cells and transmit this signal into the cell’s nucleus to control the regulation of genes. This project will determine the molecular mechanisms involved in class I cytokine receptors and use this knowledge to develop novel ways to modulate these receptors for clinical applications.