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.
The Role Of RYK And Eph Receptors In Developmental And Tumour Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
The formation of blood vessels (angiogenesis) is a key process in development of the embryo, wound healing, tumour formation-metastases and in the re-vascularisation of ischeamic limbs. The molecules which control these processess are slowly being characterised. In general belong to a family of molecules called growth factors and theri associated receptor present on the surface of a cell. These molecules can control the number, location and function of specific blood vessels within the body. Rec ....The formation of blood vessels (angiogenesis) is a key process in development of the embryo, wound healing, tumour formation-metastases and in the re-vascularisation of ischeamic limbs. The molecules which control these processess are slowly being characterised. In general belong to a family of molecules called growth factors and theri associated receptor present on the surface of a cell. These molecules can control the number, location and function of specific blood vessels within the body. Recently we have discoverd new members of a family of growth fcators called vascular endothelial growth factors, and demonstrated their ability to promote the growth of blood and lymphatic vessels. In this study we set out to examine the role of another family of growth factor receptors, called RYK (for which we have a granted patent in the USA and Australia) in angiogenesis. functional experiments in mice have demonstrated that RYK can associated with a family of receptors called Eph receptors which play a key role in the remodelling of blood vessels during development and injury. Studying these molecules may tell us why blood vessels know' to be in the correct locations in the body and why in certain disease we see vessels of incorrect structure or location. These studies will form a basis of knowledge to develop rational means to manipulate blood vessel formation in the body, using non-surgical methods. The work will also have application to the areas of cleft palate, craniofacial abnormalities and axon pathfinding.Read moreRead less
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.
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.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Characterising The Novel Signalling Mechanism For A New Interferon
Funder
National Health and Medical Research Council
Funding Amount
$525,485.00
Summary
We have discovered a new regulatory protein called interferon epsilon, made in the female reproductive tract and is crucial for protection against bacterial( Chlamydia) and viral (Herpes Simplex Virus) infections. However, we are yet to understand how it interacts with target cells. This grant will study how IFN? binds to cells and the nature of the signals it transmits. This will help us understand its role in disease and its clinical potential
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.
Understanding The Physiological Consequences Of Biased Signalling Mediated By The Glucagon-like Peptide-1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,508.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs targeting this receptor is challenging as activation by different ligands can result in distinct signalling biases, a paradigm for which there is limited understanding of the physiological consequences. This project will address this critical knowledge gap and may allow for development of novel drugs with improved therapeutic outcomes.
Unlocking The Secrets Of Royal Jelly: From Recent Breakthroughs To Novel Drugs Targeting Anaplastic Lymphoma Kinase
Funder
National Health and Medical Research Council
Funding Amount
$348,763.00
Summary
Nature is a source of incommensurable chemical diversity that throughout history have provided many useful bioactive compounds including anti-cancer drugs. Our recent results suggest that honeybees use royal jelly to regulate the expression of genes implicated in certain types of human cancer.The aim of this study is to identify inhibitors of cancer related genes in royal jelly and to understand the mechanism of their action. Our results could lead to novel combination therapies.
Insulin Regulated Aminopeptidase: A New Cardiovascular Target
Funder
National Health and Medical Research Council
Funding Amount
$672,650.00
Summary
Cardiovascular disease, leading to heart attack or stroke is the largest cause of death in Australia. We have evidence that inhibition of a newly described enzyme (IRAP) by angiotensin IV is protective in a model of atherosclerosis. Excitingly we have preliminary data indicating that mice deficient in IRAP have better vascular function therefore we will further investigate this as well as the effectiveness of newly developed IRAP inhibitors in preventing development of cardiovascular disease.