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.
New Mediators Of GPCR-growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$607,842.00
Summary
Hormones bind to receptors on the surface of cells. Receptors can modify each other’s function and this “cross-talk” is important for the receptors for a peptide hormone (termed angiotensin) and a growth factor receptor (EGFR), which are major regulators of the cardiovascular system. We have identified a number of mediators of the angiotensin-EGFR crosstalk and this current grant aims to use molecular and cellular and in vivo approaches to examine the molecular basis of their actions.
The Structural Basis For Biased Agonism At The Glucagon-like Peptide-1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$872,536.00
Summary
The glucagon-like peptide-1 receptor plays an essential role in nutrient-regulated insulin release, and is a major target for therapeutic treatment of type 2 diabetes. The binding of different drugs to this receptor can promote distinct signalling profiles inside the cell that can lead to different physiological outcomes. Understanding the mechanistic basis for this will provide a framework to enable rational design of novel, better and safer therapeutics for the treatment of diabetes.
Understanding The Structural Basis For Family B G Protein-coupled Receptor Function
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins that enable communication from external signals to the inside of cells of the body. Family B GPCRs are a therapeutically important subclass of these receptors and they play crucial roles in bone and energy homeostasis, cardiovascular control and immune response. This grant will uncover fundamental knowledge on how these receptors work, and will enhance future development of therapeutics.
Cytokine-driven Allergic Inflammation: Characterization Of Two Isoform-specific Modes Of IL-3 Receptor Activation And Investigation Of New Receptor-associated Signalling Partners.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung orchestrated by immune cells which produce small proteins called cytokines thus stimulating inflammatory cell production. The cytokine IL-3 is critical for the production of basophils which have an important role in the inflammation. The project will investigate the molecular details of how the IL-3 binds to its receptor and stimulates basophil production and reveal new targets for controlling inflammation in asthma.
Characterization Of SgK269, A Master Regulator Of Growth Factor Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$623,751.00
Summary
Perturbed signaling within a cell can cause multiple diseases, including cancer. SgK269 is a scaffold protein involved in signaling and implicated in breast, colon and pancreatic cancer. By determining the signaling mechanism and function of the SgK269 scaffold, this work will provide novel and important insights into a key regulator of cell signaling, and reveal potential strategies for therapeutic targeting of the SgK269 scaffold that could be utilized in cancer treatment.
Use Of The P75NTR Extracellular Domain As A Therapeutic Target For The Treatment Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$733,633.00
Summary
AlzheimerÍs disease is the most common form of dementia and is caused by both environmental and genetic variations. With aging, a toxic peptide accumulates in the brain and causes loss of memory and cell death. This study aims to elucidate how the toxic peptide is generated and how to remove it in order to prevent and treat the disease.
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.
Characterization Of A Novel IFNbeta Signaling Axis Mediated Via IFNAR1
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
Type I interferons (IFNs) play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. This project will investigate a novel IFN signaling axis that we have recently characterized that is mediated via the low affinity IFN receptor, IFNAR1. This signaling axis occurs independently of the high affinity IFN receptor IFNAR2 and contributes to lethality in a model of septic shock.
Activation Of The Respiratory Syncytial Virus Fusion Protein
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Respiratory Syncytial Virus (RSV) is the most important viral cause of respiratory tract disease in both infants and the elderly. However, there are few available options for control, whether by vaccination or therapeutic intervention. This proposal investigates the way RSV infects cells. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can block this process and new insights for the generation of vaccine candidates.