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.
Computational And Structural Studies Of Protein-GPCR Interactions Underlying HIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
While it is known that HIV entry and disease progression relies upon the interaction of a number of distinct proteins, the precise nature of these interactions remains unclear. The purpose of this fellowship is apply computational and experimental techniques to stabilise members of the protein complex so that we can understand their structure.
Analysis Of Calcitonin Receptor Binding And Function
Funder
National Health and Medical Research Council
Funding Amount
$382,821.00
Summary
Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small prote ....Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small protein molecules that cirulate through the body. One such circulating molecule is calcitonin, a peptide that plays an important role in maintaining circulating calcium levels in the body, which is essential for proper maintenance of the skeleton. As a consequence of this action, calcitonin is an important clinically used tool in the treatment of bone disease such as osteoporosis and Paget's disease. Due to the molecular nature of calcitonin and its receptors (and other related receptors) that have a broad, complex mechanism of interaction, we have very little definitive information on how calcitonin interfaces with its receptor to signal to target cells. The current project utilises a novel method of permanently linking calcitonin to its receptor, allowing identification of how the two components come together. Furthermore, the project will explore the functional consequence of naturally occuring genetic variation (genotype) and also examine whether the occurence of specific calcitonin receptor genotype is correlated with disease markers for osteoporosis and obesity. This information provides important fundamentals for understanding how this and related receptors work and the potential for rational design of improved theraupeutic tools.Read moreRead less
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
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.
Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.