Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it i ....Bias and allostery at the calcium sensing receptor. This project aims to provide a mechanistic and dynamic picture of the structure, function and physiology of the human calcium sensing receptor (CaSR), which is critical for vertebrate life. By responding to chemicals in the body, it acts as a universal nutrient sensor to maintain extracellular calcium homeostasis and mediate biological functions, including neurotransmission, inflammation, digestion, blood pressure and development. However, it is not known how this single receptor controls the actions of multiple ligands to mediate numerous functions. By elucidating the roles of the CaSR and its ligands, this project aims to better understand fundamental physiological processes.Read moreRead less
Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is acti ....Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is activated responding to different ligands. The anticipated outcome including an enhanced capacity for understanding the fundamental biology, a stronger national and international collaborations. This will provide significant benefits including expanded basic knowledge and improvements in drug development efficiency. 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
Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
Oxytocin receptor PET ligands: imaging the love receptor’s engagement. This project aims to develop a positron emission tomography (PET) ligand for the oxytocin receptor. This novel platform is significant as it will allow the scientific community to answer questions about the role of the oxytocin receptor in the important process of social behaviour which underlies quality of life. This knowledge gap has remained unanswered for decades due to the lack of specific techniques to measure oxytocin ....Oxytocin receptor PET ligands: imaging the love receptor’s engagement. This project aims to develop a positron emission tomography (PET) ligand for the oxytocin receptor. This novel platform is significant as it will allow the scientific community to answer questions about the role of the oxytocin receptor in the important process of social behaviour which underlies quality of life. This knowledge gap has remained unanswered for decades due to the lack of specific techniques to measure oxytocin receptor engagement. It is also significant as it will equip Australian startup Kinoxis Therapeutics to progress their molecules to market, a process enabled by measuring oxytocin receptor engagement. Our dual expertise on the oxytocin receptor and PET ligand development uniquely situate us to generate this technology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100356
Funder
Australian Research Council
Funding Amount
$450,241.00
Summary
Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and ....Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and biophysical approaches. Novel knowledge will be generated to improve our understanding on how bacteria remodel their outer membrane in response to environmental stress. This will benefit the future design of much-needed antimicrobial strategies including products and technologies to target bacterial membrane. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210100422
Funder
Australian Research Council
Funding Amount
$447,346.00
Summary
Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this pro ....Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this project include the development of new venom-based research tools and improved techniques for studying sodium channel function. This will provide significant benefits, including advancement of fundamental knowledge in physiology and the development of novel analgesics. Read moreRead less
How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes could pro ....How lipid binding proteins shape the activity of nuclear hormone receptors. This project aims to explore how a family of lipid binding proteins control organ specific activation of nuclear receptors – receptors that play a key role in generating energy and are critical for life. The project will employ chemical, molecular, cell biology approaches to generate new knowledge about lipid binding protein-receptor interactions and how these complexes dictate receptor activation. The outcomes could provide a roadmap to design drugs that interact with the right protein in the right tissue and in doing so dramatically enhance drug specificity. This will benefit the success of drug treatments which require stimulation of a therapeutic response at a target site, and avoidance of potentially toxic activity at other locations.Read moreRead less
Understanding and controlling neuropeptide GPCR-transducer coupling. G protein-coupled receptors (GPCRs) are physiologically essential, yet the spatiotemporal complexity of receptor function has limited our understanding of their function and success in drug development. Using a multi-disciplinary approach integrating GPCR signalling, trafficking and drug delivery, this research program aims to understand, and control, the molecular mechanisms that enable a single receptor to respond to differen ....Understanding and controlling neuropeptide GPCR-transducer coupling. G protein-coupled receptors (GPCRs) are physiologically essential, yet the spatiotemporal complexity of receptor function has limited our understanding of their function and success in drug development. Using a multi-disciplinary approach integrating GPCR signalling, trafficking and drug delivery, this research program aims to understand, and control, the molecular mechanisms that enable a single receptor to respond to different ligands to promote unique cellular processes. The anticipated outcomes include an enhanced capacity for understanding fundamental biology, and stronger national and international collaborations. It will provide significant benefits including expanded basic knowledge and advancement of drug delivery technology.Read moreRead less