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Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, ....Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, bias and heteromerisation. Expected outcomes also include generation of new pharmacological tools through interdisciplinary collaborative research between multiple institutions. There is significant expected economic benefit through commercialisation of new tools and facilitation of novel drug discovery.Read moreRead less
An attack from all angles! Multiphase particle systems that target respiratory infection. This project will result in advanced inhaled medicines for lung infection. Micron-particles will be engineered to have sustained drug release when deposited at sites of infection, yet avoid natural clearance and defence mechanisms. To study these systems, a series of characterisation, in vitro cell and in silico tools will be developed.
Novel pharmacological agents to target stroke-induced brain injury. There is a looming stroke epidemic in Australia. 72% of Australian stroke sufferers are over the age of 65 and whereas in 1997 only 12% of Australians were in that age group, by 2030 that number will have increased to 23%. There is an urgent need for novel therapies. This project will aid the development of a novel anti-stroke therapy.
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
Pandora's toolbox: The use of Fluorosomes to formulate nanoparticle gene therapy for respiratory diseases. This project will result in a technology for treating lung diseases. A new approach to gene therapy will be developed via packaging these bio-molecule inside a self-assembled Fluorosome structure for delivery using conventional pressurised inhalers. These systems will be investigated using state-of-the-art technologies developed during the project.
Light-responsive nanomaterials as nanomedicines: new approaches to treating macular degeneration, cancer and other critical unmet therapeutic needs. Nanotechnology is enabling new medicines for the treatment of important diseases such as cancer and macular degeneration. This project will investigate novel nanomaterials for the development of new highly effective medicines that can be controlled after administration, leading to reduced side effects and increased convenience for patients.
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
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 endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Targeting an impending global disaster: the mismatch between increasingly drug-resistant superbugs and development of new antibiotics. This project will develop much-needed novel antibiotics for treating infections caused by bacteria that are resistant to all current antibiotics. It will make a significant contribution to the global medical challenge of a shortage of new antibiotics.