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Discovery Early Career Researcher Award - Grant ID: DE170100152
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Molecular insight into allosteric modulation of G protein-coupled receptors. The project aims to understand the molecular mechanisms underlying signal transduction and allosteric modulation of G protein-coupled receptors (GPCRs). Allosteric modulation of proteins is a fundamental process where two distinctly different binding sites are linked through a conformational change. This project will use structural biology, medicinal chemistry and analytical pharmacology to investigate how chemical prob ....Molecular insight into allosteric modulation of G protein-coupled receptors. The project aims to understand the molecular mechanisms underlying signal transduction and allosteric modulation of G protein-coupled receptors (GPCRs). Allosteric modulation of proteins is a fundamental process where two distinctly different binding sites are linked through a conformational change. This project will use structural biology, medicinal chemistry and analytical pharmacology to investigate how chemical probes modulate GPCRs at an atomic level, and understand the mechanisms underlying signal transduction. Project outcomes are intended to advance membrane protein crystallography and GPCR biology, and benefit the pharmaceutical industry.Read moreRead less
Understanding the changes in brain chemistry associated with schizophrenia. Current drugs for schizophrenia only work in 30% of patients. To develop better therapies, we must understand the changes in the brains of people with the disorder. This research will explore a chemical system in the brain that is changed in schizophrenia and begin to investigate whether counteracting these changes are therapeutically beneficial.
Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project ....Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project outcomes are intended to lead to significant advances in membrane protein structure determination and will have a substantial impact on future research in the pharmaceutical industry.Read moreRead less
Biosynthesis, folding and modification of conotoxins. Disulfide-rich peptides represent a diverse family of bioactive molecules which have been developed as drugs for the treatment of severe pain. This project seeks to understand their biosynthesis and how their functional diversity is generated. Such information will assist the translation of more of these novel peptides into new drugs.
Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100008
Funder
Australian Research Council
Funding Amount
$347,500.00
Summary
Super Resolution Confocal Microscopy Facility. Super resolution confocal microscopy facility:
This project aims to establish a super-resolution confocal microscopy facility with unrivalled resolution, sensitivity and speed. The widespread application of super-resolution microscopy has so far been limited because of the special sample preparation and technical skills required. The project aims to provide us with the ability to image thicker samples, such as animal and plant tissue, without these ....Super Resolution Confocal Microscopy Facility. Super resolution confocal microscopy facility:
This project aims to establish a super-resolution confocal microscopy facility with unrivalled resolution, sensitivity and speed. The widespread application of super-resolution microscopy has so far been limited because of the special sample preparation and technical skills required. The project aims to provide us with the ability to image thicker samples, such as animal and plant tissue, without these limitations. This would enable us to capture three-dimensional data at both the cellular and tissue level, providing researchers with a level of detail never before seen. The facility may create new knowledge in life science, including visual neuroscience, developmental neurobiology, plant growth, stem cell regeneration, the role of trace metals in physiology, and vaccine and drug development.Read moreRead less
The role of P2X7 and P2X4 receptor mediated innate phagocytosis in pathogenesis and treatment of neurodegenerative diseases. This project will identify how inherited variation in two proteins of the brain can accelerate the removal of neurones and predispose to a range of neurodegenerative diseases. Knowledge of the biological basis of this finding will allow a search for new compounds which will slow and protect against this form of neurodegeneration.
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.Read moreRead less
Resolving the Structures of Human Muscarinic M1 and M4 Receptors. Muscarinic receptors are vital for most basic human brain functions. These receptors are changed in schizophrenia and Alzheimer's disease. This project will determine the structure and localisation of two of these receptors in order to i) understand their roles in brain disorders and ii) develop drugs to treat disorders involving them.
Regulation of neurite outgrowth by an inhibitor of PI3K signalling. PIPP is an enzyme which inhibits important cellular functions such as cell maturation. We have shown the amount of PIPP is increased in Alzheimer's disease brains. This project will characterise the mechanisms by which PIPP regulates brain cell function to identify how PIPP may be acting to exacerbate Alzheimer's disease development/progression.