A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Determining the role of neuronal nicotinic acetylcholine receptor subunits in the development of addictive behaviours. The economic and health burden of substance abuse in Australia exceeds $31.5 billion and there are currently few treatment options. Nicotinic receptors (nAChRs) are a common target for the interaction of alcohol and nicotine in the brain. This project aims to determine the role of nAChRs in the development of addiction to alcohol and nicotine.
The molecular basis of ionic selectivity in nicotinic-type ion channel receptors. The ability of cell membranes to transport sodium, potassium and chloride selectively is important for many physiological processes. By elucidating the mechanisms by which membrane ion channels flux chloride ions, selectively this project will have wide-ranging ramifications from understanding physiological processes to nanofluidic device design.
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.
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
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.
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.
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.