The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
Deciphering the cellular defences against aggregating proteins in human disease. Cells have inbuilt defences for coping with proteins that bend into abnormal sticky shapes that form toxic clusters. In many diseases, including Huntington's, the clusters severely damage nerve cells. This project will identify the genes and mechanisms cells use to protect themselves from toxic clusters, which could provide new therapeutic targets.
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
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
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
Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This p ....Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels. Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This project aims to determine the basis of ion permeation and selectivity in the channels and explain the mechanisms of action for a number of common drugs. This will provide a foundation for future drug development to target specific channels for improved treatment of epilepsy, chronic pain and arrythmias. Read moreRead less
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.
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.
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