The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determinat ....Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determination. The underpinning experimental technology, termed reverse transfection arrays, allows for high-throughput assessment of cellular phenotype properties for individual proteins.Read moreRead less
Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry ....Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry for targeted drug design, which could realise benefits in the form of novel medical treatments and reduced side effects. The monolayer template technology will also extend the capabilities of the National Cryo-EM facility, the infrastructure of which, is open for all Australian researchers. Read moreRead less
Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepress ....Determinants of Expression, Assembly and Function of the Noradrenaline Transporter. The noradrenaline transporter protein that is the focus of this project is important for mental health because it belongs to the family of proteins where psychostimulants, such as cocaine, and drugs used in the treatment of depression act. The project will lead to exciting advances in our understanding of how the structure of this protein controls its functions, and potentially to the design of better antidepressant drugs and to the design of drugs to prevent the effects of cocaine.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668526
Funder
Australian Research Council
Funding Amount
$542,000.00
Summary
Biomolecular discovery and analysis facility. This facility will provide Australian researchers with unrivalled access to advanced cell visualisation and analysis tools, which until very recently were only available to the pharmaceutical industry and large US and European institutions. The facility will allow new approaches to identifying novel natural products and understanding cell signalling pathways. Knowledge of these pathways and the identification of molecules that can affect them are key ....Biomolecular discovery and analysis facility. This facility will provide Australian researchers with unrivalled access to advanced cell visualisation and analysis tools, which until very recently were only available to the pharmaceutical industry and large US and European institutions. The facility will allow new approaches to identifying novel natural products and understanding cell signalling pathways. Knowledge of these pathways and the identification of molecules that can affect them are keys to understanding normal cellular physiology and identifying drug-like molecules able to inhibit malfunctioning pathways found in different disease such as cancer. The facility will accellerate drug discovery and basic research in cell biology and underpin National Research Priorities.Read moreRead less
High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this pr ....High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this project will allow us to develop the new method of electron microscope tomography and apply it to a crucial question in biology. This will be a vital technique for Australian investigators in the coming years and this project will allow scientists and students to be trained in these state-of-the-art techniques.Read moreRead less
Role of 3'-phosphorylated phosphoinositides in neurosecretion. Neurons communicate through the release of neurotransmitter by synaptic vesicles. Minute changes underlie normal processes such as memory and modifications of neurotransmitter level contribute to a number of neurological diseases. I am interested in deciphering the role of phosphoinositides, an inner membrane-based lipid, during steps leading to the fusion of a synaptic vesicle with the plasma membrane. I have recently discovered tha ....Role of 3'-phosphorylated phosphoinositides in neurosecretion. Neurons communicate through the release of neurotransmitter by synaptic vesicles. Minute changes underlie normal processes such as memory and modifications of neurotransmitter level contribute to a number of neurological diseases. I am interested in deciphering the role of phosphoinositides, an inner membrane-based lipid, during steps leading to the fusion of a synaptic vesicle with the plasma membrane. I have recently discovered that phosphatidylinositol-3 phosphate production was critical for the vesicle to acquire the competence to fuse with the plasma membrane. This project aim to understand by which mechanism this lipid interacts with the release machinery to promote such priming step.Read moreRead less
Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a ....Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution o ....Conotoxins: Novel probes for ion channel structure and function. Voltage-dependent and ligand-gated ion channels are intrinsic membrane proteins that play a central role in communication in excitable cells, particularly in the nervous system. The primary goals of this project are (i) to define at a molecular level, the structural and functional determinants of ion channel/conotoxin interactions and (ii) develop new probes that advance neurophysiological research. The diversity and distribution of ion channel types and subtypes being uncovered through the use of molecular biology and conotoxin probes presents an exciting opportunity for the future development of novel ion channel therapeutics.Read moreRead less
New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatmen ....New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatment for pain, as well as substantial royalty returns from drugs sales. Discoveries from the program are also likely to lead to an enhancement in Australia's reputation in the neurosciences and to the development of new diagnostic research tools. The major community benefit will be a reduction in the suffering of chronic pain patients.Read moreRead less