Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347955
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first ....A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first cell-sorting facility dedicated to the production of nerve cells suitable for molecular characterization and screening, providing the basis for identifying key molecules regulating brain function, ageing and repair of great importance to the biotechnology/pharmaceutical industry.Read moreRead less
Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also disco ....Signalling cross-talk through Suppressors Of Cytokine Signalling (SOCS) initiates luteolysis in the ovary. Members of the newly discovered SOCS protein family block cytokine signal transduction pathways, including those for prolactin and GH. We have discovered that one of these proteins, SOCS-3, is upregulated in the corpus luteum of the ovary by prostaglandins and propose that induction of prolactin or GH resistance is a hitherto unrecognised and critical step in luteolysis. We have also discovered that this cross-talk between prostaglandin- and cytokine-receptor signalling pathways occurs in preadipocyte and breast cell lines and propose that this research will serve as a paradigm for understanding how sensitivity to cytokines can be controlled at a molecular level.Read moreRead less
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
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
The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
The protein import machinery of peroxisomes. The peroxisome is a subcellular organelle essential for cellular metabolism. Our understanding of the formation, or biogenesis, of the peroxisome has advanced to the stage where many of the proteins involved in this process have been identified. What is less clear is how these proteins interact to form functional macromolecular complexes in the cell. In this project we will use biochemical approaches to isolate protein complexes involved in peroxisome ....The protein import machinery of peroxisomes. The peroxisome is a subcellular organelle essential for cellular metabolism. Our understanding of the formation, or biogenesis, of the peroxisome has advanced to the stage where many of the proteins involved in this process have been identified. What is less clear is how these proteins interact to form functional macromolecular complexes in the cell. In this project we will use biochemical approaches to isolate protein complexes involved in peroxisome biogenesis. These studies will help to elucidate the molecular mechanisms of peroxisome biogenesis and contribute to an understanding of organelle biogenesis generally.Read moreRead less
The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the- ....The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the-art structural and molecular cell biology research. By addressing an area of great interest internationally the project will have the capacity to increase Australia's knowledge base and strengthen it's reputation for research excellence.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