Subunit stoichiometry and arrangement in the glycine receptor. Glycine receptors are important for nervous system function. These receptors comprise a mixture of 5 alpha and beta subunits arranged around a central ion-conducting pore. The subunit stoichiometry (i.e., numbers of alpha and beta subunits) and arrangement (i.e., subunit order) are unknown. The first aim of this project is to define these parameters using tethered subunits. The second aim is to use the tethered subunits to probe th ....Subunit stoichiometry and arrangement in the glycine receptor. Glycine receptors are important for nervous system function. These receptors comprise a mixture of 5 alpha and beta subunits arranged around a central ion-conducting pore. The subunit stoichiometry (i.e., numbers of alpha and beta subunits) and arrangement (i.e., subunit order) are unknown. The first aim of this project is to define these parameters using tethered subunits. The second aim is to use the tethered subunits to probe the structure and function of glycine and zinc binding sites at an unprecedented level of resolution. The results will provide crucial new information concerning glycine receptor structure and function.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0236372
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and p ....CENTRIFUGATION FACILITIES FOR THE GENETICS ANALYSIS FACILITY. Access to both a high-speed centrifuge and an ultracentrifuge is essential for a wide range of biochemistry and molecular biology research projects. A high-speed centrifuge is essential for the collection of bacteria cultured to express specific proteins as well as the collection of purified proteins isolated from a wide range of organisms. Similarly an ultracentrifuge is required for the isolation of viruses and the preparation and purification of RNA and DNA. The two machines will facilitate the continuation of research projects funded by both government and industry grants. The centrifuges will complement the equipment available in the Genetic Analysis Facility.Read moreRead less
Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary g ....Conantokin selectivity for heteromeric N-methyl-D-aspartate (NMDA) receptors. NMDA receptors are ligand gated ion channels formed by heterogeneous population of subunits with distinct pharmacological and biophysical properties. The heterogeneic receptors are differentially expressed during development and play an important role in many physiological and pathological processes. Conantokins are toxins isolated from Conus venoms, which target NMDA receptor subunits with high affinity. The primary goal of this study is to examine the effects of conantokins on the molecular properties of different NMDA receptor subtypes in vivo and in vitro.Read moreRead less
A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endop ....A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endopolyploidy with age, and show unpredictable or patchy silencing. We speculate that differential silencing is a natural control mechanism in the exploitation of polyploidy in plants. The sugarcane system provides an exceptional opportunity to identify the sequences that trigger and protect from silencing, and to develop approaches to avoid the problem.Read moreRead less
Efficient organelle transformation. Chloroplasts and mitochondria are the powerhouses of plant and animal cells. Ability to express introduced genes in these organelles has enormous biotechnological potential in agriculture and medicine, but practical development has been almost stalled for 15 years by very low transformation efficiency. Plastid transformation is today routine only in tobacco; and mitochondrial transformation has been achieved only in yeasts and algae. We have developed a soluti ....Efficient organelle transformation. Chloroplasts and mitochondria are the powerhouses of plant and animal cells. Ability to express introduced genes in these organelles has enormous biotechnological potential in agriculture and medicine, but practical development has been almost stalled for 15 years by very low transformation efficiency. Plastid transformation is today routine only in tobacco; and mitochondrial transformation has been achieved only in yeasts and algae. We have developed a solution, and achieved the key technical requirements for proof of concept. This collaboration between industry, government and university partners will deliver key Australian-owned IP, for environmentally-friendly plant biofactories, and for treatment of mitochondrial genetic disorders.Read moreRead less
Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms cont ....Myofibroblast differentiation: from haemopoietic cells to smooth muscle. Until very recently the ability of adult cells with specific differentiated functions to re-differentiate for another function was thought to be extremely limited. However we have shown that cells ultimately derived from the bone marrow can differentiate into fibroblasts, then into myofibroblasts and then into smooth muscle cells. This project will build on these unique findings and determine the molecular mechanisms controlling this process. We hypothesise that the local environment of a cell is critical and will involve a combination of particular extracellular matrix and growth factors as well as mechanical tension and the presence of other cell types.Read moreRead less
CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research wil ....CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research will provide new data on the fundamental cellular and molecular events that are required to trigger the birth, differentiation and conditions for growth of new neurons in the adult nervous system. The generation of such insights will be critical for any translational research.
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Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of ....Understanding how the multiple roles of olfactory ensheathing cells guide the growth and regeneration of olfactory axons. The outcomes of this project will increase the understanding of how nerve cells develop and regenerate after injury. The research outcomes and the development of new innovative methodologies as part of the project will be of high significance for the neuroscience research community both within Australia and overseas. The findings will also pave the way for the development of novel therapies that promote neuronal regeneration relevant for disorders such as spinal cord injury and Alzheimer's disease, which constitute a large socio-economic burden in Australia. Currently, 400 people contract spinal cord injury every year, corresponding to an annual cost of $1 billion, and more than 500 000 aging people suffer from Alzheimer's disease.Read moreRead less
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less