Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during developmen ....Interactions between phenome and genome at developing CNS synapses during synaptic refinement. Activity-dependent changes in synaptic transmission are vital to development and function of central neuronal networks. However, the critical factors regulating developmental changes in synaptic signals remain largely unknown. We will correlate functional changes in synaptic responses at glutamate-releasing synapses with changes in glutamate receptor composition at a critical period during development, test whether synaptic activation of receptors is required for these changes and define the pattern of activity-dependent changes in gene expression necessary for developmental changes in synaptic transmission. Understanding this interaction between synaptic phenome and activity-dependent genomic expression will expand our understanding of brain development and function.Read moreRead less
Development of novel reagents that specifically counteract EphA4 to enhance axonal regeneration. This project will examine the role of EphA4, an important guidance protein, in neural cell regeneration. The goal is to understand the signalling mechanisms that inhibit regeneration in the central nervous system and to develop novel biological agents to overcome these processes and promote functional recovery after nervous system injury or disease.
Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investiga ....Investigating the Molecular Mechanism of Synaptic Transmission. This project aims to increase our understanding of the synaptic function of the nervous system. Neurons communicate with each other via the release of neurotransmitters at specialised structures known as synapses. Synaptic vesicle (SV) release from the presynaptic neuron is essential for this neuronal transmission, which drives all aspects of nervous system function, including behaviour and cognition. This project plans to investigate how key synaptic proteins and the interactions between them regulate spontaneous SV release. It aims to reveal the molecular mechanism of both basal level regulation and the potentiation of spontaneous SV release, using a Caenorhabditis elegans model system.Read moreRead less
Transcriptional control of neural stem cell differentiation during development and disease. Understanding the molecular mechanisms that control how neural stem cells differentiate is critical to provide potential therapeutic treatment for neurodegenerative diseases and for brain cancer. This project will aim to discover, using an animal model system, the genes and molecules regulating these key biological processes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100074
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genet ....Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genetic and acquired disorders across the life-span. Remote viewing and analysis capabilities will help overcome the 'tyranny of distance', increasing national access to the facility. Repositories of digitised images will increase the availability of valuable research material to other Australian and international researchers.Read moreRead less
Dendritic information processing during sensory-motor behaviour. The neocortex is centrally involved in the control of animal behaviour. It is largely unknown how neocortical neurons contribute to the neuronal computations that generate behaviour. The project will study how individual neurons in the neocortex compute the sensory and motor signals that underlie an important exploratory behaviour in rodents.
Role Of Hepatic Stellate Cell And Liver Progenitor Cell Interactions In The Regulation Of Wound Healing And Liver Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
The liver has a remarkable capacity for regeneration following acute and chronic liver injury, however, the mechanisms which facilitate this wound healing are not understood. This project will examine the interactions between different liver cell populations, including hepatic stellate cells (liver fibroblasts) and liver progenitor cells (stem cells of the liver) and will determine which factors regulate inflammation, liver scarring and restitution of liver mass following chronic liver injury.
Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on d ....Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on defining the molecular mechanisms that regulate Arp2/3 and actin assembly in cadherin-based adhesion. Our work combines molecular characterization of regulatory mechanisms and proteomic searches for new regulators, with tests of the higher-order function of this novel process in cell adhesion and recognition.Read moreRead less
Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly qui ....Molecular control of adult neural stem cell quiescence. The objective of this project is to improve our understanding of adult neural stem cell biology and function. Within the central nervous system of the brain, neural stem cells persist throughout adult life. These cells continually produce new neurons that are pivotal for processes including learning and memory, and deficits in adult neurogenesis have been linked to age-related cognitive decline. Adult neural stem cells are predominantly quiescent, dividing rarely to ensure that they are not prematurely exhausted. However, the factors that maintain this quiescence are very poorly defined. The project aims to understand how stem cell quiescence is controlled at both a molecular and cellular level in vivo within the adult mouse brain.Read moreRead less