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
Tissue Ferritin Acts As A Proinflammatory Mediator Of Hepatic Fibrosis In Chronic Liver Disease Via Multiple Receptors In Hepatic Stellate Cells Responsible For Both Binding And Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$777,887.00
Summary
Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology, the cells responsible for liver scarring (fibrosis) in Haemochromatosis. This proposal will identify the receptor responsible for eliciting ferritin's proinflammatory action and assess its role in fibrosis. This study will have implications in chronic liver diseases of varying aetiologies where elevated serum ferrritin is associated with inflammation.
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.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven 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