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Discovery Early Career Researcher Award - Grant ID: DE150101777
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the ....Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the project aims to study how the proteins and RNA are packaged into exosomes. Membrane molecules that are detected only in the exosomes may have important signalling implications and may aid in the uptake/fusion of exosomes by/with target cells. The project aims to improve our understanding on signalling mediated by exosomes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100524
Funder
Australian Research Council
Funding Amount
$365,057.00
Summary
Manipulating selected inflammatory responses in macrophages. This project aims to define the structural and functional interactions of a new transmembrane adaptor SCIMP. SCIMP has recently been shown to effect the inflammatory pathway. The project outcomes will include the first structure of this unconventional complex. The project will have significant flow on benefits including new knowledge and new protein methodologies for end-users in research and industry, and ultimately economic impact.
Discovery Early Career Researcher Award - Grant ID: DE150101648
Funder
Australian Research Council
Funding Amount
$363,000.00
Summary
A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised gro ....A novel mechanism for the control of growth factor activity. Growth factors are secreted signalling molecules that govern fundamental biological processes such as cell growth, proliferation and death. The mechanism for growth factor control by a Membrane Attack Complex/Perforin-like (MACPF) protein is highly novel as MACPF proteins typically function to kill pathogens during the vertebrate immune response. This project aims to reveal how the MACPF protein Torso-like controls highly localised growth factor signalling, using the sophisticated genetic and advanced imaging methods possible in the fruit fly Drosophila. This project aims to understand growth factor control as its deregulation leads to serious developmental disorders and diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100575
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to ....Pathogen detection in mammals. This project aims to study the role of a host molecule in immune protection. Multicellular organisms need to recognise pathogens to initiate immune protection. To do this, pathogen-specific molecules are presented to the immune system causing activation. Recently a mode of pathogen recognition was discovered in mammals. As microbes synthesise essential vitamins, they release tell-tale metabolite by-products, which a host molecule called MR1 captures and presents to white blood cells. However, it is not understood how MR1 accomplishes this, the cellular machinery required, or how the metabolites are guided to MR1. Understanding this process is expected to explain microbial pathogen recognition.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100546
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Activity-dependent regulation of glutamate receptor trafficking in neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are not well understood. This project will use structural, biochemical, molecular and cell biological assays to study the molecular processes that control glutamate receptor trafficking in the ....Activity-dependent regulation of glutamate receptor trafficking in neurons. This proposal aims to understand the molecular mechanisms of neuronal communication and how neurons modify their synaptic strength. Although these processes are essential for normal brain function, the precise underlying mechanisms are not well understood. This project will use structural, biochemical, molecular and cell biological assays to study the molecular processes that control glutamate receptor trafficking in the postsynaptic compartment. It will elucidate how neural plasticity is generated and maintained, information critical for understanding sensory processing, learning and memory throughout life. The findings could identify cellular targets for interventions to enhance cognitive performance and maintain optimal brain function.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102321
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Exploiting pathogen-host interactions to dissect the mammalian endocytic pathway. Salmonella manipulates the cells of the human body to cause disease. Understanding the molecular machinery that controls this process will provide profound insight into how the bacteria orchestrates this manipulation as well as provide possible avenues for intervention and even cures for diseases like typhoid fever.
Discovery Early Career Researcher Award - Grant ID: DE230101128
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new ....Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new understanding of proprioception and motion sensing. The new multimodality approach generated in this project is expected to evolve as a national facility for neuro-mechanobiology, and future research may lead to the inspiration of novel bionic sensor design and brain-computer interface for future neuroengineering industry.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101681
Funder
Australian Research Council
Funding Amount
$457,139.00
Summary
Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a br ....Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a broad range of pharmacological tools to facilitate isolation of distinct functional states. The knowledge gained from these studies will advance fundamental understanding of physiologically important receptor activation and efficacy, while the approaches developed will enable similar investigation of other receptor classes.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101035
Funder
Australian Research Council
Funding Amount
$369,500.00
Summary
Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not under ....Ion regulation in Apicomplexan parasites. This project aims to determine how Apicomplexan parasites regulate their sodium and chloride levels to support the development of new parasite control measures. Apicomplexan parasites cause devastating animal and human diseases. Little is known about the physiology of these parasites, and options for controlling them are few. Apicomplexan parasites must precisely control their internal ion compositions in order to survive, but how they do so is not understood. Recent work has identified a unique Apicomplexan sodium transporter and revealed a number of chloride transporter candidates. Using a combination of molecular biology and physiological techniques, this project aims to characterise the Apicomplexan sodium transporter in detail and elucidate the molecular mechanisms of chloride transport.Read moreRead less