Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pa ....Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pathogen and mitochondrial biology and advanced cell biology tools. With most of the effector proteins yet to be characterised, benefits from the project will be to reveal specifically how these target mitochondria, and more broadly, how bacterial pathogens manipulate organelles for their survival.Read moreRead less
Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins orga ....Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins organises in space and time to regulate synaptic connectivity. This will provide significant benefits, including molecular-level insight into the inner workings of the brain and interdisciplinary training for students. The expected outcomes include a deeper understanding of brain functions, such as learning and memory.Read moreRead less
Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate recep ....Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate receptors is regulated in neurons during plasticity and learning. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of the cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100700
Funder
Australian Research Council
Funding Amount
$429,449.00
Summary
A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools fo ....A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools for molecular machine discovery and identification of ways to adapt molecular machines for biotechnological applications. This work should enhance Australia-UK ties through collaboration, provide benefits toward nanobiotechnology and economic benefits through more efficient food production.Read moreRead less
Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and ....Mapping the integration of T cell fate control across time and space. This project aims to apply new methods to determine how coordination of signalling complexes impacts upon the fate of cells of the adaptive immune system. It expects to determine how the context of signallng orchestrates cell fates such as differentiation, death and proliferation. The project is expected to yield an experimental and analytical platform for further investigations into a broad range of biological questions, and to provide new knowledge of this fundamental problem. This platform should support further work that ultimately provides new models for tissue and immune cell regeneration, and new manufacturing platforms for therapies for humans and livestock, among other benefits.Read moreRead less
Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesi ....Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesion. Despite advances in the understanding of Commander function, little is known about how Commander is assembled and interacts with other essential proteins. This project will use multidisciplinary cellular and structural biology approaches to reveal the architecture of Commander at an atomic level.Read moreRead less
The functional architecture of a unique family of lipid droplet proteins. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will ....The functional architecture of a unique family of lipid droplet proteins. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease. Read moreRead less
Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin a ....Chemical staples and chemical probes to dissect dynamins cellular roles. Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin activity. It is known that Dynamin helices and rings are believed responsible for at least three in cell biological functions: in hormone, neutral and receptor internalisation; cellular mitosis and in actin dynamics. Prior to this work we have lacked the tools to understand the role of shape modulation of protein function.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100707
Funder
Australian Research Council
Funding Amount
$450,926.00
Summary
Towards a molecular fingerprint for human-specific endogenous retroviruses. This project aims to understand how ancient viral sequences resident in the human genome can contribute to cellular processes. Using a novel molecular toolbox that combines affinity-directed proximity labelling mass spectrometry and single molecule microscopy, this project will characterise the cellular fingerprint of a human endogenous retrovirus family HERV-K (HML-2). This fingerprint will comprehensively describe how ....Towards a molecular fingerprint for human-specific endogenous retroviruses. This project aims to understand how ancient viral sequences resident in the human genome can contribute to cellular processes. Using a novel molecular toolbox that combines affinity-directed proximity labelling mass spectrometry and single molecule microscopy, this project will characterise the cellular fingerprint of a human endogenous retrovirus family HERV-K (HML-2). This fingerprint will comprehensively describe how expressed HERV-K loci engage with the homeostasis network in human cells. This will provide significant benefits in the form of new knowledge concerning fundamental aspects of cellular homeostasis, and a state-of-the-art molecular biology toolbox ready to explore quantitatively the role of HERV-K in human health and disease.Read moreRead less