Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.Read moreRead less
The rational design and construction of new genetic circuits for applications in synthetic biology. By designing, building and testing new gene control modules, this project will gain an understanding of the design principles required for the construction of biological circuits with predictable and controllable behaviour. The ability to build such circuits will have significant economic benefit in areas such as metabolic engineering and biomedicine.
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how th ....Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how the human genome is replicated. This knowledge is expected to generate research publications of high quality and provide economic benefits, such as unlocking new potentially patentable DNA technologies. Read moreRead less
Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge ....Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge into how the mitochondrial division machine assembles and how mitochondrial fate is determined.Read moreRead less
Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the cr ....Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the crosstalk between organelles and the cytoskeleton. To date, the role of microtubules remains elusive. Using interdisciplinary approaches combining advanced imaging technology with novel cell biology methods, the project aims to uncover fundamental knowledge about how cells interact with their environment.Read moreRead less
Advancing programmable genetic computation to control plant gene activity. Plants can sense diverse internal and external conditions and integrate them to appropriately tune their response and maximize fitness. Plant biotechnology relies heavily on manipulating gene activity to change cell functions and confer advantageous agronomic traits. However, our ability to control plant gene activity remains rudimentary, limiting our biotechnology capabilities. This project aims to develop synthetic gene ....Advancing programmable genetic computation to control plant gene activity. Plants can sense diverse internal and external conditions and integrate them to appropriately tune their response and maximize fitness. Plant biotechnology relies heavily on manipulating gene activity to change cell functions and confer advantageous agronomic traits. However, our ability to control plant gene activity remains rudimentary, limiting our biotechnology capabilities. This project aims to develop synthetic gene logic gates in plants, to enable the construction of programmable genetically-encoded computational functions that can sense and process customizable inputs to drive desired changes in plant function. This advance will underpin useful applications in plant biotechnology such as improved crop stress tolerance and yield.Read moreRead less
Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be use ....Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be used to construct and control purpose-built genetic networks and pathways. The results of this project are expected to add to the molecular tookit available to synthetic biologists.Read moreRead less
Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed t ....Tuning Molecular Translocaton by Close-Field Electroporation. This project aims to determine the underlying mechanisms by which DNA and other molecules are able to migrate across the cell membrane in response to highly localised electric fields. It has recently been shown that focusing of electric fields at the cellular level, using an array of small electrodes, results in unexpectedly high cell transfection efficiencies. It has been termed 'close-field electroporation'. Here it is proposed to establish the properties of the electric fields around cells and cell membrane interactions with these fields that enable molecular translocation. This fundamental science could have broad implications in the domains of drug delivery, gene therapy and neural stimulation.Read moreRead less
Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology re ....Regulation of DNA synthesis and host evasion by Lentivirus Capsids. This project aims to investigate how a type of virus, exemplified by HIV, can synthesise DNA in the cytoplasm of a host cell, without triggering the cell’s innate immunity when DNA is detected outside the nucleus. It expects to advance understanding of the role of the virus’ protein shell in regulating DNA synthesis during infection. The project outcomes should include enhanced capacity for fundamental virus and cell biology research in Australia. The project anticipates contributing to new tools for delivering genes to cells, benefiting therapeutic and biotechnology applications.Read moreRead less