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
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
Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less
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
Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mit ....Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mitochondria interactions and their impact on regulating cellular lipid metabolism. The intended outcome of this project is to provide fundamental new knowledge in understanding how organelles interact and how lipid metabolism is regulated. This knowledge has applications for the primary industries and biotechnology sector.Read moreRead less
Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowle ....Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of developmental biology.
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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
The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cel ....The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cell. Thus, by use of cutting-edge fluorescence microscopy methods, the overall aim of this research project is to determine the biophysical mechanism by which the HP1a monomer to dimer transition spatially and temporally modulates live cell chromatin network organisation to ensure faithful transmission of the genome.Read moreRead less
Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular m ....Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular matrix within the hypothalamus and discover how it regulates energy homeostasis. The outcomes of this project are to provide new knowledge in understanding how the brain regulates metabolism, to promote population health & wellbeing, develop new technologies and training the next generation of researchers.Read moreRead less
Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research ....Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research is important because DNA damage threatens organism survival and this project has the potential to define how this genomic threat is resolved at the single molecule level. The benefit of this research is a fundamental insight into DNA repair biology and development of imaging technology to quantify genome function.Read moreRead less