The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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Decoding miRNA regulated genetic circuits. This project will aim to develop a much better understanding of how the process of making proteins from genes is regulated, and will develop scientific software capable of predicting how a cell will respond to changes in this regulation. The results will have widespread use, including assistance in deciding the best treatments for genetic diseases.
New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of fut ....New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of future scientists, and strengthening international collaborations across academia and industry. This will contribute to a high-quality workforce for research and innovation, and secure Australia’s position at the forefront of immunology research driven by cutting-edge technologies. Read moreRead less
Understanding prokaryotic small proteins from context. Prokaryotic small proteins are increasingly recognised to play important biological roles but have been largely overlooked due to the lack of adequate tools to study them. This project aims to develop new methods to identify and predict the functions of small proteins from microbial communities by studying sequence patterns in their genomes. These predicted functions will be confirmed in the laboratory, leading to a catalogue of newly charac ....Understanding prokaryotic small proteins from context. Prokaryotic small proteins are increasingly recognised to play important biological roles but have been largely overlooked due to the lack of adequate tools to study them. This project aims to develop new methods to identify and predict the functions of small proteins from microbial communities by studying sequence patterns in their genomes. These predicted functions will be confirmed in the laboratory, leading to a catalogue of newly characterised small proteins from a diverse range of habitats and geographies. By creating new ways to study the role of small proteins in the global microbiome, we will provide the foundational knowledge required to leverage these proteins for use in biotechnology. Read moreRead less
Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundament ....Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundamental insights into how SIK3 in the hypothalamic neurons regulates energy homeostasis. Benefits include improving population health and wellbeing, informing the development of new bio-medical technologies, and expanding the capabilities of Australia’s next generation of researchers.
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Developing a new class of RNA delivery vehicle using synthetic virology. This project aims to develop robust protein cages derived from the empty shells of viruses, or capsids, to protect and deliver sensitive cargo such as RNA in agricultural settings. It will do so by directed evolution of non-infectious capsids in the lab. This will uncover the molecular mechanisms underpinning the response of viruses to chemical and biological signals and create a new class of RNA delivery vehicle. This synt ....Developing a new class of RNA delivery vehicle using synthetic virology. This project aims to develop robust protein cages derived from the empty shells of viruses, or capsids, to protect and deliver sensitive cargo such as RNA in agricultural settings. It will do so by directed evolution of non-infectious capsids in the lab. This will uncover the molecular mechanisms underpinning the response of viruses to chemical and biological signals and create a new class of RNA delivery vehicle. This synthetic biology approach combines virology and protein engineering to establish a platform biotechnology for stable and effective delivery. The project expects to demonstrate the potential of nature’s nanoparticles, virus capsids, to enhance the efficacy of RNA technologies in a wide range of applications.Read moreRead less
Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology ....Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology platform in which to engineer small molecules and probiotics to improve mitochondrial health and enhance fitness in a range of animals. This should provide significant benefits, through both scientifically relevant outcomes and economic benefits through technological advancements.Read moreRead less
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.Read moreRead less
Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected ....Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected to unravel general principles of nucleotide-based signalling, and the expected outcomes will include new molecular mechanisms relevant to cell-death and pathogen defence in mammalian and bacterial systems, which should provide significant benefit for a range of applications in human biology and biotechnology.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