Role of suppressor of cytokine signalling proteins (SOCS3) in defective muscle repair and ageing. Old muscles are slower and weaker than young muscles, they are injured more easily and they repair less successfully. This proposal investigates the role of SOCS3-signalling in muscle repair, ultimately to improve healing and to promote healthy ageing that will enable older Australians to enjoy a better quality of life.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100046
Funder
Australian Research Council
Funding Amount
$289,381.00
Summary
A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolut ....A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolution. The benefit of this technology is that it will enable scientists in Australia to image, for the first time, the biophysical mechanism by which a protein navigates intracellular architecture to regulate a complex biological function at the single molecule level.Read moreRead less
Systems modelling of the cardiac fibroblast. The cardiac fibroblast is a specialised cell in the heart. New evidence shows that this cell type is central to heart function, but relatively little is known about how and why. This project will develop mathematical modelling to characterise how the cardiac fibroblast regulates the functioning of the adult heart.
Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment ....Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment (the cell nucleus).Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101268
Funder
Australian Research Council
Funding Amount
$386,820.00
Summary
Stochastic mathematical modelling of the Wnt signalling pathway. The Wnt signalling pathway is pivotal in multicellular organisms, regulating cellular processes such as proliferation, apoptosis and migration. Faulty Wnt signalling is associated with degenerative diseases, developmental disorders and cancers and is therefore a potential target for therapeutic drugs. This project will perform a stochastic spatial simulation of the Wnt signalling pathway which will be matched to experimental data. ....Stochastic mathematical modelling of the Wnt signalling pathway. The Wnt signalling pathway is pivotal in multicellular organisms, regulating cellular processes such as proliferation, apoptosis and migration. Faulty Wnt signalling is associated with degenerative diseases, developmental disorders and cancers and is therefore a potential target for therapeutic drugs. This project will perform a stochastic spatial simulation of the Wnt signalling pathway which will be matched to experimental data. The model will be extended to integrate with the cell cycle. Increased proliferation in tumours has been linked to mutations in Wnt components. Using the extended model, the effect of Wnt-targeting therapeutic cancer drugs on cancer cell proliferation rates will be predicted and compared to experiments.Read moreRead less
Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance ....Systems-level characterization of scaffold protein signalling networks. The PEAK family of cell signalling scaffolds regulate cellular responses critical for normal development and physiology. This project will adopt a ‘holistic’ approach to characterizing their mechanism and function, integrating experimental and mathematical approaches and developing predictive computational models. It aims to generate fundamental new knowledge in cell, computational and synthetic biology with broad relevance that will foster establishment of new international linkages. This research will also identify strategies for engineering novel scaffolds that re-program cellular behaviour towards specific, applied outcomes, with potential benefit for the fields of synthetic biology, bioengineering and biotechnology.Read moreRead less
Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a h ....Defining the molecular switches that govern discrete cellular fates. This project aims to elucidate how mammalian cells exploit the same molecular machinery to perform completely distinct jobs. While the repurposing of proteins by cells seems widespread, the mechanisms by which this occurs remains largely undefined. The project expects to generate new knowledge in the areas of cell signalling and systems biology, with important implications for many multi-functional proteins. It will utilise a highly innovative and interdisciplinary approach that tightly integrates mathematical modelling and biological experiments. The expected outcomes will aid strategies for reprogramming cells towards a desired phenotype, which will bring significant benefits to the fields of synthetic biology and bioengineering.Read moreRead less
How protein tyrosine phosphatases select their substrates. Protein tyrosine phosphatases (PTPs) are enzymes that control the response of cells to divergent environmental stimuli. This project will determine how individual PTPs exert selective effects on cellular communication networks to coordinate organismal development, growth and survival.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less