Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cel ....Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cellular processes. The outcomes will include fundamental new knowledge in cell biology and lead to the development of unique biological models that can be used to understand disease.Read moreRead less
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.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
Characterisation of p14ARF intracellular trafficking pathways. Over 3500 new cases of melanoma are diagnosed in NSW each year, and one of the most important proteins involved in suppressing melanoma initiation or growth is p14ARF. This project will characterise the movement and functions of this protein with the aim of identifying novel targets for more effective drug therapies.
Role of endocytic mechanisms in mammalian cytokinesis. Cell division requires endocytic proteins and failed cell division can contribute to cancer. This project aims to understand how endocytic proteins function to complete cell division successfully and has implications for the development of chemotherapeutic agents to treat cancer.
Assembly and stability of human voltage-gated potassium channels. The Kv11.1 voltage-gated potassium channel is an important regulator of cardiac function and a problem for the pharmaceutical industry due to its promiscuity with respect to drug binding. This project aims to investigate how Kv11.1 channels fold and assemble into tetramers and what stabilizes them in the cell membrane. Borrowing from insights gained from the structural analysis of G-Protein coupled receptors, the project intends t ....Assembly and stability of human voltage-gated potassium channels. The Kv11.1 voltage-gated potassium channel is an important regulator of cardiac function and a problem for the pharmaceutical industry due to its promiscuity with respect to drug binding. This project aims to investigate how Kv11.1 channels fold and assemble into tetramers and what stabilizes them in the cell membrane. Borrowing from insights gained from the structural analysis of G-Protein coupled receptors, the project intends to apply a novel protein stabilization strategy to facilitate the structural analysis of Kv11.1 channels. The successful completion of the project could reveal important insights into how these molecular machines work as well as enable atomic level studies of how drugs interact and bind to these channels.Read moreRead less
Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that cl ....Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that clears dangerous misfolded proteins from body fluids. Using cutting-edge approaches and a novel animal model, the project aims to establish how this system works. The outcomes are expected to improve understanding of the molecular processes affecting human ageing and disease and strengthen the framework needed to develop better strategies to combat these.Read moreRead less
The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in researc ....The fate of single virus particles during infection. This project applies innovative imaging techniques to elucidate the logistics of cellular function. Establishing a cutting-edge technology platform will spawn discovery and research creativity in fundamental science, as well as applications in biomedical and biotechnology research disciplines. We will foster a highly skilled workforce, an essential asset for maintaining and enhancing Australia's reputation and capability as a leader in research excellence.Read moreRead less
Molecular microscopy: protein and membrane dynamics in resting and activated T cells. The aim of this research, to understand the molecular organization and dynamics of the plasma membrane that underlie the signal transduction events, is at the very heart of understanding cell communication. T cell recognition and activation initiates an adaptive immune response to invading pathogens and structurally altered proteins that can be found in cancers. By providing functional insights into the molecul ....Molecular microscopy: protein and membrane dynamics in resting and activated T cells. The aim of this research, to understand the molecular organization and dynamics of the plasma membrane that underlie the signal transduction events, is at the very heart of understanding cell communication. T cell recognition and activation initiates an adaptive immune response to invading pathogens and structurally altered proteins that can be found in cancers. By providing functional insights into the molecular mechanism of T cell activation, we will not only provide fundamental knowledge of receptor signalling but also specific details of T cell receptort triggering that may lead to the development of new therapeutic strategies to control T cell activation.Read moreRead less
Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.Read moreRead less