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
Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated w ....Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated with painful and often lethal co-morbidities.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how the ....A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how these cell signaling proteins are organized into pathways and how this microorganism controls its complex growth and developmental cycle, we will be able to develop novel methods of control. We are at the fore front of international research and therefore uniquely placed to conduct this project.Read moreRead less
Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery an ....Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery and genomic environments needed for retrotransposition are undefined. This project aims to use models to uncover the mechanisms that control retrotransposition. This is expected to reveal more about human origins.Read moreRead less
A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance signif ....Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance significantly our understanding of mitochondrial biology, and will also have ramifications for other areas of protein transport.Read moreRead less
Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as ....Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as South Africa. The outcomes will provide new insight into the biological function of the novel GCs. Consequently, the new knowledge is critical to the development of novel biotechnological approaches to benefit sustainable agriculture in Australia.Read moreRead less
Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disea ....Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disease (AD) and/or Multiple Sclerosis (MS) in which the regulation of the actin cytoskeleton is affected.
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Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical rol ....Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical role in membrane trafficking. The proposed studies will provide important new insights into the molecular mechanisms underlying the function of both snapin and SNAREs, and membrane trafficking in general.Read moreRead less