Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line ....Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line are made into proteins. The project will improve our understanding of the human genome and deliver cutting edge methodology applicable for genome annotation in all living organisms.Read moreRead less
Heme oxygenase integrates cellular responses to oxygen stress. A deficiency in the protein heme oxygenase-1 causes severe biological consequences including retarded development, chronic inflammation and increased susceptibility to age-associated diseases. By illuminating how heme oxygenase-1 improves cell function the project will eventually assist in preventing or slowing the serious age-associated disorders.
The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by def ....The Role of DNA Methylation in Transcription Factor Activity. Although it is well established that gene expression is closely correlated with DNA methylation, its role in regulating the activity of DNA-binding proteins remains unclear. It has recently been shown that Krüppel-like transcription factors (KLF) have distinct binding preferences for methylated DNA sequences. This project aims to investigate how the activity of transcription factors is dependent upon targeting of methylated DNA by defining the genome-wide set of sites and structural domains critical for binding. It also will explore the functional significance of these sequences using assays that investigate the importance of DNA methylation in KLF mediated cellular reprogramming to the pluripotent state.Read moreRead less
Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synth ....Engineering a chromatin looping factor for artificial gene regulation. This project aims to define mechanisms of chromatin looping and gene activation by a widely expressed mammalian protein. The project will establish if the functions of this protein are modulated by the binding of small molecules, whether it can act in conjunction with closely related proteins, and if post-translational modifications regulate looping and gene activation. Using protein engineering the project will develop synthetic looping factors that can switch on a wide array of target genes. The project aims to answer fundamental questions about how proteins can establish and maintain physical loops in DNA to modulate gene expression. The project will also develop research tools that might ultimately correct diseases caused by the faulty expression of genes.Read moreRead less
How do cells regulate the synthesis and localisation of coenzyme Q? The aims of this project are to identify how cells regulate the synthesis and the distribution of coenzyme Q between different organelles, and how these processes are affected when cells experience various conditions of stress. Coenzyme Q is a fat-soluble molecule present in all cell membranes and essential for normal cell function. Despite this, relatively little is known about the systems that regulate the synthesis and cellul ....How do cells regulate the synthesis and localisation of coenzyme Q? The aims of this project are to identify how cells regulate the synthesis and the distribution of coenzyme Q between different organelles, and how these processes are affected when cells experience various conditions of stress. Coenzyme Q is a fat-soluble molecule present in all cell membranes and essential for normal cell function. Despite this, relatively little is known about the systems that regulate the synthesis and cellular location of coenzyme Q. The project plans to identify the genes and proteins required for coenzyme Q regulation of sub-cellular distribution in unstressed and stressed cells. In doing so, the project could provide a greater understanding of the ways cells maintain normal coenzyme Q levels and respond to stress.Read moreRead less
Tuning mesenchymal stem cell lifespan, performance, and differentiation. This project aims to fully characterise a unique molecular process that strongly modulates mesenchymal stem cell lifespan and behaviour. This work is significant, as it is expected to reveal new concepts underpinning the mechanistic actions of classical structural proteins. It will also shape a more nuanced understanding of the context-dependent mechanical and biochemical signals that regulate stem cell fate and function. E ....Tuning mesenchymal stem cell lifespan, performance, and differentiation. This project aims to fully characterise a unique molecular process that strongly modulates mesenchymal stem cell lifespan and behaviour. This work is significant, as it is expected to reveal new concepts underpinning the mechanistic actions of classical structural proteins. It will also shape a more nuanced understanding of the context-dependent mechanical and biochemical signals that regulate stem cell fate and function. Expected outcomes include new knowledge surrounding native extracellular matrix and stem cell biology, and the development of strategies to define and tailor stem cell properties. This work is anticipated to drive new technologies that can efficiently and robustly manipulate stem cells for diverse functional applications.Read moreRead less
How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is funda ....How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is fundamental to the development of all living organisms, this work could have wide implications for understanding all biology – from microbes, insects and plants to humans.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100008
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and ....Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and microbiology. Moreover, this component of the University's research portfolio plays a major role in the postgraduate training of young Australian scientists who will, in turn, fuel future developments in both the life sciences and biotechnology industries.Read moreRead less