How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the h ....How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the human counterparts of the Drosophila proteins studied here, function similarly. Benefits will be provided in the form of job creation, and new knowledge in fundamental aspects of life, including brain development and cell fate maintenance.Read moreRead less
Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron r ....Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron resolution, and how Hippo signalling modulates their behaviour, interaction with the genome and function. We anticipate our discoveries will stimulate new research, e.g. testing of how other signaling pathways regulate transcription. Intended benefits are creation of jobs and new knowledge on fundamental principles of life.Read moreRead less
Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will incl ....Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will include gain of substantial insight into molecular mechanisms underlying germline stem cell function and gene regulation within the male germline. This should provide significant benefits, including advancement of reproductive science and development of systems applicable for animal germline preservation and manipulation.Read moreRead less
Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This ....Regulation of histone methylation by polycomb-like proteins. This project aims to investigate how polycomb-like proteins regulate polycomb group (PcG) proteins and recruit them to their target genes. During the development of all multicellular organisms, PcG proteins are essential for keeping thousands of genes in a repressed state. PcG proteins are recruited to their target genes with the aid of their Polycomb-like protein cofactors, in a process that is poorly understood mechanistically. This project will determine the mechanism that underpins the recruitment and regulation of PcG proteins by polycomb-like proteins. Outcomes will have relevance for most development processes of multicellular organisms.Read moreRead less
How age & sex impact the transcriptional control of mammalian muscle growth. Maintaining healthy muscle is crucial throughout all stages of life. Aging is associated with the loss of muscle and older muscles are resistant to growth due to age-related changes in gene expression and responsiveness. Many genes are expressed differently in male versus female muscle, which may have implications for sex-differences in muscle growth and aging. This project will generate new knowledge on which genes and ....How age & sex impact the transcriptional control of mammalian muscle growth. Maintaining healthy muscle is crucial throughout all stages of life. Aging is associated with the loss of muscle and older muscles are resistant to growth due to age-related changes in gene expression and responsiveness. Many genes are expressed differently in male versus female muscle, which may have implications for sex-differences in muscle growth and aging. This project will generate new knowledge on which genes and biological pathways are crucial in determining mammalian muscle size and growth across the lifespan and between the sexes. Application of this knowledge may lead to future approaches to enable a healthy start to life and promote healthy aging in Australians and have implications for agriculture and muscle as a food source.Read moreRead less
About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock a ....About time; a new biology for the mineralocorticoid receptor . Temporal control of cell function aligns biological pathways with environmental cues and is critical for optimal heath in mammals. This project will shed light on how a hormone receptor, the MR, modulates time keeping of biological clock time in cells. We will bring together cutting edge genetic modals and bioinformatic approaches with a unique set of research models to define the interaction between the MR and the circadian clock and its role in the normal biology of the heart. New data will significantly enhance our understanding of the biology of MR and cortisol for the circadian time keeping function in peripheral tissues, and gain a clearer understand how our heart cells adapt to environmental circadian disruptors such as shift work. Read moreRead less
Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
Biomolecular condensates in mRNA-regulation in germ cells. This project aims to investigate how cells form microenvironments that are enriched for specific biological functions. Using a powerful combination of cutting-edge in vitro and in vivo experiments, the project will generate new knowledge in the emerging area of liquid-liquid phase separation. We will analyse the formation of germ granules that are required for fertility. The expected outcome is a transformational understanding of how liq ....Biomolecular condensates in mRNA-regulation in germ cells. This project aims to investigate how cells form microenvironments that are enriched for specific biological functions. Using a powerful combination of cutting-edge in vitro and in vivo experiments, the project will generate new knowledge in the emerging area of liquid-liquid phase separation. We will analyse the formation of germ granules that are required for fertility. The expected outcome is a transformational understanding of how liquid-liquid phase separation occurs in cells which, in the longer term, will have applications in biotechnology and disease treatment.Read moreRead less
The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-bioche ....The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-biochemistry, Next Generation Sequencing, and bioinformatics to answer long-standing questions in RNA processing. The project expects to significantly enhance our understanding of the mechanisms underpinning gene-expression control, benefitting Australia by positioning it as a world leader in the field of RNA Biology.Read moreRead less
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less