Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
Perceptual suppression mechanisms in the Drosophila brain. This project will investigate common processes underlying three means to losing conscious perception: selective attention, sleep and general anaesthesia. By studying these suppression mechanisms in a genetic model, the fly Drosophila melanogaster, fundamental processes will be highlighted that are required in the brain for maintaining perception in general.
Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the forma ....Defining the earliest events in lymphatic vasculature formation from veins. Vascular system development is one of the earliest events that occurs in the embryo. The entire lymphatic vascular system forms from the embryo’s early veins. This project aims to define the earliest molecular and cellular changes essential to form an entire second vessel network from just a few precursor cells in the embryo. The project aims to utilise zebrafish and mouse embryos to greatly expand knowledge in the formation of this essential vertebrate tissue. Ultimately, this is expected to provide new knowledge in stem and precursor cell differentiation, the evolution of complex organ systems and tissue formation. Outcomes may impact on future biotechnology in the areas of tissues engineering, stem cell differentiation and regeneration.Read moreRead less
Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion poly ....Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion polymorphism from population sequence data. Finally, the project will use this map to assess the functional impact and evolutionary role of inversions, by assessing their effect on quantitative traits and assessing measures of selection and population differentiation. Read moreRead less
Evolution and function of fragmented animal mitochondrial genomes. This project will reveal why animal mitochondrial genomes are in pieces, and how fragmented mitochondrial genomes evolve and function. This project will discover whether or not fragmented mitochondrial genomes have functional advantages. Knowledge generated from this project will lead to new approaches to mitochondrial genetic diseases in humans.
Molecular characterization of the role of menin in embryonic development. Menin is a protein that is necessary to prevent development of tumours. Deletion of menin in mice causes embryonic death. We think this is because menin is necessary in the placenta. This project will examine the role of menin in the fetus and the placenta, and provide information about how normal pregnancy and fetal growth is controlled.
Towards a new understanding of the reproductive system. The proposed analysis of the reproductive system will provide important new knowledge of gene regulation driving organ development. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.
Intron splicing regulates gene silencing in Arabidopsis. Defective gene regulation (i.e. how genes switch on and off) can cause severe genetic disease in both plants and animals, including humans. This project will use plants as a model to investigate a cause of defective gene expression, and should reveal possible avenues for therapeutic intervention to correct genetic defects in plants and animals.