Leveraging Genomics Strategies To Generate Adult Neurons From IPSCs And Somatic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,593,336.00
Summary
Recent advances have made it possible to derive myriad specialized human cells from stem cells or by directly reprogramming cell identity. However, these derived cells are generally arrested at a fetal developmental stage, and do not mature to function like adult cells. We will use new genomic, epigenetic, cell reprogramming, and manipulation methods to discover how to derive mature cells, aiming to generate mature neurons for use in neurobiology research, disease modeling, and drug screening.
The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
Discovery Early Career Researcher Award - Grant ID: DE130101760
Funder
Australian Research Council
Funding Amount
$374,000.00
Summary
Uncovering the roles of key ribonucleases critical for post-transcriptional control of chloroplast gene expression. Higher plant chloroplasts harbour key biological processes that are essential to life on earth. Deciphering the roles of important plastid-targeted ribonucleases, central to post-transcriptional ribonucleic acid (RNA) processing events, is crucial to elucidate the genetic elements required to engineer chloroplast metabolic pathways to enhance productive crop yields.
Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for ....Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for important agronomic traits including disease resistance, flowering time and legume nitrogen fixation which will enable plant breeders to identify and apply novel genes and allelic variants for use in breeding programmes, accelerating the production of improved crop varieties.Read moreRead less
Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent ....Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent domestication and breeding. Knowledge on how variation affects disease susceptibility, especially to the devastating fungal pathogen blackleg, and contributes to phenotypic variation, will lead to improved plant protection strategies and increased crop resilience.Read moreRead less
The More the Merrier? Investigating copy number variation in Brassicas. This project intends to develop an understanding of how gene copy number variation affects disease susceptibility to help in the design of novel plant protection strategies. Gene copy number variants (CNVs) are segments of DNA that have been duplicated or lost in the genome of one individual or line with respect to another. CNVs have been shown to contribute significantly to phenotypic differences in humans, including diseas ....The More the Merrier? Investigating copy number variation in Brassicas. This project intends to develop an understanding of how gene copy number variation affects disease susceptibility to help in the design of novel plant protection strategies. Gene copy number variants (CNVs) are segments of DNA that have been duplicated or lost in the genome of one individual or line with respect to another. CNVs have been shown to contribute significantly to phenotypic differences in humans, including disease susceptibility, and the same seems to apply in plants. This project aims to apply the genome sequences for Brassica species to detect CNVs from re-sequencing data. Knowing how this variation affects an individual or line’s disease susceptibility, especially to the devastating fungal pathogen blackleg, could improve plant protection strategies and crop production.Read moreRead less
Characterization Of Novel Regulators Of Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature fu ....Mature red and white blood cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for epo to stimulate them to become mature functional cells. We have identified six molecules which interact with Lyn in red blood cells. We have shown that amolecule called HS1 is important for epo function in individual red blood cells and now we plan to investigate its functions in whole animals, including mice that lack the HS1 gene. We have also shown that a molecule called Trip1 is important for red blood cell development. Interestingly, this molecule also interacts with the thyroid hormone receptor and can influence the effects of epo and thyroid hormone on red blood cell development. The interplay between these two hormones will be looked at in more detail both at the cell and whole animal levels in normal mice and those lacking the thyroid hormone receptor gene. The third Lyn binding molecule we isolated is a novel gene-we have named it ankyrin repeat protein in line with the molecules it is related to. This gene is expressed in red blood cells and we aim to investigate what role it plays in the development of these cells. The fourth gene is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Its role in red blood cell structure will also be investigated. Finally, the last two molecule we have identified are both novel and are unrelated to any other known proteins. As above, the effects of these two molecules on red blood cell development will be investigated.Read moreRead less
The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this projec ....The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this project include uncovering the anatomical changes underpinning the origin of the vertebrate appendicular system. This should provide significant benefits as it will inform our own natural history and provide a paradigm for studying gene network
conservation, phylogenetic modifications, and the acquisition of novel structures.Read moreRead less
Regulatory design for water quality management in urban catchments. This project aims, through empirical research (i) to evaluate the effectiveness of current regulatory, quasi-regulatory and other policy strategies for water quality management in urban catchments (including total/integrated catchment management); (ii) to provide practical policy prescriptions concerning how through judicious regulatory and institutional design, those problems may be best addressed for the future; and (iii) adva ....Regulatory design for water quality management in urban catchments. This project aims, through empirical research (i) to evaluate the effectiveness of current regulatory, quasi-regulatory and other policy strategies for water quality management in urban catchments (including total/integrated catchment management); (ii) to provide practical policy prescriptions concerning how through judicious regulatory and institutional design, those problems may be best addressed for the future; and (iii) advance regulatory theory by developing a framework for understanding the relative effectiveness of different regulatory regimes in the context of urban catchment management. Its empirical focus is on the Swan-Canning river in Western Australia.Read moreRead less
Characterising structural variation in the canola genome. Characterising structural variation in the canola genome. This project aims to develop and apply genomic tools to identify and characterise structural genome variation in canola, a major Australian export crop, to better understand genome evolution and accelerate canola breeding. Advances in DNA sequencing revolutionise our understanding of crop genomes, their evolution and impact on the inheritance on agronomic traits. Variation of genom ....Characterising structural variation in the canola genome. Characterising structural variation in the canola genome. This project aims to develop and apply genomic tools to identify and characterise structural genome variation in canola, a major Australian export crop, to better understand genome evolution and accelerate canola breeding. Advances in DNA sequencing revolutionise our understanding of crop genomes, their evolution and impact on the inheritance on agronomic traits. Variation of genome structure between individuals could be important in the inheritance of important agronomic traits. Recent advances in technology permit the detailed characterisation of structural variation on a previously unfeasible scale. Anticipated outcomes are enhanced global food security, supporting rural Australian economies, and accelerating the improvement of other major crops.Read moreRead less