Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evol ....Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evolutionary mechanisms and ultimately regenerative medicine.Read moreRead less
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Defining how molecular switches program cell identity during development. Aims: This project aims to investigate how molecular switches known as transcription factors, work together to turn genes on or off to program cell identity during development.
Significance: This project expects to generate new knowledge in the area of genetics and developmental biology using collaborative, cutting edge technologies.
Outcomes: Expected outcomes of this project include the identification of new genes impor ....Defining how molecular switches program cell identity during development. Aims: This project aims to investigate how molecular switches known as transcription factors, work together to turn genes on or off to program cell identity during development.
Significance: This project expects to generate new knowledge in the area of genetics and developmental biology using collaborative, cutting edge technologies.
Outcomes: Expected outcomes of this project include the identification of new genes important for programming the identity of cells that comprise our blood vessels, lymphatic vessels and circulating blood cells.
Benefits: Data generated will underpin the development of approaches to program/reprogram stem cells to produce mature cells for transplantation or tissue engineering purposes ex vivo.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101210
Funder
Australian Research Council
Funding Amount
$451,634.00
Summary
Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromati ....Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromatin pairs; ii) Comperehensive maps of regulatory interactomes in 61 tissues & cells, which will provide a roadmap for interpreting & prioritising noncoding variants.
This should provide significant benefit to Australia's capacity for cutting-edge genomics research through fundamental understanding of gene regulation mechanism.Read moreRead less
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.Read moreRead less
Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understandin ....Evolution and function of mammalian sex chromosomes. Research on iconic Australian mammals has profoundly reshaped our understanding of reproductive biology and sex chromosome evolution. In this project we combine unique expertise, international collaboration and novel genetic information about Australia's unique egg-laying mammals (echidna and platypus) to investigate major aspects of reproduction. This work will address fundamental aspects of sex chromosome biology and advance our understanding of mammalian reproduction. The knowledge gained will have application in captive breeding and conservation of these extraordinary Australian mammals. The project also provides opportunity to train research students in cutting edge molecular biology and informatics.Read moreRead less
How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to und ....Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to understanding how new mutations arise in sperm and potentially affect offspring phenotype, adaptation and evolution. As chemicals, drugs and diet can affect epigenetic function, our studies will also contribute to determining how epigenetic inheritance affects environmental, agricultural and healthcare outcomes.Read moreRead less
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