Discovering the molecular controls of epigenetic inheritance . This project aims to investigate the way in which acquired traits can be inherited. The environment that an individual is exposed to can change the characteristics of not only that individual, but also their children and grandchildren. We do not yet understand the mechanisms by which this “epigenetic inheritance” occurs. Using interdisciplinary approaches, this project combines the power of the model organism Caenorhabditis elegans ....Discovering the molecular controls of epigenetic inheritance . This project aims to investigate the way in which acquired traits can be inherited. The environment that an individual is exposed to can change the characteristics of not only that individual, but also their children and grandchildren. We do not yet understand the mechanisms by which this “epigenetic inheritance” occurs. Using interdisciplinary approaches, this project combines the power of the model organism Caenorhabditis elegans with cutting-edge single molecule microscopy techniques to determine the molecular mechanisms by which the environment can impact future generations. This should ultimately provide society with the means to harness the power of epigenetics.Read moreRead less
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms t ....Comparing properties of innate immune proteins of bats and humans. Supra-molecular protein complexes known as signalosomes drive our innate immune response by forming large signaling hubs capable of recruiting downstream effectors. This project aims to compare the properties and structure of human and bat signalosomes and discover the molecular origins of the “supra-immunity” of bats. In this context, the project expects to generate new knowledge concerning the fundamental molecular mechanisms that regulate the signalosomes. The intended outcome is to answer the long-standing question of control of speed and amplitude of innate immune response at the molecular level. Both locally and internationally, this new approach should provide benefits across structural biology, molecular evolution and biotechnology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100992
Funder
Australian Research Council
Funding Amount
$448,237.00
Summary
New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to devel ....New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to develop novel machine-learning approaches to capture protein flexibility and shape. This proposal will advance fundamental understanding of the TSC-mTOR pathway and build transformative methodologies to study flexible proteins more broadly.Read moreRead less
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
Targeting Iron Piracy From Host Proteins By Neisseria And Haemophilus Spp. For The Development Of Novel Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
The bacteria that cause the sexually transmitted infection gonorrhoea and meningococcal disease are a serious health concern. In order to cause disease, these bacteria must obtain the nutrient iron from our bodies. This proposed research will use cutting edge technologies to understand on a molecular level how these bacteria obtain iron during infection. It will then apply this knowledge to develop molecules that prevent these bacteria from obtaining iron, as a means of treating these diseases.
Tackling Antimicrobial Resistance In Neonatal Sepsis: Australia And Beyond
Funder
National Health and Medical Research Council
Funding Amount
$566,164.00
Summary
This project aims to establish clear data regarding the burden of antibiotic resistance in neonates in Australia & in our local South East Asian region. This will be achieved by establishing systematic data collection for infections with multi-resistant bacteria in Australian neonatal intensive care units, reviewing published literature regarding the cause of infections in South East Asian neonates, and continuing collaborative work to establish a new treatment regimen for neonatal sepsis.
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mt ....Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mtDNA does not suffer mutational meltdown and is shown to adapt. This project will explain how, proposing that the combination of two traits, uniparental inheritance and multiple genomes per cell, make up for the lack of sex. This project expects to provide an explanation for the evolutionary question of what keeps mitochondria healthy, important as mitochondria affect ageing and health.Read moreRead less
Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding ....Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes. Expected Outcomes and Benefits: This proposal will provide novel targets and methodology for gene modulation with broad applications from biology to environmental sciences.Read moreRead less