Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene exp ....Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene expression data supports homology between sponge and eumetazoan tissues and body plans. This project could illuminate the evolutionary history of the animal body plan.Read moreRead less
Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery an ....Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery and genomic environments needed for retrotransposition are undefined. This project aims to use models to uncover the mechanisms that control retrotransposition. This is expected to reveal more about human origins.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
Discovery Early Career Researcher Award - Grant ID: DE190100085
Funder
Australian Research Council
Funding Amount
$414,864.00
Summary
Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is ach ....Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is achieved by examining the molecular pathways that are activated following genetic mutation. This project is expected to strengthen Australian reputation in evolutionary genetics, and in turn enhance our understanding of how organisms adapt to changing environments.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.
Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways m ....Is 'junk DNA' involved in gene editing in human cells. Exciting results suggest that non-coding RNAs (ncRNA), some of which emanate from regions in the human genome traditionally known as “junk DNA”, actually function to regulate protein-coding gene transcription. The goal of this project is to explore the role of ncRNAs on a genome-wide level to determine those proteins involved in this process and to what extent this process results in directed genome editing. Knowledge of the ncRNA pathways may lead to a novel methodology to activate silenced genes as well as determine the role of ncRNAs in genome evolution.Read moreRead less
Genetic And Evironmenal Risk Factors For Melanoma: Translation Into Behavioural Change
Funder
National Health and Medical Research Council
Funding Amount
$250,900.00
Summary
GenoMEL, formerly known as the Melanoma Genetics Consortium, has focused on the identification of familial high penetrance melanoma genes. The joint programme of research has been very successful in the identification of susceptibility genes and developing joint data collection for gene-environment interaction studies. In order to continue its proactive role, GenoMEL wishes to develop a multidisciplinary European platform, directed towards: 1. developing shared resources and activities 2. identi ....GenoMEL, formerly known as the Melanoma Genetics Consortium, has focused on the identification of familial high penetrance melanoma genes. The joint programme of research has been very successful in the identification of susceptibility genes and developing joint data collection for gene-environment interaction studies. In order to continue its proactive role, GenoMEL wishes to develop a multidisciplinary European platform, directed towards: 1. developing shared resources and activities 2. identification of new susceptibility genes and understanding the role of these genes in tumours 3. investigation of genotype-phenotype interaction and gene-environment interaction for known susceptibility genes 4. investigation of attitudes to risk of melanoma in Europe, and translation of that risk perception into behavioural change 5. spreading excellence by creating a widely accessible web-based content management system (CMS) to address prevention, early detection, dealing with the diagnosis of melanoma and genetic counselling. Through GenoMEL's jointly executed research, groups will support the network's goal to maintain excellence in research, increase institutional integration and create an enduring structure of translational melanoma genetics research in Europe and other countries. European integration will enhance dialogue, disseminate expertise and resources, provide training and allow mobility of scientists within Europe. It is aimed to keep the network open and dynamic by adding new partners, especially in Eastern Europe where melanoma incidence rates may rise most precipitously in the near future, if the expected increase in wealth results in greater levels of sun exposure. There will be participation from four new European groups and others from Australia, the USA and Israel to capitalize on latitudinal (sun exposure) differences between these groups.Read moreRead less
Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a ....Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a red blood cell line. Simultaneously, this project aims to generate fundamental insights into mechanisms of human gene regulation. The technological and biological outcomes of this project will be of benefit for future gene editing applications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100199
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Determining the mechanisms of transgenerational epigenetic inheritance. Although previously controversial, there is now little doubt that transgenerational inheritance of epigenetic marks can occur. This phenomenon is difficult to study in humans and many model organisms, in part due to long generation times. To avoid this difficulty, this project will use genetic and molecular biology approaches in the model organism Caenorhabditis. elegans. The project will utilise a robust assay for transgene ....Determining the mechanisms of transgenerational epigenetic inheritance. Although previously controversial, there is now little doubt that transgenerational inheritance of epigenetic marks can occur. This phenomenon is difficult to study in humans and many model organisms, in part due to long generation times. To avoid this difficulty, this project will use genetic and molecular biology approaches in the model organism Caenorhabditis. elegans. The project will utilise a robust assay for transgenerational epigenetic inheritance established to identify a collection of genes involved in the process and will determine the interplay between chromatin modifications and small RNA molecules. This project aims to determine the exact epigenetic mark that is transmitted and the mechanisms by which the transmission occurs.Read moreRead less
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