Membrane attack complex/perforin-like proteins in developmental and neurobiology. This project will aim to use the fruit fly as a model system to understand how members of the perforin-like superfamily, a family of proteins more usually associated with mammalian immunity, function in embryonic and neural development. These data will eventually provide central insight into human diseases such as cancer and autism spectrum disorder.
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
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughp ....Early animal evolution: reconstructing the last common metazoan ancestor through the analysis of developmental and structural genes in sponges. All animals, from the simplest invertebrates to humans, arose from a common ancestor. Reconstruction of this ancestor requires the comparison of metazoan developmental genetic architectures. Here we contribute to this pursuit by studying a phylogenetically and biological appropriate metazoan system - marine sponge embryos and larvae. Using high-throughput gene profiling techniques, we will analyse the developmental genetics underlying the sponge body plan. Commonalities shared between sponges and more sophisticated animals are likely to have been present in the "genetic toolkit" of the most ancient metazoan ancestor and, as such, is the genetic foundation from which all animal biodiversity arose.Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.Read moreRead less
Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechani ....Uniting histone and transcription factor codes. This project aims to establish the general features of the “histone code”. It is well established that gene expression patterns are determined in part by the deposition, recognition and removal of post-translational modifications on the histone proteins that package eukaryotic DNA. This project proposes that this "histone code" is in fact a specific example of a transcription factor code. The project aims to enhance our understanding of the mechanisms underlying gene regulation in plants and animals, and help to create improved strategies to optimise crop and farm animal properties and new-generation therapeutics.Read moreRead less
The role of Roquin in microRNA function and decay. The aim of this study is to understand how microRNAs (newly discovered genetic components that control cell growth and survival) function and are regulated. The expected discoveries will help understand how common cancers including breast cancer and autoimmune diseases emerge, and will help develop cutting edge genetic technologies.
The evolutionary transition from anaerobic to aerobic metabolism. This project aims to find out how life on Earth survived the revolutionary changes when cyanobacteria first released oxygen into the atmosphere. These events led to a transition from anoxic (oxygen-free) to oxic (oxygen-rich) conditions. A comparative genomic view across a series of photosynthetic organisms will be performed at the molecular level with ecological interpretation. Understanding of what metabolic changes occurred in ....The evolutionary transition from anaerobic to aerobic metabolism. This project aims to find out how life on Earth survived the revolutionary changes when cyanobacteria first released oxygen into the atmosphere. These events led to a transition from anoxic (oxygen-free) to oxic (oxygen-rich) conditions. A comparative genomic view across a series of photosynthetic organisms will be performed at the molecular level with ecological interpretation. Understanding of what metabolic changes occurred in response to the shifts in the environment will have wide implications for predicting the evolutionary events that are still occurring today, such as rapidly changing climatic conditions. This fundamental research will enhance Australia's profile in this field.Read moreRead less
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.Read moreRead less