Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and w ....Discovering genes and mechanisms regulating immune responses. The Fellowship will retain and expand a pioneering Australian research program, and attract to Australia major international investment and technology linkages, making use of the DNA sequence of humans and other mammals to advance understanding of immunity and infection control in public health, agriculture and industry. The program will build on Australia's pre-eminent research strengths in the field of immunity and infection, and will create new knowledge and resources to improve human and animal health through vaccines, pharmaceuticals and public health policy. Read moreRead less
The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, ....The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, and the mechanisms indicative of effective immune cell differentiation will be identified. This proposal will provide insights into key mechanisms that result in reprogramming of immune cell function and memory and have implications for understanding general cellular differentiation.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individu ....Evolution in microsatellite DNA: testing models of mutation in an Australian marsupial. We aim to compare mutational events between microsatellite loci that vary in their exposure to recombination. We are able to do this because of a remarkable finding that Australian brushtail possums have multiple occurrences of a single microsatellite repeat element within the Y-chromosome and among autosomal loci. We will compare variation between the Y-linked and non Y-linked loci within and among individual possums and use those comparisons to distinguish between recombinant and non- recombinant mutational mechanisms. These data will provide new insights into the mutational mechanisms that drive variation in these most important molecular markers.Read moreRead less
Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate ch ....Sex in Dragons: Evolution of sex determination in reptiles. Australia is a leader in sex determination research with major advances in our understanding attributable to Australian researchers and laboratories. This project will contribute to our prestige as a nation capable of contributing cutting edge research directions and stimulating ideas in human sex determination. Moreover, many reptiles have temperature-dependent sex determination, and so would appear appallingly vulnerable to climate change. Our project, will bring improved understanding of sex determination in reptiles, identify evolutionary responses of reptiles to climate change, and assist by informing society on how we might manage this issue into the future conservation of these unique Australian reptiles. Read moreRead less
Sex in Dragons: The molecular basis of genetic and environmental sex determination. How animals determine sex has been debated over decades. Particularly mysterious is that sex is determined by genes in some animals, and by temperature in others. We will study closely related dragon lizards which determine sex via genes (GSD) or temperature (TSD). We will use novel genetic, molecular and cytological aproaches to discover genes and chromosomes that control sex determination in the GSD species, an ....Sex in Dragons: The molecular basis of genetic and environmental sex determination. How animals determine sex has been debated over decades. Particularly mysterious is that sex is determined by genes in some animals, and by temperature in others. We will study closely related dragon lizards which determine sex via genes (GSD) or temperature (TSD). We will use novel genetic, molecular and cytological aproaches to discover genes and chromosomes that control sex determination in the GSD species, and explore their homologues in the TSD species. We expect this study will provide new insights to mechanisms of sex determination in all vertebrates, and demonstrate how genes and the environment interact to control the process.Read moreRead less
Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to ....Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to 're-run the evolutionary tape', but the Y chromosome has been left out of whole genome sequencing because it is hard to do efficiently. We developed a novel technique to isolate DNA sequences and genes on the Y chromosome in three species of marsupials, which are especially valuable because they are so different from human and mouse.Read moreRead less
Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the ....Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the proposition that sex determination results from the interaction between environmental influences and an underlying genetic component.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less