Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.
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
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
Epigenetic regulation of centromere and telomere chromatin. Epigenetics is a system that turns genes on and off without sequence alterations in the DNA. This process works by attaching chemical tags, known as epigenetic marks, to DNA. Centromeres and telomeres are chromosomal DNA domains essential for faithful chromosome segregation and genome stability. Their function and structural integrity are tightly regulated by specific epigenetic marks. This project aims to assess the functions of key ep ....Epigenetic regulation of centromere and telomere chromatin. Epigenetics is a system that turns genes on and off without sequence alterations in the DNA. This process works by attaching chemical tags, known as epigenetic marks, to DNA. Centromeres and telomeres are chromosomal DNA domains essential for faithful chromosome segregation and genome stability. Their function and structural integrity are tightly regulated by specific epigenetic marks. This project aims to assess the functions of key epigenetic factors including chromatin remodelers, histone variants and non-coding RNA in controlling centromere and telomere activity. The data should describe novel pathways that maintain the identity, transcription silencing, DNA replication fidelity and structural stability at these domains.Read moreRead less
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing pa ....DNA methylation in insect social evolution. This project will investigate the evolutionary relationship between DNA methylation and the advanced sociality displayed by bees, ants and wasps. The project will map DNA methylation across the social insects and test whether it has coevolved with sociality. It will also determine how a vital social cue, the queen pheromone, influences the worker methylome. Finally, it will apply quantitative genetic and methylomic methods to wild insects, revealing patterns of selection and inheritance in epigenetic and phenotypic traits. By combining genomic and evolutionary methods, the project will advance the ongoing debate about the importance of methylation to sociality and extreme phenotypic plasticity. It will contribute to a quantum leap in our understanding of DNA methylation and sociobiology and mark the first application of quantitative genetics to wild insects.Read moreRead less
HEN1 is a regulator of piRNA metabolism, transcriptional regulation and mammalian male fertility. This project is to define the biochemistry of a previously uncharacterized protein in male fertility using a unique mouse model and innovative DNA and protein technologies. This project will define a novel, and essential, pathway for male fertility and may ultimately have relevance to the maintenance of health or improving fertility.
Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how tem ....Sex determination in dragons: Genetics, epigenetics and environment. This project aims to discover the master sex-determining gene in a reptile, how that gene is differentially regulated in males and females and by temperature, and to identify evolutionary drivers of transitions between genetic and environmental sex determination. In many reptiles, like mammals, chromosomes determine sex. In others, the temperature at which their eggs are incubated determines sex. This project will study how temperature reverses chromosomal sex determination in dragon lizards. This could show how climatic extremes affect the biology of climate sensitive reptiles, and understand their vulnerability to climate change.Read moreRead less
Reprogramming maternal and paternal genomes during development: new perspectives from marsupials. This project will use marsupials to examine programming of the germ cell lineage (cells that become eggs and sperm) and the evolution of these mechanisms that control their development. Using the unique features of our Australian native animals, this research will contribute to the understanding of the transmission of life.
Solving the puzzle of complex disease - genes and their interactions with the environment. Many human diseases are caused by the interplay of genetic predisposition (nature) and the environment (nurture); but their causes remain a mystery, since much past research has focused on these aspects in isolation. This project will aim to better understand these complex diseases using a multi-factorial approach that brings both nature and nurture together.