Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and dete ....Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and determine the architecture of several chromatin states with unique functional implications inside the cell. This will unravel the molecular instructions that define how our genomes are organised, significantly advancing our knowledge of fundamental eukaryotic genome biology and paving the way for the future development of new tools and therapies.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
Tracking factor footprints to reveal the intricacy and control of translation initiation. Messenger ribonucleic acid (RNA) translation is required for all of life and knowledge of how it works is central to modern life sciences. This project will develop novel ways of studying translation, generating entirely new descriptions of its inner workings that may transform knowledge of gene function and its use in medical and biotechnological processes.
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.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
Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated w ....Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated with painful and often lethal co-morbidities.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent ....Understanding disease resistance gene evolution across the Brassicaceae. Pan genomes represent the diversity of a species, including structural and sequence variation, which cannot be provided by a reference genome alone. In this project we will characterise resistance gene diversity across the Brassicaceae pan genomes. Through comparison with resistance gene diversity in cultivated Brassica species we will understand selection underlying resistance gene evolution in wild species and subsequent domestication and breeding. Knowledge on how variation affects disease susceptibility, especially to the devastating fungal pathogen blackleg, and contributes to phenotypic variation, will lead to improved plant protection strategies and increased crop resilience.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
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