Production Of Humanised Mouse Models For Haemoglobin E And 0-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$280,693.00
Summary
The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models ....The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models will be of direct value in the identification of commercially relevant contraceptive targets, as well as furthering our understanding of male reproductive function.Read moreRead less
Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic fr ....Unlocking the secrets of metabolic variation in a highly diverse bacterium. This project aims to explore metabolic diversity of Klebsiella pneumoniae, a bacterium relevant to the agricultural, veterinary, medical and biotechnology industries. It is expected to reveal significant insights into the biology of this diverse organism via an innovative combination of DNA sequence analyses and metabolic modelling. Expected outcomes include 4500 novel metabolic models and a novel population metabolic framework. This should provide major benefits for understanding bacterial ecology and evolution, and for future studies seeking to optimise industrial processes or prevent disease. It will also directly contribute to building Australia’s capacity in computational biology- a key driver of biotechnology innovation.Read moreRead less
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less
Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our underst ....Insulin transport into the central nervous system. This project aims to understand transportation of peripheral insulin into the central nervous system and how it maintains energy balance. Insulin is essential for normal physiological functioning in the periphery and central nervous system, but some circumstances, including high-fat diets, reduce insulin signalling in the brain. This project examines the mechanisms of insulin transport into the central nervous system, and may improve our understanding of blood brain barrier insulin transport and dysfunction.Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.
Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature ....Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature muscle types and patterns. The intended outcome of this research is to generate understanding of the complex molecular basis of muscle patterning in the simple paradigm of the zebrafish myotome that could be applied across the vertebrate phylogeny.Read moreRead less
Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the s ....Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the simpler liverworts to more complex flowering plants. The project may generate new understanding of the principles of how genes and hormones control the architecture of plant shoot systems, and support the targeted selection of new agricultural plants.Read moreRead less
3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untra ....3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untranslated region (UTR) dynamics in eukaryotic cell biology. This project expects to significantly advance the understanding of eukaryotic gene function and gene regulation, critical in an age of personalised genomic medicine.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100114
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as ....High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as well as validation of next generation sequencing data. The information generated is crucial to advancing knowledge in important research fields including infection and immunity, regenerative medicine, immune responses, biomarker discovery, drug discovery, biotechnology and agriculture.Read moreRead less