Discovery Early Career Researcher Award - Grant ID: DE130100614
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Novel statistical algorithms and methods to quantify and partition pleiotropy between complex traits in populations. A fundamental question in biology is how common genetic effects are shared between traits or groups. For example, is cognition or human behaviour genetically identical across genders or across human population groups? This project will address these questions using multiple independent genome-wide association studies.
Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key featur ....Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key feature in biology, which relates to dissecting the complex mechanism of association and interaction. The proposed statistical model implemented in a context of a novel design based on multiple GWAS data sets is a paradigm shifting-tool with applications to multiple industries.Read moreRead less
Estimating genotype-environment interaction using genomic information. This project aims to develop statistical methods that can explore genotype–environment interaction at the genomic level using genome-wide single nucleotide polymorphisms or sequence data. It plans to estimate how the effects of genetic variants change with changing environmental conditions and how overall genetic variance changes due to changing effects in specific gene regions. It plans to deliver statistical models and meth ....Estimating genotype-environment interaction using genomic information. This project aims to develop statistical methods that can explore genotype–environment interaction at the genomic level using genome-wide single nucleotide polymorphisms or sequence data. It plans to estimate how the effects of genetic variants change with changing environmental conditions and how overall genetic variance changes due to changing effects in specific gene regions. It plans to deliver statistical models and methods and an efficient algorithm implemented in software, which would broadly benefit the field of complex trait genetics. Methods to estimate genotype–environment interaction effects at the genomic level would help elucidate complex biological systems, including human genetic response to changing environmental factors and the potential adaptation of animals to changing environmental conditions.Read moreRead less
Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic m ....Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic mutation in individual plants, providing an unprecedented level of detail into an important but understudied source of biological variation. By applying these methods to an iconic experimental population, This project aims to provide the first insights into the genome-wide causes and consequences of somatic mutation in plants.Read moreRead less
Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction wi ....Genetic variation of transcriptional control. Genetic variation is a key cause phenotype differences in humans, animals, and plants and so of great economic importance. Despite its proven importance to human diseases, ?quantitative? variation in the amount of gene expression rather than ?qualitative? protein sequence changes, has not been systematically studied. We have developed a powerful method to identify genetic causes of quantitative variation using crosses of inbred mice in conjunction with microarray techniques to analyse expression of thousands of genes simultaneously. These studies will be extended to humans and be significant to wide areas of biological and commercial activity.Read moreRead less
Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply ....Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply Sequential Monte Carlo to update phylogenetic analyses continuously as new data arrives. Expected outcomes include new knowledge of statistical algorithms for evolutionary analysis, relevant to biological disciplines beyond infectious disease; and enhanced capacity for infectious disease analysis. Read moreRead less
How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly iden ....How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly identified molecular diversity in the ribosomal RNA gene repeats. Outcomes include new paradigms for how the ribosomal RNA gene repeats drive protein synthesis and genome structure, and a blueprint to develop novel genomics applications for human health, biotechnology, and agriculture.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101210
Funder
Australian Research Council
Funding Amount
$451,634.00
Summary
Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromati ....Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromatin pairs; ii) Comperehensive maps of regulatory interactomes in 61 tissues & cells, which will provide a roadmap for interpreting & prioritising noncoding variants.
This should provide significant benefit to Australia's capacity for cutting-edge genomics research through fundamental understanding of gene regulation mechanism.Read moreRead less
The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some femal ....The roles of relatedness and reproductive success in complex social systems of dolphins. Theories of the role of genetic relatedness and reproductive success in mammalian social behaviour have mostly been restricted to primates and carnivores. Coexisting alternative strategies within one population of bottlenose dolphins (Shark Bay WA) offer unprecedented opportunities for such investigations. The male alliances? complexity is unparalleled outside humans, and may require new theory. Some female lineages show tool-use - rare outside humans, and virtually unknown in marine species. Our behavioural and genetic database has exceptional size, detail and duration for marine mammals, and is most valuable if continued while known individuals' offspring reach a stage where they can be sampled.Read moreRead less
Fire, bees and other disturbances: the basis for variation in genetic diversity in long-lived plants. An understanding of processes generating temporal and spatial patterns of genetic diversity in perennial plants must underpin successful conservation. Our long-term study will exploit systems in the family Proteaceae in which we have completed foundation studies. We will develop and extend molecular techniques to measure (i) genetic changes from seed to adult, (ii) gene flow by different pollina ....Fire, bees and other disturbances: the basis for variation in genetic diversity in long-lived plants. An understanding of processes generating temporal and spatial patterns of genetic diversity in perennial plants must underpin successful conservation. Our long-term study will exploit systems in the family Proteaceae in which we have completed foundation studies. We will develop and extend molecular techniques to measure (i) genetic changes from seed to adult, (ii) gene flow by different pollinator classes, and (iii) genetic contamination by foreign gene pools, in systems affected by introduced pollinators and natural and cultivar hybridization. Most importantly, we will use fire as an accelerant of generational change and test fitness consequences of changes in genotypic diversity.Read moreRead less