Discovery Early Career Researcher Award - Grant ID: DE200101323
Funder
Australian Research Council
Funding Amount
$427,098.00
Summary
Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computationa ....Structure guided mapping of protein interactions and their perturbation. Protein interactions are central to most biological processes, and significant effort has been devoted to trying to unravel these complicated networks. This project aims to develop new approaches to better understand these interactions, and the consequences of their perturbation. The main expected contributions will be: (i) methods to identify likely protein interaction sites using population conservation; (ii) computational approaches to assess the effects of any type of mutation on the interaction; and (iii) an understanding of how disruption of a specific interaction can affect the complicated biological network within a cell. Read moreRead less
Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400Â million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what spe ....Reconstructing proteins to explain and engineer biological diversity. The aim of this project is to develop computational methods to construct entirely new proteins. Computational reconstruction of enzymes that have been extinct for over 400Â million years has revealed remarkable opportunities for biotechnological innovation. The intended outcomes are to develop bioinformatics methods to broaden the scope of ancestral protein reconstruction to include protein super-families, to establish what specific changes led to the evolutionary success of a protein, and to re-run evolution to generate proteins that perform in conditions suitable for industrial and agricultural applications, in particular the production of hydroxylated fatty acids for bioplastics. By examining proteins from many life forms, the project plans to develop a novel bioinformatics strategy to understand their evolution and engineer new proteins for use in production of chemical commodities.Read moreRead less
The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.Read moreRead less
Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across f ....Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across fly species and vertebrates, and their functional effect on testis morphogenesis and distortion of female/male sex-ratio. The project also studies splicing-dependent small RNAs and miRNA-target interaction. This research could have applications from animal development to human pathology.Read moreRead less
The systems biology of stem cells. Using new bioinformatic methods, this project aims to identify new classifiers of different stem cell populations, develop statistical models that address population heterogeneity and provide molecular predictors of the differentiation potential of stem cells. Understanding, predicting and directing the processes of differentiation are major goals in the disciplines of stem cell biology, developmental biology, tissue engineering and regenerative medicine. Molec ....The systems biology of stem cells. Using new bioinformatic methods, this project aims to identify new classifiers of different stem cell populations, develop statistical models that address population heterogeneity and provide molecular predictors of the differentiation potential of stem cells. Understanding, predicting and directing the processes of differentiation are major goals in the disciplines of stem cell biology, developmental biology, tissue engineering and regenerative medicine. Molecular atlas projects have successfully revealed rules of genome output and regulation, by mining patterns that are evident across multiple cell types and datasets. By applying this philosophy to relevant, well-curated stem cell experiments, this project aims to create new methods for the integration and interrogation of smaller individual datasets. These methods should have broad utility and enable new avenues in tissue engineering.Read moreRead less
Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line ....Exploring novel coding genomic features through integrative proteogenomics. Knowledge of the full extent to which the human genome is made into proteins is of fundamental importance in the study of health and disease. New technological advances are now enabling functional studies of genomes with increasing detail. This project aims to develop and apply cutting edge bioinformatics methods to perform an integrative and comprehensive exploration of the extent to which the genes of a human cell line are made into proteins. The project will improve our understanding of the human genome and deliver cutting edge methodology applicable for genome annotation in all living organisms.Read moreRead less
Formation of boundaries in the developing embryo. This project aims to decipher how the boundaries between the different organs are established in the developing embryo. The project aims to identify the components of the gene regulatory network that controls lateral plate mesoderm formation, develop a mathematical model that can explain how the domains are formed within this region, and validate novel interactions in vivo in zebrafish. The expected outcome of the project is to reveal how the pro ....Formation of boundaries in the developing embryo. This project aims to decipher how the boundaries between the different organs are established in the developing embryo. The project aims to identify the components of the gene regulatory network that controls lateral plate mesoderm formation, develop a mathematical model that can explain how the domains are formed within this region, and validate novel interactions in vivo in zebrafish. The expected outcome of the project is to reveal how the progenitors of our body parts are instructed to be positioned at the right time and at the right place in the embryo. This project should provide significant benefit such as the expansion of Australia's knowledge base and research capability in cross-disciplinary science.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
Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological pro ....Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological processes will be elucidated, specifically the robustness of cellular systems. Expected outcomes include a suite of novel tools that will push the boundaries of current bioinformatics solutions with potential to deliver significant benefits to every domain of biological science, particularly tissue engineering and synthetic biology.Read moreRead less
Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water ....Sequencing and assembling microbial community metagenomes in real-time. This project aims to assemble metagenomes directly from environmental samples using nanopore sequencing. Short-read approaches to metagenomics cannot assemble mixed genomes from an environmental sample, so focus on describing which species and genes are present. Long-read nanopore sequencing enables the assembly of full genomes of multiple species in a sample. Assembling complete genomes in important resources such as water and soil should lead to deeper understanding of the dynamics, variation and transfer of genetic material within these resources’ microbial communities, strategies to manage microbial diversity, and improved productivity and long-term sustainability for these resources.Read moreRead less