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.
How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the h ....How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the human counterparts of the Drosophila proteins studied here, function similarly. Benefits will be provided in the form of job creation, and new knowledge in fundamental aspects of life, including brain development and cell fate maintenance.Read moreRead less
How protein and RNA cargo are sorted into exosomes. This project aims to understand how proteins and RNA are selected for packaging into exosomes and participate in the biological functions mediated by these vesicles. Exosomes are small membranous extracellular vesicles released by cells which contain protein and RNA cargo and are involved in intercellular communication. Determining how the exosome cargo is selected and related to its function in intercellular communication is expected to show h ....How protein and RNA cargo are sorted into exosomes. This project aims to understand how proteins and RNA are selected for packaging into exosomes and participate in the biological functions mediated by these vesicles. Exosomes are small membranous extracellular vesicles released by cells which contain protein and RNA cargo and are involved in intercellular communication. Determining how the exosome cargo is selected and related to its function in intercellular communication is expected to show how these vesicles maintain cellular homeostasis. The findings will expand knowledge in the area of microRNA biology, proteomics and develop expertise in bioinformatics.Read moreRead less
Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validat ....Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validation of their activity and characterisation of their potential to contribute new bacterial host metabolism. This should provide benefits, such as advancement to our understanding of bacteriophages, improved bioinformatic software, and a characterised collection of commercially valuable bacterial strains and phages.Read moreRead less
Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dime ....Empirical and computational solutions for multi-omics single-cell assays. Emerging single-cell sequencing technologies are transforming molecular cell biology, but identifying novel cell types and their functions requires the integration of highly heterogeneous data. The development of computational methods able to extract biologically relevant results is hindered by the lack of high-quality datasets. This project aims to develop novel sequencing methodologies and generate data to drive our dimension reduction multivariate method developments for data integration. By combining in silico and in vivo approaches, the project is anticipated to benefit scientists willing to work in cutting-edge single-cell research by providing useful protocols and tools to generate novel insights in cell biology. 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
Three-dimensional structure determination of biomolecular assemblies from sparse data of different length scales. New computer algorithms will be combined with sparse experimental structure restraints, obtained with novel protein chemistry technologies, to generate accurate three-dimensional (3D) models of proteins and protein assemblies in solution and in the solid state. The new strategies will greatly increase the number of protein targets amenable to rational drug design.
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
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.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