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
Untangling the plant Golgi apparatus: Functional proteomics to understand plant cell wall biosynthesis. The plant cell wall determines plant morphology and structure. It is also a major factor in food quality, and it is used as forage and is the raw material for a range of industries. A significant proportion of the cell wall is synthesised in a poorly studied cellular compartment known as the Golgi apparatus. This project intends to exploit unique isolation and analytical techniques in conjunct ....Untangling the plant Golgi apparatus: Functional proteomics to understand plant cell wall biosynthesis. The plant cell wall determines plant morphology and structure. It is also a major factor in food quality, and it is used as forage and is the raw material for a range of industries. A significant proportion of the cell wall is synthesised in a poorly studied cellular compartment known as the Golgi apparatus. This project intends to exploit unique isolation and analytical techniques in conjunction to further profile and characterise this structure in order to uncover new information about the complex interplay of components involved in plant cell wall biosynthesis. This information will be used to support approaches to manipulate cell walls to produce plant biomass optimised for agricultural and industrial applications.Read moreRead less
Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that c ....Novel antimicrobial target discovery by an integrated approach. The project aims to uncover the molecular targets of BDM-I, a novel antimicrobial candidate discovered by the start-up Australian company BioDiem Ltd. BDM-I is active against many drug resistant bacterial and fungal microorganisms and it is currently in pre-clinical development. However, the lack of resistant phenotypes makes it difficult to identify BDM-I’s mechanism of action. The project plans to use an integrated approach that combines a novel technique of in silico screening with experimental validation. Project outcomes are anticipated to include the first computational method to integrate target and ligand similarity for proteome-scale target and off-target discovery, which will advance the global fight against drug-resistant microorganisms.Read moreRead less
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
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
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
Discovery Early Career Researcher Award - Grant ID: DE150101777
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the ....Understanding the role of exosomes in intercellular communication. Exosomes, small packages released by cells, are powerful signalling organelles that can activate neighbouring cells by transferring proteins and RNA. Currently, it is unknown whether exosomes have similar membrane protein/lipid composition to that of the host cell. This project aims to explore the similarities and differences between the exosomal and host cell membranes in terms of the protein/lipid composition. In addition, the project aims to study how the proteins and RNA are packaged into exosomes. Membrane molecules that are detected only in the exosomes may have important signalling implications and may aid in the uptake/fusion of exosomes by/with target cells. The project aims to improve our understanding on signalling mediated by exosomes.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.