Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a ....Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a red blood cell line. Simultaneously, this project aims to generate fundamental insights into mechanisms of human gene regulation. The technological and biological outcomes of this project will be of benefit for future gene editing applications.Read moreRead less
Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pa ....Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pathogenic behaviour and biomass production.Read moreRead less
Novel technology platform for gene delivery into intact cells. Delivery of DNA to cells is a crucial but highly inefficient process. This project will develop a way to manipulate the genetic code of cells efficiently and to easily generate stem cells from normal adult cells, thus avoiding controversial embryonic harvesting. This new technology will have potential benefits for research, agriculture and humans alike.
Tracking factor footprints to reveal the intricacy and control of translation initiation. Messenger ribonucleic acid (RNA) translation is required for all of life and knowledge of how it works is central to modern life sciences. This project will develop novel ways of studying translation, generating entirely new descriptions of its inner workings that may transform knowledge of gene function and its use in medical and biotechnological processes.
Discovery Early Career Researcher Award - Grant ID: DE190100116
Funder
Australian Research Council
Funding Amount
$415,737.00
Summary
Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically recons ....Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically reconstruct gene regulatory networks. These networks are the molecular basis for understanding human cells. This projects outcomes intend to include the first reference single-cell regulatory database and novel methods and software to predict individual cells. This project will contribute to advancing Australia's capabilities in single-cell, precision medicine, and big biological data analysis leading to significant scientific, societal and commercial benefits.Read moreRead less
Generating a targeted mutation resource in zebrafish. How do genes function to build organisms and how are they regulated to produce organs and tissues? Using a new technique to target specific genes in the genome of zebrafish, this project will determine how genes control formation of different tissues. The new gene "knockout" technology will fundamentally change our understanding of how genes work during development.
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less
Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms ....Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms of function remain poorly characterised and seldom considered. The expected outcome of better understanding mechanisms through which microRNAs work should provide significant benefit to safe and effective development of microRNAs for future agricultural or therapeutic application.Read moreRead less
Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102575
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Exploring new territory in climatic adaptation research: integrating molecular genetics with species' thermal tolerance limits. Predicting species' responses to environmental change requires mechanistic links between whole-organism physiological stress responses and underlying cellular mechanics. This project integrates cutting-edge methods in molecular and evolutionary genetics to probe species' responses to environmental change in the context of a warming environment.