The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper a ....The impact of copper on protein turnover. This project aims to elaborate a novel discovery by the research team, that a conserved copper-binding site in a group of conserved conjugating enzymes promotes ubiquitination of a range of essential proteins leading to their rapid degradation, which might be a means of maintaining copper homeostasis. This project will employ a range of integrated physicochemical, biochemical and cell biology approaches to illuminate the molecular nature of this copper action on the enzyme and its partners. Expected outcomes include an analytical understanding of the molecular mechanisms of this process, and enhanced interdisciplinary collaboration between experts. Potential benefits include new strategies to intervene in copper-related disorders of aging.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101236
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of ho ....Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of how specific modifications modulate protein and cellular function. Significant benefits of this interdisciplinary project include access to a new class of molecules for basic research that may also find use for cell engineering applications within the growing biotechnology sector in Australia.Read moreRead less
High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. Wit ....High-throughput single-molecule directed evolution. DNA polymerases are essential enzymes in many biotechnological tools, including DNA sequencing and PCR tests. However, existing DNA polymerases have limitations, resulting in inaccuracies and inefficiencies. Existing methods to improve polymerases lack sensitivity to screen for subtle, yet pivotal traits. This project aims to overcome this limitation by developing a new single-molecule directed-evolution system to evolve better polymerases. With this new technology we aim to identify DNA polymerases with improved performance that benefit biotechnological applications. Additionally, these single-molecule directed-evolution methods will benefit the wider scientific community and lay the foundation for further advances in directed evolution.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101536
Funder
Australian Research Council
Funding Amount
$473,824.00
Summary
How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the mole ....How does heme regulate blood vessel formation in the brain? There are more than 600 kilometres of blood vessels in the brain, all of which are lined by tightly packed cells that protect the brain from toxins. My research aims to investigate how these blood vessels are formed. This project expects to reveal the role that a critical signalling molecule called heme plays in this fundamental biological process. I will use cutting-edge structural biology and biophysical techniques to uncover the molecular mechanisms that allow heme to enter cells and regulate blood vessel growth in the brain. The outcomes of this research will enhance our understanding of the brain’s core infrastructure and will contribute to an understanding of how cerebral blood vessels grow and maintain integrity. Read moreRead less
A peptide platform to fight pests threatening global food security. This project aims to develop a platform technology for the efficient design of new crop protection agents based on peptides to protect Australia’s food security. It will be first applied against the highly destructive fall armyworm, currently spreading alarmingly in Australia. The project is significant because insect pests cause huge economic and environmental impacts. Peptides are a new generation of crop protection agents tha ....A peptide platform to fight pests threatening global food security. This project aims to develop a platform technology for the efficient design of new crop protection agents based on peptides to protect Australia’s food security. It will be first applied against the highly destructive fall armyworm, currently spreading alarmingly in Australia. The project is significant because insect pests cause huge economic and environmental impacts. Peptides are a new generation of crop protection agents that are potentially more effective and sustainable than chemical pesticides. Expected outcomes are a new rapid response technology and associated lead molecules to protect against current and emerging pests. Major benefits are increased food security, improved crop yields and a more sustainable agriculture industry. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100780
Funder
Australian Research Council
Funding Amount
$455,237.00
Summary
Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecul ....Functional and structural dissection of the human replisome. This project aims to develop technology to visualise the structure and enzymatic activities of the human replisome, the multiprotein assembly that copies DNA before cell division. A combination of novel single-molecule and state-of-the-art cryo-electron microscopy will be used to define how the human replisome coordinates DNA synthesis during times of replication stress. Key outcomes of this project include development of novel molecular visualisation technologies, leading to the first molecular description of dynamic processes used by the human replisome. Benefits include improved understanding of a fundamental biological process that often malfunctions in cancers, development of novel methodology, and interdisciplinary training.Read moreRead less