Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathway ....Iron, ferroptosis and the biology of ageing. This project aims to determine how and when regulation of iron is lost. Failing iron metabolism during life may dictate the rate of ageing by driving a newly discovered cell death program. Combining biology, chemistry and physics, this collaborative project aims to transform the understanding of the fundamental mechanisms of biological ageing. Anticipated outcomes include new assays for measuring iron in biology and identification of potential pathways that regulate death signaling and lifespan. Outcomes will benefit life sciences and biotechnology industries.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100080
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Examining lipid transport by direct visualisation and quantification. This project aims to investigate the least understood aspect of plasma triglyceride metabolism; mechanisms of transport across capillary endothelial cells. This transport regulates plasma triglyceride levels, which are an important factor in determining risk for coronary diseases. An improved understanding of these mechanisms will lead in the long term to better understandings of both heart failure and atherosclerotic heart di ....Examining lipid transport by direct visualisation and quantification. This project aims to investigate the least understood aspect of plasma triglyceride metabolism; mechanisms of transport across capillary endothelial cells. This transport regulates plasma triglyceride levels, which are an important factor in determining risk for coronary diseases. An improved understanding of these mechanisms will lead in the long term to better understandings of both heart failure and atherosclerotic heart diseases.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100058
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Molecular reporters for measuring proteostasis capacity in cells. This project aims to develop fluorescent dyes to report on the change in unfolded protein load, which reflects the proteostasis status in real time in cells under stress conditions. Proteostasis is a housekeeping process cells undertake to maintain the proper folding and functions of proteins. Perturbation of proteostasis has been linked to neurodegenerative diseases, but chemical probes cannot measure the proteostasis capacity in ....Molecular reporters for measuring proteostasis capacity in cells. This project aims to develop fluorescent dyes to report on the change in unfolded protein load, which reflects the proteostasis status in real time in cells under stress conditions. Proteostasis is a housekeeping process cells undertake to maintain the proper folding and functions of proteins. Perturbation of proteostasis has been linked to neurodegenerative diseases, but chemical probes cannot measure the proteostasis capacity in cells. Intended outcomes include a mechanistic understanding of the relationship between protein misfolding, aggregation and proteostasis. This is expected to ultimately benefit the diagnosis of protein folding diseases, including dementia, and improve the quality of life.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100118
Funder
Australian Research Council
Funding Amount
$370,000.00
Summary
Regional flow cytometry facility. Flow cytometry facility: This project will establish a flow cytometry facility, featuring the latest technology in two separate complementary machines, one an analyser the other a cell sorter. This facility will provide urgently needed replacement of aging infrastructure, and will also provide researchers with new capabilities that will lead to substantial research advances across many diverse fields.
Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu ho ....Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu homeostasis is maintained or perturbed under various stresses. In the future, this work is expected to form the basis of studies of brain Cu pools in neurodegenerative diseases.Read moreRead less
Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100584
Funder
Australian Research Council
Funding Amount
$424,636.00
Summary
DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into ....DNA Replication Stress: Characterizing ground zero for genomic instability. The overarching goal of this research is to gain insights into key underlying molecular causes of, and responses to, DNA replication stress - one of the most fundamental biological processes enabling life as we know it. I will use advanced interdisciplinary imaging techniques to directly visualize DNA replication stress structures within cells in order to better understand how cells stop this stress from progressing into DNA damage. Insights into these processes will have the potential to improve preventative and therapeutic approaches to diseases such as cancer and neurodegeneration. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less
Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-m ....Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-molecule biophysical techniques has begun to challenge many aspects of the elegant textbook view of replisome function. This approach is expected to reveal how synthesis of the two DNA strands in different directions at the same time is coupled together and how timing mechanisms work.Read moreRead less