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All-in-vitro engineering and single molecule analysis of protein complexes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to increase our understanding of the basic mechanisms of cell self-maintenance.
Discovering the role of pH in regulating mitochondrial biogenesis, so as to improve the design of preventative programs aimed at healthy ageing. Mitochondria are essential for life, and maintaining mitochondrial function plays an important role in preventing the progression of many age-related diseases. It has previously been shown that minimising the decrease in muscle pH that occurs during physical activity promotes greater improvements in mitochondrial function. The next step is to discover t ....Discovering the role of pH in regulating mitochondrial biogenesis, so as to improve the design of preventative programs aimed at healthy ageing. Mitochondria are essential for life, and maintaining mitochondrial function plays an important role in preventing the progression of many age-related diseases. It has previously been shown that minimising the decrease in muscle pH that occurs during physical activity promotes greater improvements in mitochondrial function. The next step is to discover the effects of altering pH on acute and chronic activity-induced changes in signalling proteins and genes that are involved in the regulation of skeletal muscle mitochondrial biogenesis. These experiments will significantly advance the knowledge base concerning factors regulating mitochondrial biogenesis, and will contribute to optimising the design of preventative programs aimed at healthy aging.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100929
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Stronger together: understanding antibiotic synergy on a molecular level. This project aims to use genomics-based approaches to answer fundamental questions about how antibiotic synergy works. Antibiotic combination therapy presents an opportunity to revive the use of antibiotics in otherwise resistant bacteria, yet currently there is little understanding of the molecular mechanisms underlying antibiotic synergy. Studies indicate that additional mechanisms of action (MOA) occur during synergist ....Stronger together: understanding antibiotic synergy on a molecular level. This project aims to use genomics-based approaches to answer fundamental questions about how antibiotic synergy works. Antibiotic combination therapy presents an opportunity to revive the use of antibiotics in otherwise resistant bacteria, yet currently there is little understanding of the molecular mechanisms underlying antibiotic synergy. Studies indicate that additional mechanisms of action (MOA) occur during synergistic killing beyond those of the original antibiotics. This project will identify genes involved in multiple synergistic treatments and determine how bacterial cells gain resistance. The synergy-specific MOA identified also represent an untapped reservoir of primary drug targets.Read moreRead less
A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
Defining the direct effects of exercise on arterial adaptation. Understanding the mechanisms responsible for the beneficial effects of exercise is fundamental to optimising the design of preventative programs aimed at healthy ageing. These experiments will contribute to our understanding of the direct effects of changes in blood flow and pressure during exercise on vascular adaptations in humans.
Australian Laureate Fellowships - Grant ID: FL210100071
Funder
Australian Research Council
Funding Amount
$3,246,000.00
Summary
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics wo ....“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics work, as models for early steps in the evolution of cellular life, and as a significant new platform for the production of proteins and fine chemicals. Outcomes and benefits include improved understanding of how to generate new antibiotics, and the development of new platforms for Australian biotechnology and biocommerce.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
Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the therm ....Sinusoidal voltage protocols for characterisation of ion channel kinetics. This project aims to implement an innovative approach to modelling ion channel behaviour that employs short, information-rich datasets and parameter inference. Using the hERG potassium channel as a test case, the project will show that this approach is more efficient than current methods and outperforms all published models in independent validations. The project aims to extend on initial implementation to probe the thermodynamics and pharmacology of ion channel gating. The anticipated outcomes are to grow fundamental knowledge of ion channel biophysics and ability to probe ion channel function in silico. The project will build on an emerging collaboration between international leaders in physiology, pharmacology, mathematics and computer modelling. The methodology and fundamental knowledge generated will significantly advance our understanding of the physiology and biophysics of ion channels, while the application of the method will have direct impact in the pharmaceutical industry and regulatory science.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130101393
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neurobiological mechanisms of decision under uncertainty. The purpose of this project is to understand the behavioural and brain mechanisms underlying decision under uncertainty. This research will uncover the effect that normal variation in brain networks has on choice and contribute to a better understanding of disorders linked to intolerance of uncertainty.
Discovery Early Career Researcher Award - Grant ID: DE220100185
Funder
Australian Research Council
Funding Amount
$438,712.00
Summary
Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The ....Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The role of thymic education in diversifying receptors 2) Whether gradual loss of thymic education affects receptor diversity 3) The molecular mechanisms underlying T cell strength. The project is essential for understanding how optimal T cell immunity is formed, critical if we wish to harness this to improve healthy aging.Read moreRead less