Mathematical models of 4D multicellular spheroids. Mathematical models have a long, successful history of providing biological insight, and new mathematical models must be developed to keep pace with emerging technologies. Modern experimental procedures involve studying 3D multicellular spheroids with fluorescent labels to show both the location of cells and the cell cycle progression. This 4D data (3D spatial information + cell cycle time) provides vast information. No mathematical models ha ....Mathematical models of 4D multicellular spheroids. Mathematical models have a long, successful history of providing biological insight, and new mathematical models must be developed to keep pace with emerging technologies. Modern experimental procedures involve studying 3D multicellular spheroids with fluorescent labels to show both the location of cells and the cell cycle progression. This 4D data (3D spatial information + cell cycle time) provides vast information. No mathematical models have been specifically developed to interpret/predict 4D spheroids. This project will deliver the first high-fidelity mathematical models to interpret/predict 4D spheroid experiments in real time, providing quantitative insight into innate mechanisms and responses to various intervention treatments. Read moreRead less
The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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Discovery Early Career Researcher Award - Grant ID: DE200101791
Funder
Australian Research Council
Funding Amount
$427,082.00
Summary
Mathematically optimal R&D for coral reef conservation. This project aims to develop mathematical methodologies for optimising Research & Development (R&D) of technologies that will secure complex and uncertain ecosystems into the future. Current conventional management approaches will not prevent the degradation of threatened ecosystems like the Great Barrier Reef, so new technologies are needed. The biggest challenge in choosing these technologies is the long delay between development and depl ....Mathematically optimal R&D for coral reef conservation. This project aims to develop mathematical methodologies for optimising Research & Development (R&D) of technologies that will secure complex and uncertain ecosystems into the future. Current conventional management approaches will not prevent the degradation of threatened ecosystems like the Great Barrier Reef, so new technologies are needed. The biggest challenge in choosing these technologies is the long delay between development and deployment, in which time ecosystem function may collapse and complex, dynamic ecological and social systems will change. The mathematical methods and theory developed will inform a Great Barrier Reef case study, and will be ready for rapid application to other ecosystems as the urgent need arises.Read moreRead less
How can cultural innovations trigger the emergence of new diseases? This project aims to develop new mathematical and computational models to examine whether cultural innovations creates conditions for the emergence of new diseases. It will combine elements of microbial evolution and cultural evolution to advance a new modelling framework to consider their joint dynamics. The expected outcome is an enhanced understanding of how human behaviour influences the emergence of infections. This will br ....How can cultural innovations trigger the emergence of new diseases? This project aims to develop new mathematical and computational models to examine whether cultural innovations creates conditions for the emergence of new diseases. It will combine elements of microbial evolution and cultural evolution to advance a new modelling framework to consider their joint dynamics. The expected outcome is an enhanced understanding of how human behaviour influences the emergence of infections. This will bring benefits of computational models for broad use in understanding complex population processes, and training to maintain mathematical and computational skills in the Australian workforce.
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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: DE210101344
Funder
Australian Research Council
Funding Amount
$364,981.00
Summary
Advancing genomic-driven infectious diseases modelling. Emerging infectious diseases and antimicrobial resistance are among the greatest threats to Australian health and agriculture, and current surveillance tools may fail to detect and mitigate infectious disease outbreaks in real time. This project will develop advanced phylodynamic methods (i.e., mathematical models of infectious disease transmission and pathogen evolution) to enable real-time surveillance of infectious disease outbreaks as t ....Advancing genomic-driven infectious diseases modelling. Emerging infectious diseases and antimicrobial resistance are among the greatest threats to Australian health and agriculture, and current surveillance tools may fail to detect and mitigate infectious disease outbreaks in real time. This project will develop advanced phylodynamic methods (i.e., mathematical models of infectious disease transmission and pathogen evolution) to enable real-time surveillance of infectious disease outbreaks as they emerge and monitor levels of drug resistance.Read moreRead less
Optimising progress towards elimination of malaria. The project aims to advance mathematical knowledge by developing novel tools appropriate for modelling disease elimination. We will apply these new mathematical tools to the significant problem of malaria elimination in Vietnam. The expected outcomes are new tools for modelling disease elimination on a fine spatial resolution with heterogeneities in individual patient characteristics, calibrating models to household level data on disease transm ....Optimising progress towards elimination of malaria. The project aims to advance mathematical knowledge by developing novel tools appropriate for modelling disease elimination. We will apply these new mathematical tools to the significant problem of malaria elimination in Vietnam. The expected outcomes are new tools for modelling disease elimination on a fine spatial resolution with heterogeneities in individual patient characteristics, calibrating models to household level data on disease transmission and designing intervention strategies for maximum effect on disease transmission. The innovative combination of modelling, inference and optimisation ensures that the mathematical methods developed will be broadly applicable to modelling elimination strategies for other infectious diseases.
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A Novel Geometric Approach to Shocks in Reaction-Nonlinear Diffusion Models. Reaction-nonlinear diffusion models play a vital role in the study of cell migration and population dynamics. However, the presence of aggregation, or backward diffusion, leads to the formation of shock waves - distinct, sharp interfaces between different populations of densities of cells - and the breakdown of the model. This project will develop new geometric methods to explain the formation and temporal evolution of ....A Novel Geometric Approach to Shocks in Reaction-Nonlinear Diffusion Models. Reaction-nonlinear diffusion models play a vital role in the study of cell migration and population dynamics. However, the presence of aggregation, or backward diffusion, leads to the formation of shock waves - distinct, sharp interfaces between different populations of densities of cells - and the breakdown of the model. This project will develop new geometric methods to explain the formation and temporal evolution of these shock waves, while simultaneously unifying existing regularisation techniques under a single, geometric banner. It will devise innovative tools in singular perturbation theory and stability analysis that will identify key parameters in the creation of shock waves, as well as their dynamic behaviour.Read moreRead less
Root-to-shoot: modeling the salt stress response of a plant vascular system. Salt and drought are the two major abiotic stresses affecting crop plant health, growth and development. We aim to understand salt and water transport in plants and the physiological effects of soil salinity. Using biophysical models, we will quantify the movement of salt through plant organs, tissues and cells, from root to leaf. We aim to answer the question of how salt moves across the different tissues and major org ....Root-to-shoot: modeling the salt stress response of a plant vascular system. Salt and drought are the two major abiotic stresses affecting crop plant health, growth and development. We aim to understand salt and water transport in plants and the physiological effects of soil salinity. Using biophysical models, we will quantify the movement of salt through plant organs, tissues and cells, from root to leaf. We aim to answer the question of how salt moves across the different tissues and major organs, how salt accumulates in root, leaf and shoot cells, and how movement and accumulation is controlled by the diversity of transport mechanisms operating in plants. We aim to quantify tissue tolerance, osmotic tolerance and ionic tolerance and discover new mechanisms by which plants can stave off the effect of salt stress.Read moreRead less
The mathematics of stochastic transport and signalling in cells. The project aims to develop new stochastic mathematical models of the dynamics of protein transport and cell signalling. The mathematics will link macro scale biological observations to micro scale molecular movements to characterise the relative role that different components and processes play. Expected outcomes are robust mathematical analyses of the transient dynamics of closed, finite capacity queueing networks and biological ....The mathematics of stochastic transport and signalling in cells. The project aims to develop new stochastic mathematical models of the dynamics of protein transport and cell signalling. The mathematics will link macro scale biological observations to micro scale molecular movements to characterise the relative role that different components and processes play. Expected outcomes are robust mathematical analyses of the transient dynamics of closed, finite capacity queueing networks and biological insight into the major control mechanisms in cellular insulin signalling. The project should provide significant benefits via the delivery of new mathematical tools and analysis for stochastic networks, impacting our understanding of metabolic transport, and providing interdisciplinary research training.Read moreRead less