New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific detail ....New data-driven mathematical models of collective cell motion. Cancer and chronic wounds are a national, and indeed, international health problem set to worsen as our population ages. Predictive and interpretive tools are required to improve our understanding of collective cell migration in relation to cancer and chronic wounds. This project will produce new validated mathematical tools for predicting collective cell migration in a general framework that can deal with application-specific details, such as the role of cell shape and cell size. Although cell shape and size are known to affect collective cell migration, standard mathematical models ignore these details. This project will produce new predictive mathematical modelling tools that are validated by new experimental data. Read moreRead less
Modelling cell invasion incorporating the epithelial to mesenchymal transition: Exploring therapies to control wound healing and cancer progression. Cancer and wounds are closely related, commonly lethal, diseases. Both require cell growth and invasion. This project will apply experimental measurements to create new mathematical models of cancer and wounds; models that will inform new targets and strategies for the treatment of these deadly diseases.
Human skin equivalent constructs: enhanced culturing and application of laboratory-grown skin through mathematical modelling and in silico experimentation. Laboratory-grown human skin equivalent constructs, given social and legislative imperatives, will be critical for advances in novel treatment protocol definitions for wound repair, dermatogical screening of pharmacueticals and fundamental studies of skin diseases.
In silico studies undertaken in this project will make a significant contrib ....Human skin equivalent constructs: enhanced culturing and application of laboratory-grown skin through mathematical modelling and in silico experimentation. Laboratory-grown human skin equivalent constructs, given social and legislative imperatives, will be critical for advances in novel treatment protocol definitions for wound repair, dermatogical screening of pharmacueticals and fundamental studies of skin diseases.
In silico studies undertaken in this project will make a significant contribution to the effectiveness of the application of human skin constructs, by delivering new and deeper insights into the interplay between dependent processes that regulate the behaviour of skin, in vivo or ex vivo. The models and the researchers associated with this project will drive innovative studies in medical science over the next decade.Read moreRead less
A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provid ....A new hierarchy of mathematical models to quantify the role of ghrelin during cell invasion. Ghrelin is a recently-discovered growth factor that regulates appetite and promotes tumour growth by enhancing cell invasion. The mechanisms by which ghrelin enhances cell invasion are, at present, unknown. This innovative project will develop a new hierarchy of multiscale mathematical models that will be used to quantify how ghrelin modulates cell behaviour (motility, proliferation and death) and provide insight into the precise details of how ghrelin promotes cell invasion. This project will demonstrate the potential for ghrelin-based strategies to control cell invasion. By linking appetite regulation and tumour growth, the outcomes from this project will inform Australian health policy in this important area.Read moreRead less
Inter-fragmentary movement in callus formation in the early phase of fracture healing. Computational models of the early phase of bone fracture healing can provide the means to characterise the biochemical factors that control this process, and subsequently influence successful healing outcomes, with or without surgical intervention. This unique approach, incorporating soft tissue and fixation device contributions to fracture healing, will ultimately provide a sound basis for clinical decision-m ....Inter-fragmentary movement in callus formation in the early phase of fracture healing. Computational models of the early phase of bone fracture healing can provide the means to characterise the biochemical factors that control this process, and subsequently influence successful healing outcomes, with or without surgical intervention. This unique approach, incorporating soft tissue and fixation device contributions to fracture healing, will ultimately provide a sound basis for clinical decision-making, implant design and future experimental studies. Facilitating treatment optimisation, the outcomes of this project will create opportunities to reduce healthcare costs, physical impairment, and productivity losses for the 150,000 Australian patients hospitalised annually with fractures.Read moreRead less
Motor Unit Numbers Estimation (MUNE) using Bayesian statistical methodology for monitoring of progression of neuromuscular diseases. A means of objectively measuring the pathology of a neuromuscular disease involving motor unit loss, such as motor neuron disease, is much needed. This will be achieved by using newly developed electrophysiological techniques and developing new Bayesian statistical methodology to determine the number of motor units that supply a muscle. Our innovations will reliabl ....Motor Unit Numbers Estimation (MUNE) using Bayesian statistical methodology for monitoring of progression of neuromuscular diseases. A means of objectively measuring the pathology of a neuromuscular disease involving motor unit loss, such as motor neuron disease, is much needed. This will be achieved by using newly developed electrophysiological techniques and developing new Bayesian statistical methodology to determine the number of motor units that supply a muscle. Our innovations will reliably determine the number of motor units that supply a muscle in both normal subjects and in diseased patients with loss of motor nerves. This will enable the monitoring of disease progression. An outcome will be a software package that can be used with standard electrophysiology machines.Read moreRead less
Determination of benchmarking parameters for assessing the mechanical robustness of articular cartilage: a joint mathematical and experimental investigation. Osteoarthritis associated with the deterioration of the articular cartilage affects about 12% of Australian adults. This project will use an integrated approach combining novel mathematical modelling and an extensive experimental program to establish critical mechanical parameters, in particular, the fracture toughness of articular cartilag ....Determination of benchmarking parameters for assessing the mechanical robustness of articular cartilage: a joint mathematical and experimental investigation. Osteoarthritis associated with the deterioration of the articular cartilage affects about 12% of Australian adults. This project will use an integrated approach combining novel mathematical modelling and an extensive experimental program to establish critical mechanical parameters, in particular, the fracture toughness of articular cartilage and will incorporate the unique structure of the dissimilar layers in articular cartilage. It will be used to study how these resist the propagation of an initiated crack and will offer significant insight into the desirable fracture properties of any replacement material for articular cartilage and will provide a basis for assessing replacement biomaterials.Read moreRead less
A new theory for retinotectal map formation. How brains become wired up during development is a question of
importance to both biology and computing. In this project we adopt a
novel computational approach to understanding the development of
topographic maps, a wiring pattern that is ubiquitous in biological
nervous systems. This project will build capacity for research in
computational neuroscience in Australia. It may also lead to
technological benefits such as new ideas for the design o ....A new theory for retinotectal map formation. How brains become wired up during development is a question of
importance to both biology and computing. In this project we adopt a
novel computational approach to understanding the development of
topographic maps, a wiring pattern that is ubiquitous in biological
nervous systems. This project will build capacity for research in
computational neuroscience in Australia. It may also lead to
technological benefits such as new ideas for the design of self-wiring
computing devices, and new insights into
the causes of wiring defects both during normal development and
rewiring after injury.
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Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell sign ....Spatio-temporal modelling of Ras dependent MAP kinase activation. This project is at the heart of the national research priority 'Frontier Technologies for Building and Transforming Australian Industries'. Using cutting edge methods and techniques of systems biology, coupled with innovative experimental molecular cell biology we will construct and simulate mathematical models of the EGF-regulated MAP kinase pathway. The project will yield new insights into the fundamental mechanisms of cell signal transduction that drive cell division, differentiation and transformation and may enable the design of new anticancer therapies. Importantly, the modelling and simulation methods developed in the project will have a general applicability to other complex systems such as sustainable ecological systems.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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