Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identi ....Statistical Methods for Discovering Ribonucleic acids (RNAs) contributing to human diseases and phenotypes. Identifying the causative genetic factors involved in quantitative phenotypes and diseases is a major goal of biology in the 21st century and beyond. A crucial step towards this goal is identifying and classifying the functional non-protein-coding Ribonucleic acids (RNAs) encoded in the human genome. This project will make major contributions to international efforts in this area by identifying RNA molecules that contribute to quantitative phenotypes including susceptibility to disease. As such, it will directly benefit fundamental science via the discovery and classification of new molecules. Indirectly, it will lead to breakthroughs in biology, and consequently to major medical and pharmaceutical advances in the diagnosis and treatment of genetic disease.Read moreRead less
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 Mathematical Model of the Roles of Contraction and Oxygen in Human Wound Healing. Slow or impaired wound healing and excessive scarring associated with burns are both painful and costly. Moreover, the debilitating effect of chronic wounds can be expected to increase with the continuing aging of the population and the current rise in incidence of Type 2 diabetes. This project brings together a multidisciplinary team to develop a mathematical model of human wound healing and to drive the modelli ....A Mathematical Model of the Roles of Contraction and Oxygen in Human Wound Healing. Slow or impaired wound healing and excessive scarring associated with burns are both painful and costly. Moreover, the debilitating effect of chronic wounds can be expected to increase with the continuing aging of the population and the current rise in incidence of Type 2 diabetes. This project brings together a multidisciplinary team to develop a mathematical model of human wound healing and to drive the modelling to generate important breakthroughs at the level of basic science with implications for both experimentalists and clinicians.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
Mathematical models of cell migration in three-dimensional living tissues. This project aims to develop mathematical models of cell migration in crowded, living tissues. Existing models rely solely on stochastic simulations, and therefore provide no general mathematical insight into how properties of the crowding environment (obstacle shape, size, density) affect the migration of cells through that environment. This project will produce mathematical analysis, mathematical calculations and exact ....Mathematical models of cell migration in three-dimensional living tissues. This project aims to develop mathematical models of cell migration in crowded, living tissues. Existing models rely solely on stochastic simulations, and therefore provide no general mathematical insight into how properties of the crowding environment (obstacle shape, size, density) affect the migration of cells through that environment. This project will produce mathematical analysis, mathematical calculations and exact analytical tools that quantify how the crowding environment in three-dimensional living tissues affects the migration of cells within these tissues. Long term effects will be the translation of this new mathematical knowledge into decision support tools for researchers from the life sciences.Read moreRead less
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
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
Mathematical modelling of the dynamics of multi-layered biological tissues. The project intends to develop a mathematical model of the basic mechanisms that determine the self-organisation of cells into complex tissues during the development of the embryo. Tissue function requires a non-trivial tissue architecture often composed of multiple cell layers which exhibit a remarkable capacity for renewal and defect correction. A cardinal part of embryonic development involves robust shaping of multi- ....Mathematical modelling of the dynamics of multi-layered biological tissues. The project intends to develop a mathematical model of the basic mechanisms that determine the self-organisation of cells into complex tissues during the development of the embryo. Tissue function requires a non-trivial tissue architecture often composed of multiple cell layers which exhibit a remarkable capacity for renewal and defect correction. A cardinal part of embryonic development involves robust shaping of multi-layered tissue morphologies. The project plans to use mathematical models to determine how complex, three-dimensional structures arise from adaptive multicellular biomechanical interactions. It plans to develop a novel computational modelling framework to represent and analyse such systems, which may be applicable to a wide range of problems where tissue mechanics is a key factor such as bone remodelling and wound healing.Read moreRead less
How motor proteins contract the cell cortex and form a cell division ring. This project aims to develop a detailed physical model for motor proteins and filaments and, based on it, derive a fluid-type mean-field mathematical model, which will facilitate numerical simulations and lead to testable predictions. This study will also provide detailed quantitative information on how these processes can be controlled by modifying concentration and properties of structural and motor proteins. This has p ....How motor proteins contract the cell cortex and form a cell division ring. This project aims to develop a detailed physical model for motor proteins and filaments and, based on it, derive a fluid-type mean-field mathematical model, which will facilitate numerical simulations and lead to testable predictions. This study will also provide detailed quantitative information on how these processes can be controlled by modifying concentration and properties of structural and motor proteins. This has potential applications in tumour therapy, developmental biology and in the bioengineering of nanomaterials.Read moreRead less
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.Read moreRead less