Multiscale stochastic modelling of tumour robustness. This project will develop cutting-edge modelling methodologies of systems biology and innovative experimental techniques to investigate the principles of tumour initiation and progression, which lay at the heart of the national research priority Frontier Technologies for Building and Transforming Australian Industries. The primary outcome will be fundamental new paradigms explaining tumour initiation, cancer disease progression and the evolut ....Multiscale stochastic modelling of tumour robustness. This project will develop cutting-edge modelling methodologies of systems biology and innovative experimental techniques to investigate the principles of tumour initiation and progression, which lay at the heart of the national research priority Frontier Technologies for Building and Transforming Australian Industries. The primary outcome will be fundamental new paradigms explaining tumour initiation, cancer disease progression and the evolution of therapy resistance. The deep insights gained in this research have the potential for the optimal treatment strategies of cancer diseases, which is strongly relevant to promoting and maintaining good health for Australians.Read moreRead less
Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new labo ....Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new laboratory methods to develop better understanding of how these machines work, and how they malfunction in disease. This project will bring together four scientists with a unique combination of expertise and novel technologies to develop understanding of changes in structure of a large protein complex in different functional states.Read moreRead less
A mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a uni ....A mathematical model of calcium signalling in single cells and in multicellular systems. Calcium released from stores inside cells plays a vital signalling role in living organisms. It initiates cell division after fertilization, mediates communication and learning in the nervous system, causes contraction in the muscular walls of arteries and plays an important but as yet poorly understood role in the information processing that occurs in systems of coupled glial cells. We will construct a unified mathematical model of calcium signalling in multicellular systems, starting from the known processes in single cells, and use it to gain insight into the functioning and possible dysfunctioning of calcium-mediated intercellular communication.Read moreRead less
3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determinat ....Membrane Proteins within the Mouse Transcriptome- Annotation of their Organisation and Subcellular Localisation. A major issue in cell biology today is how distinct regions of the cell maintain their unique composition of proteins. The aim of this grant is to identify membrane proteins within the mouse genome and annotate their localisation within the cell. Our multi-discipline effort will combine extensive computational prediction strategies with focused cellular biology experimental determination. The underpinning experimental technology, termed reverse transfection arrays, allows for high-throughput assessment of cellular phenotype properties for individual proteins.Read moreRead less
New computational methods study on protein function prediction. The proposed research aims to develop new computational methods to solve one of the most important bioinformatics problems in the post-genome era. This project will expand the knowledge on protein sequence-structure-function relationship, provide new analysis methods and predict the functions of novel proteins. This project will strengthen Australia's reputation for research excellence.
Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will c ....Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will construct a set of physical models of biological ion channels, which will correctly replicate experimental observations. Such a theory will link the structure and function of an ion channel through the fundamental principles of physics.Read moreRead less
A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quanti ....A mathematical model relating neural activity to cerebral blood flow. An ageing population is increasingly prone to neurodegenerative disease and the associated mental impairment can severely disrupt the lives of both the sufferers and the carers. Non-invasive brain imaging techniques are used to both diagnose and supervise treatment of such disease, but at present a lack of understanding of the underlying physiology leaves these methods open to criticism. The construction of a detailed quantitative model of the basic processes underlying this imaging will enable precise interpretation of such brain scans and increase their usefulness both as a research and as a therapeutic tool.Read moreRead less
Economical and practical design and analysis of probabilistic distributed systems. Complex computing systems composed of communicating processes are
distributed over networks, and interact with embedded hardware
components. They routinely operate in probabilistic environments:
hardware components fail randomly, but at known rates; and tactical
randomisation resolves competition for resources. Effective
specification, development and analysis methods for these systems
is crucial, and probab ....Economical and practical design and analysis of probabilistic distributed systems. Complex computing systems composed of communicating processes are
distributed over networks, and interact with embedded hardware
components. They routinely operate in probabilistic environments:
hardware components fail randomly, but at known rates; and tactical
randomisation resolves competition for resources. Effective
specification, development and analysis methods for these systems
is crucial, and probability makes that particularly difficult.
The focus of this project is to develop new formal methods that are
economical and practical in use. Exploiting our recent advances in
probabilistic program semantics, we will add probability in a new
way to proven techniques in concurrency theory, including
refinement and hierarchical design.Read moreRead less
Algebraic reasoning for serialisability in probabilistic transaction systems. The ability to analyse complex systems is a vital part of the development of large-scale computer applications; a method that improves the quality of the analysis task would increase the competitiveness of the software industry, would attract future development work (in complex and intelligent systems) to Australia, and could contribute to national security.
The results of this project will have a direct influence ....Algebraic reasoning for serialisability in probabilistic transaction systems. The ability to analyse complex systems is a vital part of the development of large-scale computer applications; a method that improves the quality of the analysis task would increase the competitiveness of the software industry, would attract future development work (in complex and intelligent systems) to Australia, and could contribute to national security.
The results of this project will have a direct influence on currently available design tools; the fact that Australian institutions will be responsible for key theoretical results in this growing field will strengthen Australia's position worldwide as an international centre for computer science.Read moreRead less