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
Biomathematical Analysis Of Cell Invasion: Migration Of Neural Crest Cells To Form The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$449,484.00
Summary
Extending scientific studies to a mathematical level is the way to produce deep understanding and control. Mathematics has been applied less to biology, particularly the biology of development, than to other branches of science, no doubt due to the innate complexity and technical difficulties of seeing and measuring what is actually going on. Labelling, imaging and computational tools to visualise biological processes are only now becoming available. To build our bodies during embryonic developm ....Extending scientific studies to a mathematical level is the way to produce deep understanding and control. Mathematics has been applied less to biology, particularly the biology of development, than to other branches of science, no doubt due to the innate complexity and technical difficulties of seeing and measuring what is actually going on. Labelling, imaging and computational tools to visualise biological processes are only now becoming available. To build our bodies during embryonic development, cells must move; this is called cell migration. The same process occurs throughout life in wound repair. Uncontrolled migration is the hallmark of malignant cancers, where it is called invasion. The molecular mechanisms in cells that allow them to move are just beginning to be understood. However, the big questions determining the general rules of migration are more difficult to approach. Here are some examples of such questions. When to migrate? Where to migrate to? Which pathways? How many cells to migrate? How far? How fast? How to stop? Such simple questions are still unanswered. We are pioneering a novel and unique approach combining imaging of real cells migrating in real tissues (digital time-lapse movies) with mathematical modelling to understand the driving forces of cell migration-invasion. This technology is here applied to a particular example of cell migration where precursor nerve cells migrate all the way along the length of the gastro-intestinal tract in early development. This process gives rise to fatal birth defects associated with migration failure. The development of the nervous system in the gut has features in common with all other migrations and invasions, normal and pathological. A much more profound knowledge of the big picture of the developmentally and clinically crucial process of cell migration-invasion will emerge from this marriage of biological experimentation and mathematical modelling.Read moreRead less
Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
Dissecting the mitochondrial pathway of apoptotic cell death. This research aims to identify each step in cell death regulation by the Bcl-2 family of proteins. Each step is a potential target for drugs that may help cancer cells die, or that may help normal cells such as heart and brain cells recover from damage.
Computational enzymology: exploring the free energy landscape of enzymatic catalysis. Most biochemical reactions depend on enzyme catalysis and understanding how enzymes work at the molecular level remains a central question. This project will develop a suite of computational models to study the mechanisms of enzyme-catalysed reactions and such knowledge holds promise for technological benefits in the form of new drugs and novel catalysts.
Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project ....Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project outcomes are intended to lead to significant advances in membrane protein structure determination and will have a substantial impact on future research in the pharmaceutical industry.Read moreRead less
Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting p ....Protein structure controls light harvesting in photosynthetic light algae. The strange phenomena of quantum mechanics were not expected to play a direct role in life, however, it appears that quantum effects may be important in the efficient capture of sunlight for photosynthesis. The conditions for the emergence of quantum phenomena appear to be set by the structures of proteins. The aim of this project is to relate protein structure to the emergence of quantum effects in the light harvesting proteins of marine algae. Understanding the link between structure and quantum effects could improve our knowledge of how nature achieves its remarkable efficiency in utilising the energy from the sun. This is likely to foster new technologies that improve the efficiency of solar energy systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100090
Funder
Australian Research Council
Funding Amount
$640,000.00
Summary
A centre for structural cryo-electron microscopy. This equipment will use powerful microscopes to visualise the shape of proteins. The data generated in the facility will provide fundamental insight into how large complex proteins govern life-and-death events in biology. These data will be important for scientists to develop new approaches to control aberrant protein function in disease.