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Investigation Of Biological Ion Channels: Theoretical Formulation, Computer Simulation And Experimental Verification
Funder
National Health and Medical Research Council
Funding Amount
$677,292.00
Summary
All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, undertanding their mechanisms at a molecular level is a fundamental problem in neurobiology. There are many different types of ion channels, each type fulfilling a different role. For the first time, a group of American scientists have determined the shape of one type of ion channels. Using this newly unveiled information, we propose to build a mathematical theory of ion channels. And then, making ....All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, undertanding their mechanisms at a molecular level is a fundamental problem in neurobiology. There are many different types of ion channels, each type fulfilling a different role. For the first time, a group of American scientists have determined the shape of one type of ion channels. Using this newly unveiled information, we propose to build a mathematical theory of ion channels. And then, making use of a powerful supercomputer, we propose to follow the motion of ions as they move through the channel, study how a channel can select only the correct type of ions to traverse it and determine how many ions a single channel is capable of processing per second. The predictions made by our theory and computer simulations will be checked experimentally. If the predictions and experimental findings do not agree, we will modify the theory and make new predictions.Read moreRead less
Uncovering The Molecular Mechanisms Behind Charcot-Marie-Tooth Disease
Funder
National Health and Medical Research Council
Funding Amount
$320,967.00
Summary
Charcot-Marie-Tooth disease (or CMT) is one of the most common disorders of the nervous system, affecting the normal function of the limbs and causing lifelong disabilities. There is currently no cure for CMT. The aim of this research is to develop a new model of CMT, which will allow us to uncover novel information about how the disease develops. This research will provide a better understanding of the disease and therefore provide valuable insight for the future generation of therapeutics.
Understanding The Link Between Mitochondrial Biogenesis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$421,055.00
Summary
As the predominate energy producers of our cells, mitochondria are implicated in a variety of diseases. To function properly, these dynamic organelles rely on protein components that regulate their structure and distribution throughout the cell. My work aims to expand our knowledge of the way these components control mitochondrial shape and trafficking. By understanding the correlation between mitochondrial morphology and function, we will gain insight into related diseases.
Molecular Energies and Non-Bonded Interactions. The development of new techniques that allow non-bonded chemical interactions to be modelled and predicted reliably and accurately will allow researchers in the chemical, and pharmaceutical sciences to predict the physical and chemical behaviour of moderately large molecular systems with an accuracy and efficiency that has not previously been possible. The software that will result will enable cost and time savings in molecular design within the m ....Molecular Energies and Non-Bonded Interactions. The development of new techniques that allow non-bonded chemical interactions to be modelled and predicted reliably and accurately will allow researchers in the chemical, and pharmaceutical sciences to predict the physical and chemical behaviour of moderately large molecular systems with an accuracy and efficiency that has not previously been possible. The software that will result will enable cost and time savings in molecular design within the medical and agricultural contexts.Read moreRead less
Biogenesis Of Respiratory Chain Complex I And Analysis Of Assembly Defects In Patients With Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Complex I of the mitochondrial respiratory chain is a large assembly of protein subunits that is involved in the main production of cellular energy. Complex I is found in intracellular compartments termed mitochondria. The predicament for Complex I is that in order for it to be built, it requires 38 different proteins that are made in one place in the cell to be imported into mitochondria and then somehow joined together with the 7 other subunits that are made by mitochondria. This is clearly a ....Complex I of the mitochondrial respiratory chain is a large assembly of protein subunits that is involved in the main production of cellular energy. Complex I is found in intracellular compartments termed mitochondria. The predicament for Complex I is that in order for it to be built, it requires 38 different proteins that are made in one place in the cell to be imported into mitochondria and then somehow joined together with the 7 other subunits that are made by mitochondria. This is clearly a complicated procedure and we have little information on how its assembly is achieved. We do know however that mistakes in the assembly of Complex I do happen. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others present later causing a range of degenerative diseases, particularly affecting brain, muscle and heart. The most common defect in these patients is a loss in the activity of Complex I. Interestingly it seems that in most cases, the defect is not due to a mutation in one or more of the Complex I subunits and so we believe that such defects arise form accessory proteins that are involved in the construction of Complex I. The aim of this proposal is to investigate how Complex I is assembled and to identify and characterise accessory proteins. We will also analyse assembly defects by studying skin fibroblasts from patients. This work will aid in our understanding of not only how protein complexes are built, but how defects in their assembly can cause disease. This will not only be informative to families of affected individuals but may aid in future diagnosis and prevention of mitochondrial disease.Read moreRead less
Creating new stochastic models to understand the evolution of gene families. This project aims to extend stochastic modelling techniques in order to develop mathematically rigorous and biologically relevant models for the evolution of gene families. The project expects to model evolutionary processes such as gene retention, duplication and loss, and the generation of new gene functions. The duplication and subsequent re-purposing of genes is thought to be a key mechanism for generating evolution ....Creating new stochastic models to understand the evolution of gene families. This project aims to extend stochastic modelling techniques in order to develop mathematically rigorous and biologically relevant models for the evolution of gene families. The project expects to model evolutionary processes such as gene retention, duplication and loss, and the generation of new gene functions. The duplication and subsequent re-purposing of genes is thought to be a key mechanism for generating evolutionary novelty. By applying these models to genome data, the project expects to be able to quantify the importance of these different evolutionary mechanisms. The project will strengthen collaborative links between researchers in stochastic modelling and molecular evolutionary biology.Read moreRead less
Stochastic modelling of spatiotemporal nonlinear diffusion processes with multifractal characteristics. This research is relevant to solute transport and plume evolution in heterogeneous media. Detailed modelling of these processes is computer-intensive, while the diffusion models of this project offer a more economical alternative. Our study will also benefit the research on the salinity problem. Excessive demand for irrigation water to support agricultural production has stretched freshwater a ....Stochastic modelling of spatiotemporal nonlinear diffusion processes with multifractal characteristics. This research is relevant to solute transport and plume evolution in heterogeneous media. Detailed modelling of these processes is computer-intensive, while the diffusion models of this project offer a more economical alternative. Our study will also benefit the research on the salinity problem. Excessive demand for irrigation water to support agricultural production has stretched freshwater aquifers beyond their long-term yield. Large areas of land have been lost to saltwater intrusion. This proposal will provide suitable tools to predict the level and movement of saltwater in the aquifers. Application to the development of management strategies would bring direct benefit to coastal areas where salinity is a sustainability issue.Read moreRead less
Stochastic modelling and analysis of spatio-temporal processes with fractal characteristics. Interest has grown in recent years on the derivation of fractal models to represent certain physical phenomena such as diffusion and transport in porous media, oceanic and atmospheric turbulence, climatology, etc. This project focuses on the phenomenon of diffusion on domains with multifractal geometry. Recent advances in harmonic analysis on fractals and our own development of fractional generalized ran ....Stochastic modelling and analysis of spatio-temporal processes with fractal characteristics. Interest has grown in recent years on the derivation of fractal models to represent certain physical phenomena such as diffusion and transport in porous media, oceanic and atmospheric turbulence, climatology, etc. This project focuses on the phenomenon of diffusion on domains with multifractal geometry. Recent advances in harmonic analysis on fractals and our own development of fractional generalized random fields allow us to formulate a comprehensive program to tackle some key problems including modeling, processing and statistical estimation of fractional diffusion. Advances made in this program will in turn benefit the developments in related scientific fields.Read moreRead less