Theoretical Investigations Into Permeation Dynamics In Calcium- And Potassium-Selective Membrane Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$517,243.00
Summary
All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms at a molecular level is a fundamental problem in biology. There are many different types of ion channels, each type fulfilling a different role. We now know the exact atomic structures of several types of the proteins forming ion channels. Using this newly unveiled information, we propose to build exact physical models of two important classes of ion channels, namely, ....All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms at a molecular level is a fundamental problem in biology. There are many different types of ion channels, each type fulfilling a different role. We now know the exact atomic structures of several types of the proteins forming ion channels. Using this newly unveiled information, we propose to build exact physical models of two important classes of ion channels, namely, the calcium channels and potassium channels, using the technique known as 'homology' modelling. Then, making use of powerful supercomputers and the special computer programs we have devised, we propose to follow the motion of ions as they move through the channel and study how some chemical compounds or drugs interfere with the normal functioning of the channel. Specifically, we will attempt to understand how verapamil, which is used to treat irregular heart beats and high blood pressure, interact with the calcium channel. Once we fully understand how these channels work, we will be able to understand the causes of, and possibly find the cures for, many neurological and muscular disorders, such as cardiac arhythmia and hypertension.Read moreRead less
Theoretical Studies On The Dynamics Of Ion Permeation Across Membrane Channels
Funder
National Health and Medical Research Council
Funding Amount
$381,000.00
Summary
All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms at a molecular level is a fundamental problem in biology. There are many different types of ion channels, each type fulfilling a different role. We now know the exact atomic structures of several types of the proteins forming ion channels. Using this newly unveiled information, we propose to build exact physical models of many different types of ion channels. Then, ma ....All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms at a molecular level is a fundamental problem in biology. There are many different types of ion channels, each type fulfilling a different role. We now know the exact atomic structures of several types of the proteins forming ion channels. Using this newly unveiled information, we propose to build exact physical models of many different types of ion channels. Then, making use of powerful supercomputers, 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. Once we fully understand how these channels work, we will be able to understand the causes of, and possibly find the cures for, many neurological, muscular and renal disorders.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
Precipitation in shallow convection over the Southern Ocean. This project aims to quantify the amount of precipitation over the Southern Ocean and identify the key dynamical and microphysical processes that lead to its development. Large uncertainties exist in the frequency and intensity of precipitation, which limits the ability to model the coupled Southern Ocean climate system. Observations from the RV Investigator, an Australian marine research vessel, have revealed heavy precipitation event ....Precipitation in shallow convection over the Southern Ocean. This project aims to quantify the amount of precipitation over the Southern Ocean and identify the key dynamical and microphysical processes that lead to its development. Large uncertainties exist in the frequency and intensity of precipitation, which limits the ability to model the coupled Southern Ocean climate system. Observations from the RV Investigator, an Australian marine research vessel, have revealed heavy precipitation events within the shallow convection commonly found between fronts that have not been captured by either satellite observations or numerical models. This project will improve weather forecasts, including precipitation, and climate projections over the Southern Ocean and the adjoining Antarctic and the southern part of Australia.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102645
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The cause of the poleward shift of Earth's storm tracks and jet streams. Why do global climate models shift the atmospheric storm tracks and jet streams poleward in simulations of future climate? This project will determine the underlying causes of the most important circulation change that is projected to occur with increasing greenhouse gases, and will allow much more accurate regional climate projections.