Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional character ....Characterisation of two-pore domain potassium channels: structure-function studies of the M1-P1 loops of TASK channels. TWIK-related Acid Sensitive K+ (TASK) channels are members of the novel class of two-pore domain potassium channel family. They are potently inhibited by local anaesthetics and have been implicated as having important roles in many pathophysiological conditions such as heart arrythmias, stroke, epilepsy, breast and other cancers. The in depth structural and functional characterisation of this class of potassium channels is of great importance as they are interesting targets for new therapeutic developments. Advancement of knowledge in the structure and function of these channels will underpin drug targeting that will aid preventative healthcare, allowing Australians to age well and age productively.Read moreRead less
Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that tr ....Molecular Mechanisms of Biochemical Regulation: Neutron and X-ray Scattering Studies. This project will develop and use novel neutron and x-ray scattering methods to study the molecular mechanisms by which nature regulates biochemical processes. Healthy function requires cells to tightly control and coordinate a myriad of molecular activities. My research focuses on a set of interdependent molecular networks inside cells whose behavior is controlled by the so-called 'second messengers' that translate external signals into the right cellular responses. The proposed experiments will provide a unique structural framework by which we can understand how these signals are transmitted. Such knowledge is an important foundation for advances in biomedical research and biotechnology applications.Read moreRead less
Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcom ....Molecular mechanisms of two-component signal transduction in bacteria. The focus of this research is on the protein complexes that transmit signals in bacteria to elicit the desired responses to environmental stimuli. Like many dynamic processes in cells, signaling requires proteins that are flexible and hence resistant to high-resolution structural analysis using crystallography. We will make use of new research infrastructure at the Australian synchrotron and OPAL research reactor to overcome the challenges of flexibility in these systems. The proteins we will study are not found in humans, and hence our research will provide important structural data on potential targets for the design of novel antibiotics to fight bacterial infection.Read moreRead less
Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales ....Hierarchical modeling of protein interactions. Protein interactions play a central role in function and structural organization of cells. Their elucidation is essential for a better understanding of many cellular processes from signal transduction to enzyme inhibition. The aim of this project is to utilize the unprecedented powers of current supercomputers in developing a hierarchical model of protein interactions. The method combines Brownian dynamics at large distances and long time scales with molecular dynamics at small distances and shorter times. Applications to both membrane proteins (blocking of ion channels by toxins and drugs) and globular proteins (ligand binding to receptors and protein association) will be considered.Read moreRead less