Mechanism Of Anoxic Iron Acquisition In Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$536,280.00
Summary
All organisms require iron for their survival, including all bacterial species. Bacterial pathogens growing in anaerobic environments, such as in our gut, gum, or tissue, sequester iron through the divalent iron transporter FeoB. We aim to divulge the mechanism of iron transport through FeoB by structural and functional studies, and thus provide a scaffold for a non-conventional antimicrobial target.
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less
Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Tra ....Promoting active travel and public transport for a post-pandemic world. In many major cities, COVID-19 stimulated the provision of open streets, pop up bike lanes and widened pedestrian access, prompting unprecedented increases cycling and walking. While this type of infrastructure has always been supported by urban planners and designers, the pandemic has served as a vital inflection point, enabling cities to pursue long-term sustainable transport initiatives, including investment in Active Travel (AT). There is an opportunity to promote AT as part of an integrated transport strategy, and to develop tools for the robust evaluation of AT impacts to inform future investment strategies. This proposal will provide our partner organisation Transport for New South Wales (with the knowledge required to achieve this.
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Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning ....Integrating Attribute Decision Heuristics into Travel Choice Models that accommodate Risk Attitude and Perceptual Conditioning. This proposal has the specific objective of integrating two disconnected literatures that are having a major influence on the behavioural and statistical performance of discrete choice models in travel choice modelling. These fields are attribute processing strategies and the conditioning of the marginal utility of attributes by risk attitude and perceptual conditioning. These two major developments have not been jointly integrated into a behaviourally richer representation of choice making. Given the encouraging evidence from both literatures, the research will determine more precisely the benefits in terms of improved estimates of willingness to pay for specific attributes and also increased predictive power. Read moreRead less
Development Of Iron Complexes For The Treatment Of FriedreichÍs Ataxia & The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$616,143.00
Summary
Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal c ....Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal could lead to novel therapies for FARead moreRead less
Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, a ....Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, and evaluate focussing of waves by complex currents on the continental shelf to help improve wave forecasting in coastal waters. The HF radar will be used to experimentally test current theories of wind wave spreading.Read moreRead less
Shape adaptive structures with built-in compact smart material based actuators. Primary Australian aerospace manufacturers are sub-contractors and constantly compete in the global market. Their products are primarily control surfaces, e.g., Boeing 757 and 777 rudders, 737 Krueger flaps. In light of the development of the hingeless control surfaces (HCS) in the smart aircraft wing program in the USA, the economic benefits of this project are very high because (a) it will address the key technolo ....Shape adaptive structures with built-in compact smart material based actuators. Primary Australian aerospace manufacturers are sub-contractors and constantly compete in the global market. Their products are primarily control surfaces, e.g., Boeing 757 and 777 rudders, 737 Krueger flaps. In light of the development of the hingeless control surfaces (HCS) in the smart aircraft wing program in the USA, the economic benefits of this project are very high because (a) it will address the key technological issue identified in the HCS program; and (b) it will enhance Australian manufacturers¡¯ technological standing and input in the design and manufacturing of next generation HCS by providing highly trained people with world-leading niche technology.Read moreRead less
Active shape control of large thin-walled structures using ferroelectric single crystals. Ferroelectric single crystals were invented 5 years ago, and they possess many superior properties compared to conventional piezoelectric materials, particularly the induced strain up to 1.5%, an order higher than conventional materials. This project aims to poineer the application of these new and powerful smart materials as actuators and sensors to shape control of smart structures. The expected outcome ....Active shape control of large thin-walled structures using ferroelectric single crystals. Ferroelectric single crystals were invented 5 years ago, and they possess many superior properties compared to conventional piezoelectric materials, particularly the induced strain up to 1.5%, an order higher than conventional materials. This project aims to poineer the application of these new and powerful smart materials as actuators and sensors to shape control of smart structures. The expected outcomes are (a) a new constitutive theory for the non-linear behaviour of ferroelectric single crystals; (b) a novel definition and formulation for the shape control problem; and (c) an innovative theoretical framework for design optimization of shape control of smart structures using ferroelectric single crystals.Read moreRead less
Morphing flexible structures with lead lanthanum zirconium titanate (PLZT) based optical actuators. Lead lanthanum zirconate titanate (PLZT) materials yield mechanical strains when exposed to near ultraviolet light as a result of combined photovoltaic and converse piezoelectric effects. They offer actuation strain on par with piezoelectric materials and other advantages, such as wireless light-to-mechanical energy transfer, immunity from electrical and magnetic disturbances and fast response wi ....Morphing flexible structures with lead lanthanum zirconium titanate (PLZT) based optical actuators. Lead lanthanum zirconate titanate (PLZT) materials yield mechanical strains when exposed to near ultraviolet light as a result of combined photovoltaic and converse piezoelectric effects. They offer actuation strain on par with piezoelectric materials and other advantages, such as wireless light-to-mechanical energy transfer, immunity from electrical and magnetic disturbances and fast response with the transparent electrode design. This project aims to pioneer the application of PLZT optical actuators in morphing flexible structures leading to development of wireless smart structures technology and opt-electromechanical systems such as medical instruments.Read moreRead less
Assessment and Prediction of Particle Breakage under Cyclic Loading. Every year, transport industries spend millions of dollars to maintain existing tracks suffering excessive settlement due to heavy traffic. In railways, differential settlement and track fouling are mostly due to ballast breakage. Frequent maintenance requires large amounts of quarried ballast causing environmental degradation. Simulation of particle breakage subject to cyclic loading is pioneering fundamental research that wi ....Assessment and Prediction of Particle Breakage under Cyclic Loading. Every year, transport industries spend millions of dollars to maintain existing tracks suffering excessive settlement due to heavy traffic. In railways, differential settlement and track fouling are mostly due to ballast breakage. Frequent maintenance requires large amounts of quarried ballast causing environmental degradation. Simulation of particle breakage subject to cyclic loading is pioneering fundamental research that will have significant impact on the design and maintenance of future rail and road networks. A full understanding of the breakage mechanisms of aggregates will lead to innovative techniques in design and construction, including faster trains carrying heavier loads with reduced maintenance costs.Read moreRead less