Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
New multi-scale seed dispersal models for improved regional weed management. This project will exploit recent advances in ecological and atmospheric modelling with the aim to build improved models of seed dispersal across landscapes to anticipate weed spread. Damaging invasive plants are rapidly transforming landscapes and altering ecosystem function worldwide. The speed and direction of weed spread determines the success or failure of costly containment and control actions, however we lack the ....New multi-scale seed dispersal models for improved regional weed management. This project will exploit recent advances in ecological and atmospheric modelling with the aim to build improved models of seed dispersal across landscapes to anticipate weed spread. Damaging invasive plants are rapidly transforming landscapes and altering ecosystem function worldwide. The speed and direction of weed spread determines the success or failure of costly containment and control actions, however we lack the ability to adequately predict spread. New models that combine micrometeorological measurements, within-canopy turbulence and topographic variation in wind flows will be designed to better predict where dispersal will occur. In this project, these improved predictions are planned to be combined with decision models to direct the management of invasive species across entire landscapes.Read moreRead less
Understanding snow gum dieback for effective and integrated management. The project leverages recent research and infrastructure investments and our determined and collaborative team as it aims to: 1) assess the future geography of snow gum dieback in the high country and identify priority locations for pro-active management, 2) quantify the impact of snow gums on high country water and carbon budgets and thus the socio- economic and biodiversity values, and 3) determine options for mitigation. ....Understanding snow gum dieback for effective and integrated management. The project leverages recent research and infrastructure investments and our determined and collaborative team as it aims to: 1) assess the future geography of snow gum dieback in the high country and identify priority locations for pro-active management, 2) quantify the impact of snow gums on high country water and carbon budgets and thus the socio- economic and biodiversity values, and 3) determine options for mitigation. Dieback of our iconic snow gum forests is diminishing the ecological, hydrological and cultural values of the Australian Alps and will impact state and national water-supply and power-generation systems. Our research will inform Alps-wide management efforts designed for long-term success.Read moreRead less
Extracting subtle hints for new phenomena at the Large Hadron Collider. This project aims to investigate the detailed nature of the Higgs theory which underpins the mass of elementary particles. The project aims to increase the understanding of particle interactions in the context of precise measurements of the properties of the Higgs boson that will come out of the experimental program at the large hadron collider. Expected outcomes include the development and application of methods to address ....Extracting subtle hints for new phenomena at the Large Hadron Collider. This project aims to investigate the detailed nature of the Higgs theory which underpins the mass of elementary particles. The project aims to increase the understanding of particle interactions in the context of precise measurements of the properties of the Higgs boson that will come out of the experimental program at the large hadron collider. Expected outcomes include the development and application of methods to address existing gaps in the framework that confronts theory and experiment and to efficiently explore its high dimensionality. The benefits of conducting this research in Australia include the development of intellectual culture and the training of early-career researchers as flexible problem solvers in academia or beyond. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100867
Funder
Australian Research Council
Funding Amount
$367,518.00
Summary
Bridging the accuracy gap: High-precision parton showers for colliders. This project aims at improving the accuracy of parton showers, which are an essential ingredient used in the simulation of high-energy particle collisions. Parton showers generate the large set of particles produced in a collision, in an approximation of the radiation pattern of Quantum Chromodynamics. The low precision of this approximation translates into large uncertainties in critical measurements performed at particle c ....Bridging the accuracy gap: High-precision parton showers for colliders. This project aims at improving the accuracy of parton showers, which are an essential ingredient used in the simulation of high-energy particle collisions. Parton showers generate the large set of particles produced in a collision, in an approximation of the radiation pattern of Quantum Chromodynamics. The low precision of this approximation translates into large uncertainties in critical measurements performed at particle colliders. This project will study novel ways of enhancing the precision of parton showers, and determine accurate estimates of associated uncertainties across all processes under investigation at the Large Hadron Collider. It will be of exceptional importance for the latter's high-precision, high-luminosity program.Read moreRead less
Beautiful strings. This project aims to carry out several key experimental measurements, in tandem with substantial theoretical work, to improve the understanding and physical modelling of processes involving b quarks, also called beauty quarks, which are of intense current interest for experiments across the globe. Key theoretical innovations include novel treatments of electromagnetic corrections, novel theoretical formulations of the dominant physical paradigm of string fragmentation, and opt ....Beautiful strings. This project aims to carry out several key experimental measurements, in tandem with substantial theoretical work, to improve the understanding and physical modelling of processes involving b quarks, also called beauty quarks, which are of intense current interest for experiments across the globe. Key theoretical innovations include novel treatments of electromagnetic corrections, novel theoretical formulations of the dominant physical paradigm of string fragmentation, and optimisations of key associated algorithms to enable new applications of broad relevance. Experimental measurements will be carried out to validate the new theoretical developments and use them to minimise theoretical uncertainties.Read moreRead less
Building resilient alpine environments with less snow. In this project, we aim to build resilience into alpine National Parks and Alpine Resorts to counter the effects of ongoing declines in snow. Alpine environments depend on snow to regulate water flows, insulate vegetation, control soil erosion and promote proper ecosystem functioning. How these processes will operate in a snow-free future is unknown. We will determine how and where snow characteristics drive soil water availability for plant ....Building resilient alpine environments with less snow. In this project, we aim to build resilience into alpine National Parks and Alpine Resorts to counter the effects of ongoing declines in snow. Alpine environments depend on snow to regulate water flows, insulate vegetation, control soil erosion and promote proper ecosystem functioning. How these processes will operate in a snow-free future is unknown. We will determine how and where snow characteristics drive soil water availability for plants and which plant species have the best adaptation and regeneration potential under extreme conditions such as heat, frost and drought. Benefits of the project include innovative land management and rehabilitation solutions, to safeguard Australia's alpine areas under changing environmental conditions.Read moreRead less
Mitigating extreme water supply contamination in bushfire burned catchments. This project involves Melbourne Water, the Department of Environment and Primary Industries, and East Gippsland Water in developing tools to evaluate mitigation options that will protect our water supplies and increase the resilience of Australian communities to bushfire. Major bushfires in south-east Australia in 2003, 2007, 2009 and 2013 were followed by storms that triggered extreme soil erosion events in catchments, ....Mitigating extreme water supply contamination in bushfire burned catchments. This project involves Melbourne Water, the Department of Environment and Primary Industries, and East Gippsland Water in developing tools to evaluate mitigation options that will protect our water supplies and increase the resilience of Australian communities to bushfire. Major bushfires in south-east Australia in 2003, 2007, 2009 and 2013 were followed by storms that triggered extreme soil erosion events in catchments, contaminating water supplies and damaging critical infrastructure. The capacity to mitigate the risk of interruption to the water supplies of our cities and towns in a more fire-prone future is currently limited by our knowledge of where, why, and how often these post-fire contamination events will occur. This project aims to address these knowledge gaps.Read moreRead less