Targeting The AGE-RAGE Axis In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$542,859.00
Summary
Based on extensive preliminary data we porpose that the AGE intercation with RAGE plays an important role in diabetes associated atherosclerosis. We will perform studies using a soluble form of the receptor RAGE which will trap AGEs in the blood and tissues and thus prevent diabetes related blood vessel damage. Furthermore, we will investigate if RAGE receptor on inflammatory cells such as macrophages plays a pivotal role in blood vessel injury in diabetes.
Circulating Low -molecular Weight AGEs In The Development And Progression Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$297,523.00
Summary
High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific rec ....High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetesRead moreRead less
Modulating Pathogenic Signalling Towards The Prevention Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Diabetes is associated with an increased risk of heart attacks and kidney failure. There remains an urgent need for new targets and therapies for preventing, arresting, treating and reversing these diabetic complications. My research directly focuses on identifying and validating these targets treatments, building on strong preliminary data and understanding of the molecular mechanisms set off by high sugar levels.
The Role Of Dicarbonyl-derived AGEs And RAGE In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$470,617.00
Summary
Based on our pilot data we postulate that glucose derived molecules such as methylglyoxal (MGO) have effects on inflammation and oxidative stress leading to accelerated atherosclerosis in diabetes. Our studies aim to identify novel treatments which block these effects thus leading to superior protection and prevention of atherosclerosis in diabetes.
Prospective Longitudinal Study - Symptom Clusters & Their Effects - Physical & Psychogical Functioning Patients Metastat
Funder
National Health and Medical Research Council
Funding Amount
$149,599.00
Summary
People with advanced cancer often experience several concurrent debilitating symptoms, yet most symptom research focuses on the study of individual symptoms. This study aims to gain a better understanding of the patterns and effects of specific groups of symptoms across the trajectory of a patient's illness following diagnosis of advanced cancer. Such knowledge is critical to the development of more focused symptom assessment processes and more appropriately targeted interventions.
The Role Of Renal Dendritic Cells In Infection And Immunity Under Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$475,143.00
Summary
Kidney transplantation is the best treatment for kidney failure but it is frequently complicated by bacterial and viral infections that can cause rejection and may cause loss of the kidney. This grant will study the role that dendritic cells in the kidney play in causing rejection and preventing infection. With the knowledge gained from these studies, we will be able to discover new ways to prevent rejection and treat infections of the kidney post transplant.
New Wrought Magnesium Alloys: Manipulating the Annealed Microstructure. One of the main impediments to increased use of wrought magnesium is its characteristic but mediocre mechanical properties. The proposed work paves the way for new improved wrought magnesium alloys by determining how the constituent nano-structures, micro-structures and deformation conditions can be manipulated to control the evolution of properties during annealing. The project will deliver mathematical models describing th ....New Wrought Magnesium Alloys: Manipulating the Annealed Microstructure. One of the main impediments to increased use of wrought magnesium is its characteristic but mediocre mechanical properties. The proposed work paves the way for new improved wrought magnesium alloys by determining how the constituent nano-structures, micro-structures and deformation conditions can be manipulated to control the evolution of properties during annealing. The project will deliver mathematical models describing the annealed microstructure and mechanical properties. The work will also explore the potential of a recent discovery made by the CI of a simple technique to randomise the alignment of the annealed atomic lattice structure, which promises to markedly improve formability.Read moreRead less
Modelling twinning transitions in light metals: a new foundation for alloy and process development. Australia's quest to become a world leader in light metals technology is being held back by a lack of quantitative understanding of the metallurgical behaviour of magnesium, which is the lightest engineering metal, and titanium, which is the strongest light metal. In particular, there is poor knowledge of the influence of material parameters on deformation twinning. This knowledge is vital for eff ....Modelling twinning transitions in light metals: a new foundation for alloy and process development. Australia's quest to become a world leader in light metals technology is being held back by a lack of quantitative understanding of the metallurgical behaviour of magnesium, which is the lightest engineering metal, and titanium, which is the strongest light metal. In particular, there is poor knowledge of the influence of material parameters on deformation twinning. This knowledge is vital for efficient production and optimised alloy and part design. This proposal aims to develop a quantitative understanding of transitions in twinning activation for improved performance in fatigue, crash behaviour, structural integrity, forming, forging, extruding, hot rolling and annealing.Read moreRead less
The development of lead-free silicon brass for the plumbing industry. The worldwide brass industry is currently undergoing a transition away from lead-containing brass water fittings to lead-free fittings. The transition is driven by concerns surrounding lead-leaching into drinking water. This project is focussed on the development of new lead-free brasses that can be used to manufacture plumbing fittings with superior combinations of processability, performance and cost.