IDENTIFICATION OF BRAIN NEURONS INVOLVED IN THE CARDIOVASCULAR RESPONSE TO FEAR AND FLIGHT
Funder
National Health and Medical Research Council
Funding Amount
$400,247.00
Summary
The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vess ....The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vessels which restrict the flow of blood to the tissues. These nerves, in turn, are under the control of brain cells or neurons which are located in the brainstem. Blood pressure-controlling neurons, acting upon information they receive from pressure sensors in the major blood vessels in the chest cavity, can alter their activity so that blood pressure is maintained within normal limits. Our laboratory has been examining the properties of these blood pressure-controlling neurons by recording their minute electrical discharges and by studying other brain regions which are able to influence them. In this study, we will use newly-developed procedures which will allow us to identify the precise locations of these neurons in the brain, to study which neurotransmitters (chemicals released by neurons which are used to communicate with other neurons) they use, as well as to identify other regions of the brain they connect with and influence. The major significance of this work will be that new brain circuits which transmit information about the status of the cardiovascular system to other areas of the brain will be identified. Our understanding of, and the development of new treatments for, cardiovascular diseases such as high blood pressure and heart failure are critically dependent on advancing our understanding of the nervous system.Read moreRead less
UTILITY OF NOVEL BIOMARKERS IN THE PREDICTION OF MAJOR COMPLICATIONS OF TYPE II DIABETES MELLITUS
Funder
National Health and Medical Research Council
Funding Amount
$510,639.00
Summary
Diabetes is increasingly common. It can cause a variety of complications, the most serious being heart and kidney disease. The reasons why some patients develop such complications are not fully understood so it is difficult to predict who will be affected. The current project will use samples from a large international study of patients with diabetes to assess whether levels of specific markers in the blood help to predict major complications and clarify why they occur.
Inflammation of the kidneys is an important, yet poorly understood cause of kidney disease in Australia. This project will define the role of some of the immune cells, called Th17, that usually act to protect us from infection, but can turn rouge and may cause kidney damage.
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. The aim of the project is to determine how these white blood cells accumulate in the glomerulus, specifically asking the question, what molecules present on the white blood cells and the glomerular blood vessels are required for this accumulation?
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.
TLR9 AGGRAVATES GLOMERULONEPHRITIS AND KIDNEY INJURY IN RENAL VASCULITIS
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Renal failure is a significant cause of morbidity and mortality in Australia. Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis associated glomerulonephritis (GN) is a significant cause of renal failure. The molecular mechanisms underlying ANCA vasculitis are poorly understood, while treatments are associated with considerable morbidity and mortality. This grant aims to explore key molecular events involved in the disease pathogenesis to facilitate the use of safer more targeted therapies.
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
I am a clinician scientist and nephrologist. My research involves preclinical and clinical translational approaches to identify new targets and develop novel treatments to prevent, reverse and retard the development and progression of diabetic complications.
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
The Therapeutic Role Of Complement Inhibition In ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$600,964.00
Summary
ANCA associated vasculitis is an inflammatory disease involving the kidney filters which is a major cause of chronic kidney failure. Current drugs to treat it are toxic. Less toxic treatments are required. In this study we will explore the potential for new treatments targeting complement (a normal blood protein involved in inflammation) to attenuate this disease in mice. We hope to define the role of complement in this disease and the benefits of inhibiting it before we use it in humans.