Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failu ....Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failure. It will also provide us with a significant understanding of the role in reflex sympathetic nerve regulation of an important brain region known as the hypothalamic paraventricular nucleus (PVN). Our findings will help us understand the nature of the neurotransmitters contributing to the reflex nerve regulation and the specific neurons within the PVN involved. This knowledge could help us to identify novel potential therapeutic targets within the brain to alleviate the problems observed in heart failure.Read moreRead less
Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will ....Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will attempt, for the first time, to define the location in the cerebral cortex of the drive to ingest water (perception of thirst).Read moreRead less
Ion Transport In The Human Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. However, despite the significance of the malaria parasite for world health, the basic physiology of th ....Malaria is responsible for hundreds of millions of cases and an estimated 1.5-2.7 million deaths each year. The disease is caused by a microscopic parasite which is becoming increasingly resistant to antimalarial drugs. There is a very real possibility that there will soon be parts of the world in which malaria is an untreatable disease, and there is an urgent need to identify new drug targets. However, despite the significance of the malaria parasite for world health, the basic physiology of this organism is poorly understood. This project focuses on the mechanisms involved in ion balance in the parasite. Ion balance is a basic 'housekeeping' function in all cells, and disruption of the mechanisms involved will inevitably impair cell function. The work proposed here will lead to an understanding of ion balance in the intracellular parasite and provide insight into whether the mechanisms involved may be suitable antimalarial drug targets.Read moreRead less
Neural Mechanisms Mediating Inhibitory Influences Of Hyperthermia, Fever And Age On Water Intake
Funder
National Health and Medical Research Council
Funding Amount
$324,125.00
Summary
An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand ....An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand mechanisms by which the thirst mechanism in the brain is supressed. We have observed that a high body temperature may have an inhibitory influence on thirst in rats, and it is also known that thirst mechanisms are depressed in elderly people. If we can identify the regions of the brain that are involved and the mechanisms underpinning this reduced thirst, then it will be possible to identify and alert people at risk and to design strategies to prevent dangerous levels of dehydration occurring due to reduced thirst, particularly in the elderly. This may also apply to to people who may be working or undertaking vigorous exercise in hot weather or taking certain medications.Read moreRead less
Type 2 diabetes causes significant health problems. The fundamental reasons underlying this disease are not fully known and will require molecular analysis of proteins critical to blood glucose control. This work aims to define a novel pathway that responds to circulating nutrients. The research will enhance our understanding of the links between diet and metabolic disease, with potential to reveal much needed therapeutic targets and/or dietary interventions for the treatment of Type 2 diabetes.
The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
The Generation, Fate And Functional Potential Of Recent Thymic Emigrants
Funder
National Health and Medical Research Council
Funding Amount
$318,856.00
Summary
A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called auto ....A particular kind of white blood cell, called a T lymphocyte, is responsible for controlling our immune responses to foreign invaders. These cells develop in the thymus, where they learn to distinguish between foreign invaders and self tissue, before emigrating to other organs. The regulation of this process is important to maintain a pool of T lymphocytes in the body. It is important that T lymphocytes do not respond against self tissue, as this can lead to a Oself destructO disease called autoimmunity. Since these developing T lymphocytes will not see all kinds of self tissue while in the thymus, we propose that their education to prevent self-tissue reactivity may continue for some time after they leave the thymus.Read moreRead less