Characterisation Of The Anti-inflammatory Properties Of The N-3 Fatty Acid Product, 4-hydroxy-hexenal.
Funder
National Health and Medical Research Council
Funding Amount
$524,559.00
Summary
A concerted effort is being made by experts in the field of omega 3 fats (fish oils) to make specific recommendation on their use to improve human health . We have reasoned that the characterisation of a major oxidation product of these oils could be a key to understanding how these fats benefit us. The project is likely to influence the formulation of fish oils to enhance their health promoting properties.
Defining The Role Of Lymphotoxin Alpha In Experimental Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$158,250.00
Summary
Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often deat ....Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often death. The factors that cause the sequestration of iRBC in the brain are poorly understood. In this project, we will use an experimental model to define the changes that occur in the cerebral vessels during malaria. The identity of the cells and molecules that mediate the binding of iRBC to the blood vessels of the brain will be identified. It is anticipated that results from this work will increase our understanding of the development of pathology in the brain, as well as identify potential targets for modulation to prevent disease.Read moreRead less
Cytokines Regulating Airway Inflammation, Remodelling And Hyper-reactivity In Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$329,500.00
Summary
This project examines a new approach to treatment of asthma, based on immunisation against the body's own chemical signals. The investigators will also be continuing studies on how twitchy airways develop in asthma, the mechanisms by which scarring of the airway walls progresses, and the signals that trigger inflammation of the airways. These studies will use a much-improved mouse model of the disease. In this experimental model, which was developed by the investigators, sensitised mice are chro ....This project examines a new approach to treatment of asthma, based on immunisation against the body's own chemical signals. The investigators will also be continuing studies on how twitchy airways develop in asthma, the mechanisms by which scarring of the airway walls progresses, and the signals that trigger inflammation of the airways. These studies will use a much-improved mouse model of the disease. In this experimental model, which was developed by the investigators, sensitised mice are chronically exposed to low concentrations of aerosolised egg white protein. The proposed studies will involve comparisons with animals that are immunised against certain inflammation-related molecules, as well as with mice that are genetically deficient in their ability to produce such molecules. The results of these studies may help in the development of methods for long-term suppression of the changes that develop in the airways of asthmatics.Read moreRead less
Defining The Role Of Tumour Necrosis Factor Apoptosis Inducing Ligand (TRAIL) In Experimental Visceral Leishmaniasis.
Funder
National Health and Medical Research Council
Funding Amount
$153,250.00
Summary
The activation of pathogen-specific T cells by dendritic cells (DC) is a critical step in the control of most infections, as well as the success of many vaccine strategies. The specific cells and molecules involved in this process are still poorly defined. In this project, we will investigate the effects of a cell surface molecule called tumour necrosis factor related apoptosis inducing ligand (TRAIL) on the ability of DC to activate T cells during a parasitic infection caused by Leishmania dono ....The activation of pathogen-specific T cells by dendritic cells (DC) is a critical step in the control of most infections, as well as the success of many vaccine strategies. The specific cells and molecules involved in this process are still poorly defined. In this project, we will investigate the effects of a cell surface molecule called tumour necrosis factor related apoptosis inducing ligand (TRAIL) on the ability of DC to activate T cells during a parasitic infection caused by Leishmania donovani. By identifying the cells that express TRAIL and the effect that this molecule has on the development of immunity to pathogens, we will better understand the factors required to generate effective immune responses against infectious agents, and hence, develop better vaccines.Read moreRead less
INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem w ....Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.Read moreRead less
The Effect Of Hepatic Pseudocapillarisation Of Old Age On The Disposition Of Chylomicron Remnants And Chylomicrons
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the li ....Old age is the major risk factor for atherosclerosis, and vascular disease secondary to atherosclerosis (eg heart attacks and strokes) is the major cause of death and disability in the Western World. As yet there has not been any clear explanation for why old age itself is a risk factor for atherosclerosis. In this study, we are investigating how changes in the liver in old age predispose to hyperlipidaemia and hence vascular disease. We recently discovered changes in the blood vessels of the liver that occur with old age that we have called pseudocapillarisation. These changes have profound effects on the transport of many substrates including toxins, drugs, oxygen, hormones and lipids from the blood into the liver and thus may explain in part the fact that old age is the major risk factor for many diseases and adverse drug reactions. In this study we are interested in the transfer of fats called chylomicron remnants from blood into the liver. Chylomicron remnants are lipoproteins rich in triglycerides that are produced after meals and broken down by the liver. In order to be metabolised, chylomicron remnants must pass through pores in the liver blood vessels called fenestrations. In old age, we have found that these fenestrations are reduced substantially, which will impair the uptake of chylomicron remnants by the liver, leading to marked increases in fat in the blood stream after meals. In this study, we will examine the effects of old age on the ability of the liver to metabolise chylomicron remnants, in particular focussing on the effects of the age-related loss of fenestrations on chylomicron remnant uptake. As well as providing an understanding of the crucial link between ageing and atherosclerosis, the studies will provide a potential new therapeutic target for the prevention of atherosclerosis in older people.Read moreRead less
All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these ....All cells have a characteristic shape (morphology), which is intrinsic to cellular function. A blood cell is designed to move in a liquid medium whereas a muscle cell is optimised for physical movement of attached bones. We are studying the mechanisms which control cell shape. We focus on the components of the cell skeleton (cytoskeleton) which are implicated in the regulation of shape. In particular, we study the actin based microfilament system. We have previously shown that two types of these components of the cytoskeleton are able to control the structure of cells. In addition, we have found that variants of these two components (called isoforms) are used to build structures in different parts of cells. This has led us to think about the anatomy of cells and tissues in a new way. In some ways its like building a city. You create different kinds of buildings to suit their purpose. Each building uses a combination of building blocks which suit the structural demands of rooms and the overall building. In this study, we are proposing to dissect out genes, or parts of genes, which supply specific types of building blocks. To do this, we plan to change these genes in mice and then examine the impact on cell and tissue anatomy. This promises to contribute to the conversion of anatomical science and pathology from descriptive to experimental-mechanistic disciplines.Read moreRead less