A Cluster RCT Of The Impact Of A Community-based Hygiene And Sanitation Programme On Infection With Intestinal Parasites Following Mass Albendazole Chemotherapy In Timor-Leste
Funder
National Health and Medical Research Council
Funding Amount
$1,178,136.00
Summary
Intestinal parasites cause anaemia, stunting, wasting and poor mental development in childhood, and are related to poverty and poor hygiene. Treatment with antiparasitic drugs cures infections in human hosts, but does not prevent rapid re-infection when people contact a parasite-contaminated environment. We will quantify the impact of a hygiene and sanitation programme that reduces environmental contamination in communities that receive mass treatment with the antiparasitic drug albendazole.
Regulation Of Macrophage Function And Gene Expression By The Th2-Promoting Stimulus, ES-62
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to c ....White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to certain diseases including asthma and diseases associated with intracellular infections. We are identifying genes expressed in macrophages during these immune responses that are likely to be involved in susceptibility to such diseases.Read moreRead less
Haemoglobin Degrading Proteases As Targets Of Anti-hookworm Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
Blood-feeding worms ingest red blood cells and disrupt them in the intestine, releasing haemogobin (Hb). We have recently shown that canine hookworms employ a battery of distinct proteolytic enzymes, termed haemoglobinases, which digest Hb. The families of proteases used and the order in which they act are strikingly similar to the defined catalytic pathway used by the malaria parasite to digest Hb in its food vacuole. Recent work from our laboratory has shown that these proteases are effective ....Blood-feeding worms ingest red blood cells and disrupt them in the intestine, releasing haemogobin (Hb). We have recently shown that canine hookworms employ a battery of distinct proteolytic enzymes, termed haemoglobinases, which digest Hb. The families of proteases used and the order in which they act are strikingly similar to the defined catalytic pathway used by the malaria parasite to digest Hb in its food vacuole. Recent work from our laboratory has shown that these proteases are effective as vaccines against canine hookworm disease by interfering with the worm's ability to feed on blood and obtain suitable nutrition. This in turn affects the ability of female worms to lay eggs, thereby potentially disrupting transmission of the parasites. We now propose to identify the genes encoding haemoglobinases from the human hookworm, Necator americanus, determine the ordered pathway of Hb degradation and explore in vitro correlates of the effectiveness of a haemoglobinase vaccine in animal models of hookworm infection and pathogenesis.Read moreRead less
Understanding Interactions Between Eosinophils And Tissue-Invasive Parasitic Helminths
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Eosinophils are blood cells which contribute to our defences against parasitic worms. Given the right opportunity, eosinophils can cause damage to some parasites within just a few hours of contact. This is quite a feat because parasitic worms are multicellular organisms which are much larger than eosinophils and which have evolved to live in the presence of active immune responses. To do it's job properly an eosinophil probably makes use of small soluble molecules in the blood and others fixed t ....Eosinophils are blood cells which contribute to our defences against parasitic worms. Given the right opportunity, eosinophils can cause damage to some parasites within just a few hours of contact. This is quite a feat because parasitic worms are multicellular organisms which are much larger than eosinophils and which have evolved to live in the presence of active immune responses. To do it's job properly an eosinophil probably makes use of small soluble molecules in the blood and others fixed to it's own cell surface, to recognize the parasite and to promote adhesion to the target. You might like to consider these molecules as hands grabbing onto handles on the surface of the parasite. The more hands there are, the better the grip and some hands grip more strongly than others. We are investigating what these molecules are and how they work. By understanding how eosinophils operate, we may be able to devise ways in which we can make them more effective. We are also trying to understand why some species of parasite are resistant to attack by eosinophils. We think that resistant parasites secrete substances which either block the binding of eosinophils to the parasite surface, or prevent the functioning of eosinophils that do bind. It is possible that these inhibitory substances may even kill the eosinophils before they can do their job. Resistant parasites might induce eosinophils to commit suicide, a useful property for us when we no longer need these cells, but a definite drawback if they still have a job to do. Parasitic worms have evolved to avoid at least some of our defences and sometimes they do this by mimicing natural processes important for regulating immune responses. In some diseases like asthma and allergy eosinophils slip from normal controls which regulate them and then they can cause tissue damage. Inhibitors of eosinophils which are produced by parasites might form the basis of new drugs to control these cells in diseases like asthma.Read moreRead less
Dissection Of The Mechanisms Of Action Of Evolutionarily Conserved Apoptotic Pathway Components
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Animals eliminate unwanted cells through a highly controlled process termed apoptosis. Defects in apoptosis can contribute to cancer or autoimmune disease. Conversely, diseases such as stroke and Alzheimer's disease have been linked to excessive cell death. To develop drugs that promote apoptosis when it fails to occur, or prevent inappropriate cell death, it is necessary to elucidate the molecular mechanisms controlling apoptosis. The first recognised component of the mammalian cell death machi ....Animals eliminate unwanted cells through a highly controlled process termed apoptosis. Defects in apoptosis can contribute to cancer or autoimmune disease. Conversely, diseases such as stroke and Alzheimer's disease have been linked to excessive cell death. To develop drugs that promote apoptosis when it fails to occur, or prevent inappropriate cell death, it is necessary to elucidate the molecular mechanisms controlling apoptosis. The first recognised component of the mammalian cell death machinery was Bcl-2; a protein associated with development of cancer. Despite much research since then, the way in which Bcl-2 and related proteins function is still unknown. This project capitalises on previous genetic and biochemical studies in a model genetic organism (the roundworm) to address this important issue. Animal cell death pathway components can be introduced into yeast such that activation of the introduced pathways leads to yeast death and its inhibition promotes yeast survival. We have used this approach to reconstitute the worm cell death pathway and a major mammalian apoptosis pathway in yeast. Yeast strains bearing these reconstituted pathways will be used to test functional equivalence of candidate mammalian proteins and their putative roundworm counterparts. The system will also be exploited to identify and characterise novel proteins that regulate cell death in mammals and worms. Understanding the way in which key molecules regulate apoptosis will assist in the development of diagnostic and therapeutic reagents for many diseases in which cell death regulation is perturbed. This project capitalises on the evolutionary conservation of apoptosis to characterise the mechanisms of action of important mammalian apoptotic regulators and to seek novel mammalian apoptotic pathway components. Proteins identified in this way are likely to be important apoptotic regulators, as our approach ensures that their functions are evolutionarily conserved.Read moreRead less
Antibiotic Treatment Of Male Partners To Reduce Recurrence Of Bacterial Vaginosis In Women: A Randomised Double-blind Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$636,674.00
Summary
Bacterial vaginosis (BV) is the most common vaginal infection in women. Healthy bacteria are lost and replaced by bacteria that cause unpleasant discharge and odour. BV puts women at increased risk of sexually transmitted infections, HIV, miscarriage and preterm delivery. Over 50% of women given antibiotics get BV back again. Studies suggest these bacteria are being sexually transmitted. We are conducting a trial of antibiotic treatment of women and their male partners to improve BV cure.
The Impact Of Household Infrastructure Improvements On Child Health In Remote Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$413,350.00
Summary
The impact of the living environment on health has been well documented in the last 150 years and it is widely acknowledged that improvements in the living, working and social conditions of industrial countries have resulted in dramatic improvements in health. In Australia the close correlation between an unhealthy environment and the poor health of the Indigenous population has been clearly recognised. In 1993-94 the Federal Government established infrastructure projects as a component in the i ....The impact of the living environment on health has been well documented in the last 150 years and it is widely acknowledged that improvements in the living, working and social conditions of industrial countries have resulted in dramatic improvements in health. In Australia the close correlation between an unhealthy environment and the poor health of the Indigenous population has been clearly recognised. In 1993-94 the Federal Government established infrastructure projects as a component in the implementation of the National Aboriginal Health Strategy. The selection of communities for funding has been based on need, and the Northern Territory has attracted funding support disproportionate to its total population, but consistent with the level of need. While there is wide acceptance of the relationship between the household environment and health status, and evidence to support this general relationship, there is a need at an international and local level for research that informs specific social policy decisions. The aim of the proposed study is to determine the impact of improvements in household infrastructure on the health of children living in remote Aboriginal communities with a view to informing the development of infrastructure projects. The outcomes of this project will be a significant advance in the understanding of the relationship between the household environment and health status, and of the improvements in health that can be achieved through improvement in household infrastructure. The relationship between specific components of household infrastructure and the ability to conduct each of a number of healthy living practices will be defined, to our knowledge, for the first time. There is a unique opportunity in the Northern Territory to conduct world class research in this area. The new information will be of value in the planning of infrastructure projects in remote Indigenous communities across Australia and in similar settings internationallyRead moreRead less
Viral Factors Involved In Flavivirus Replication And Virus-host Interactions
Funder
National Health and Medical Research Council
Funding Amount
$743,696.00
Summary
With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the researc ....With our increased understanding of virus-host interactions it has become apparent that small, non-structural proteins and small RNAs of most viruses are vital for numerous, often multiple, functions in the viral life cycle. In the proposed project, we seek to gain a detailed understanding of the functions of small nonstructural protein NS2A and small abundant viral RNAs of medicaly important encephalitic flaviviruses, which have remained so far elusive and are at the cutting-edge in the research field. We anticipate that with a better understanding of the roles of these factors in flaviviral replication and pathogenesis, novel targets for antiviral therapies and-or molecular determinants for inclusion in candidate vaccines will be identified.Read moreRead less