From Maps To Efficient Multi-parasite Control In The Philippines
Funder
National Health and Medical Research Council
Funding Amount
$358,121.00
Summary
Schistosomiasis and soil-transmitted helminths are major parasitic infections in Asia, causing anaemia, poor growth and poor school performance and death in some chronic schistosomiasis cases. We will use maps to demonstrate the geographic distribution of these parasites in the Philippines. We will estimate the impact and costs and benefits of parasite control programmes. This research will help plan more efficient parasite control and reduce the impact of these infections in the Philippines.
Development And Application Of Theoretical Models Of Plasmodium Transmission To Guide Malaria Elimination Efforts
Funder
National Health and Medical Research Council
Funding Amount
$315,401.00
Summary
There is currently a worldwide endeavour to eliminate malaria but there are few tools available to evaluate the impact of intervention strategies in the Asia-Pacific region. This project aims to address this deficiency by developing simulation models of Plasmodium vivax and mixed species infections, and using these new tools to investigate the likely impact of a variety of intervention strategies including bed nets, improved access to treatment and mass drug administration.
Modelling The Effects Of Immunity On Influenza Transmission - Implications For Prevention And Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$275,767.00
Summary
There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our proj ....There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our project will use data from historic and contemporary outbreaks of influenza and build mathematical models to explain the rate of growth of an influenza outbreak in terms of: 1. The proportion of people exposed to influenza who do not become ill (although there can be evidence of infection if careful studies are made). This proportion is about 33%. 2. The proportion of people who are protected from influenza by immunity, whether induced by vaccination or by past exposure to natural influenza infection (this can vary from 0% in isolated populations which have not seen influenza for many years up to 80 or 90% in urbanised populations that are exposed to influenza almost every season). 3. Different rates of contact between different people and groups of people - some may be exposed so often that their immunity is boosted regularly without them becoming severely ill; others, living in more isolated circumstances, may be rarely exposed, but when they are, they are more likely to become severely ill. 4. The effects of influenza vaccine in inducing protective immunity - it is well known that there is good protection if the vaccine is well matched to the circulating virus. 5. The effects of live virus infection in inducing (short-lived) protection against a wider range of influenza viruses. Our model results will be used to guide vaccine design and pandemic planning.Read moreRead less
Role Of ApoCIII In The Regulation Of Lipoprotein Metabolism In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$240,320.00
Summary
Obesity is an increasing problem in Australia. Associated with the state of obesity are elevated levels of blood fats and thus an increased risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In obesity, the secretion of blood fats, or lipoproteins, is elevated compared with non-obese individuals. In addition, the mechanisms responsible for the clearance of these fats from the blood are impaired resulting in elevated levels of fat circulating ....Obesity is an increasing problem in Australia. Associated with the state of obesity are elevated levels of blood fats and thus an increased risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In obesity, the secretion of blood fats, or lipoproteins, is elevated compared with non-obese individuals. In addition, the mechanisms responsible for the clearance of these fats from the blood are impaired resulting in elevated levels of fat circulating in the body. A particular protein, called apolipoprotein CIII, plays an important role in the regulation of lipoprotein metabolism. Obese subjects have elevated levels of this apoprotein and we have hypothesised that this is responsible for the impaired lipoprotein clearance observed in these subjects. In general, obese subjects are insulin resistant, although they may not be frank diabetics. Blood insulin levels regulate apolipoprotein CIII concentrations, however, in a state of insulin resistance, as seen in obese subjects, apolipoprotein CIII levels are elevated resulting in high blood fat levels. The focus of this research project is to determine if the level and production of apolipoprotein CIII is elevated in obese subjects compared with non-obese individuals by performing metabolic studies. In addition, we will investigate the effect of statins and fish oil, regulators of cholesterol and triglyceride synthesis respectively, on apolipoprotein CIII levels to assess the association between this and the clearance time of blood fats. If our hypothesis is correct, these studies will demonstrate a new mechanism of action of the statins and fish oil that will aid in the treatment of elevated blood fats and thus reduce the risk for heart disease in this important target population.Read moreRead less
Using Mathematical Models To Assess The Impact Of Interventions To Reduce Sexually Transmitted Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$562,276.00
Summary
Sexually transmitted infections (STIs) are an increasing public health problem in Australia. Australia's recent National Transmissible Infections Strategy identified chlamydia control, STI prevention in gay men and STIs in Aboriginal and Torres Strait Islander communities as priority areas. We propose to develop mathematical models of STI transmission and use these to help understand and identify the most cost-effective interventions to reduce the impact of STIs on Australian populations.
Mathematical Modelling Of Bacterial Carriage In Children
Funder
National Health and Medical Research Council
Funding Amount
$421,746.00
Summary
Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, child ....Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, children attending group child care are at high risk of ear infections. As many bacteria are resistant, antibiotics are now much less effective than when they were first introduced. Furthermore, there is a continuing load of infection for children in Aboriginal communities, in PNG and other developing countries, causing hearing loss, chronic respiratory problems, and heart disease and renal disease in later life. Using data previously collected from other studies in Indigenous communities and children in child care, mathematical models allow us to ask what if?, and answer important public health questions: 1. What environmental and public health measures can reduce the cycle of cross-infection in child-care and high-risk populations? 2. What coverage rates with pneumococcal vaccine will eliminate the vaccine-specific bacteria from child care centres, from the wider community, and from high risk populations? 3. Will infections with bacteria not covered by vaccine then increase? 4. Will the resistant bacteria tend to disappear if antibiotic use is restricted? 5. Under what circumstances will antibiotics help to control infection? The modelling will promote understanding of the social and health costs of bacterial infection in Aboriginal communities and child care and use educational scenarios to promote uptake of the most cost-effective and socially acceptable interventions.Read moreRead less
MEASURING AND MODELLING VISUAL CORTICAL PLASTICITY
Funder
National Health and Medical Research Council
Funding Amount
$612,693.00
Summary
We are the product of both our genes and our environment. Scientists have already shown that the physical structure of our brain can be changed by our experiences. But how much can it be changed? Our experiments will address this question for a particular case: how far our visual experiences can affect the structure of the part of our brain that processes visual images. This will help us understand the delicate balance between our genes and our environment in shaping who we are.
Biological And Mathematical Studies Of Development Of The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$390,250.00
Summary
During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which con ....During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which control gut function. In a common birth defect, Hirschsprung's disease, this migration stops short of the rectum so that the last part of the gut never develops nerve cells. This region lacking nerve cells is unable to propel the gut contents and, if untreated, this condition of intractable constipation is fatal after birth. Eight genes, when mutated, give essentially the same condition either in humans or animals, but the link between the genes and the condition is still not clear. We have proposed that the genes code for molecules that effect the way the neural crest cells interact with other neural crest cells and with the cells of the gut in which migration takes place. The link between the genes and the development of a normal gut nerve system (or its failure, as in Hirschsprung's disease) operates at the level of the dynamics of the neural crest cell population, interacting with the dynamics of gut growth. This project will use very detailed biological data acquisition to feed into newly formulated original mathematical models to tease out the important links between the neural crest cell population and the growing gut, that control cell migration. This will lead to an understanding of formation of the gut nerve system and of Hirschsprung's disease, at the population level, a level not well served by molecular levels of understanding. These models will have application in the many developmental contexts where cell movement and growth are simultaneous.Read moreRead less
The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack ....The immune system plays an important role in protecting us from infectious diseases. To do this it regulates a series of cell types that must decide upon an appropriate course. In general, this response is successful and protective. However, occasionally the cells make an inappropriate decision leading to problems. For example, allergies are an incorrect response against pollens and dust mites. Similarly, autoimmune disease such as diabetes and multiple sclerosis result from inappropriate attack upon our own tissues. Despite the clear importance of immune regulation for health, the number of different cell types involved and the complexity of their behaviour has made it difficult to predict and control the response. In this research program a new theory of immune regulation enables the reduction of the complex system to separate components that can be modelled by computer to predict the outcome. An improved predictive framework promises to have a major effect on our understanding and ability to control immune related diseases.Read moreRead less
Lipoprotein Metabolism And Mutations Of The APOB Gene Causing Familial Hypobetalipoproteinaemia
Funder
National Health and Medical Research Council
Funding Amount
$396,179.00
Summary
Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and ear ....Cardiovascular disease is an increasing problem in Australia, however, the cause of atherosclerosis is incompletely understood. A protein, known as apolipoprotein (apo) B, plays a central role in lipoprotein metabolism. Elevated levels of apoB are characteristic of many forms of hypercholestrolaemia. Familial combined hyperlipidaemia and polygenic hypercholesterolaemia are two common inherited disorders of lipoprotein metabolism that are characterised by elevated apoB levels in the blood and early atherosclerosis. In contrast, familial hypobetalipoproteinemia is a rare inherited disorder of lipoprotein metabolism characterised by very low levels of cholesterol and apoB in the blood and resistance to atherosclerosis and cardiovascular disease. The focus of this research project is to explore the regulation of apoB metabolism using individuals from unique families with familial hypobetalipoproteinaemia. First, we will determine and characterise the alterations in the APOB gene causing the low cholesterol levels in families with familial hypobetalipoproteinaemia. Second, we will determine if these apoB alterations affect the production and-or clearance of blood fats, or lipoproteins in affected individuals, when compared to controls, by performing metabolic studies. The proposed human in vivo metabolic studies will lead to a better understanding of the mechanism(s) involved in the assembly, secretion, transport, and clearance of plasma apoB-containing lipoproteins. Furthermore, these studies may reveal new protective mechanisms and potentially aid in the development of strategies to suppress over-production of apoB-containing lipoproteins in reciprocal conditions such as familial combined hyperlipidaemia or polygenic hypercholesterolaemia.Read moreRead less