Structural Diversity And Evolution Of Variant-specific Surface Proteins In The Protozoan Parasite, Giardia
Funder
National Health and Medical Research Council
Funding Amount
$436,417.00
Summary
Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect ....Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect the parasites against digestion, enabling them to reside indefinitely within the intestine. However, the proteins are also the principal target of host immunity. Analysis of Giardia populations has shown that as many as 150-200 different coat proteins can be made. Although individual cells have coats comprised of only a single protein type, these can 'switch' spontaneously to production of another type - a phenomenon known as 'antigenic variation'. This process occurs slowly but continuously, giving rise to 'variants' which survive successive host responses (directed against each predominant coat type) and occupy the vacancies left by the destruction of their immediate forebears. It is important to gain information about the structural diversity of these variant-specific proteins (VSP), as any 'Giardia' vaccine is likely to require inclusion of each major type. It is also important to elucidate how the 'switching' process occurs, as this may provide clues as to how it might be interrupted. The project addresses both aspects.Read moreRead less
Epigenetic Control Of Antigenic Variation In Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$505,563.00
Summary
Malaria is an enormous global health problem that kills millions of people each year. Humans develop only partial immunity to malaria only if they survive many years of repeated infection. Much of the difficulty in developing immunity to malaria lies in the ability of the causative agent, Plasmodium falciparum, to continually change the properties of its surface coat. The parasite achieves this immune evasion through a process called antigenic variation. Genetically identical parasites can expre ....Malaria is an enormous global health problem that kills millions of people each year. Humans develop only partial immunity to malaria only if they survive many years of repeated infection. Much of the difficulty in developing immunity to malaria lies in the ability of the causative agent, Plasmodium falciparum, to continually change the properties of its surface coat. The parasite achieves this immune evasion through a process called antigenic variation. Genetically identical parasites can express different surface coats, and the control of this process is superimposed above the level of genetic control. This system is referred to as epigenetic control. Epigenetic control includes regulatory mechanisms such as the way that genes are packed inside the parasite, and chemical modifications to the proteins (called histones) around which genes are wrapped. We wish to understand the epigenetic control system that the parasite uses to orchestrate the phenomenon of antigenic variation. We will use two methods to gain this understanding; the first is a genetic screen that will create mutations in the parasite using jumping DNA (called transposons) that will break down the control mechanism behind antigenic variation. Identifying the mutated genes will show us which genes organize antigenic variation in normal parasites. Our second approach is to genetically knockout parasite genes that are related to the genes that govern epigenetic mechanisms in other, better understood organisms like humans and yeast. We will test the effect of these targeted gene deletions to discover which of these genes are involved in regulating antigenic variation. The insights gained from these discoveries will improve our understanding of how the malaria parasite evades our immune system. A better understanding of this immune evasion may help us to understand how to build better vaccines against malaria.Read moreRead less
Characterisation Of Antigenic Variation Of Neisserial Cell Surface Adhesins, And Their Role In Infection
Funder
National Health and Medical Research Council
Funding Amount
$556,983.00
Summary
A group of bacteria called Neisseria cause human-specific infections. They produce two types of surface proteins termed adhesins, which allow the bacteria to adhere to, and invade, human cells. There is circumstantial evidence to suggest the bacteria can rapidly vary the structure of these adhesins, even within a single infection. This project will determine whether, and how, this variation is occurring, and what effect it has on the ability of the bacteria to cause disease.
NATIONAL TRENDS IN SUICIDE BY AGE, GENDER, GEOGRAPHY, SOCIO-ECONOMIC AND MIGRANT STATUS AND MENTAL HEALTH
Funder
National Health and Medical Research Council
Funding Amount
$148,690.00
Summary
Suicide in Australia has become an increasingly important public health problem, chiefly because of increasing rates in some population sub-groups, and to a lesser extent because declines in other external causes of death have increased the prominence of suicide. Since the 1970s suicide rates have increased in young males and have eclipsed motor vehicle accidents as the dominant cause of death in this group. Suicide in the young produces a significant impact on years of life lost from premature ....Suicide in Australia has become an increasingly important public health problem, chiefly because of increasing rates in some population sub-groups, and to a lesser extent because declines in other external causes of death have increased the prominence of suicide. Since the 1970s suicide rates have increased in young males and have eclipsed motor vehicle accidents as the dominant cause of death in this group. Suicide in the young produces a significant impact on years of life lost from premature mortality. Suicide rates have been shown to vary by socio-economic status, ethnicity, area of residence, age and sex. In NSW for example, suicide rates in young males have been found to have increased by 50% in urban areas, and by 5-6 times in isolated rural areas. Another study has shown suicide rates to vary by country-of-birth which in turn has an effect on its relationship with socio-economic status. However, not all studies have replicated findings in NSW. In Queensland, for example, it has been shown that male youth suicide rates in rural areas have not substantially exceeded those in urban areas. There have been very few studies at the national level of variations in suicide in Australia. Most studies of Australian suicide to date have been confined to state-level analyses or to very limited nation-level analyses. An additional spur to a whole-nation approach to suicide has been the nation-wide Australian Bureau of Statistics Mental Health and Wellbeing Profile of Adults and a similar mental health survey of youth. Thus for the first time it will be possible to relate population prevalence of self-reported mental illness to suicide rates. In short, the current proposal addresses the two major gaps in Australia in population suicide research: examining suicide at the national level with regard to geographic location, immigrant and socio-economic status; and correlating surveyed prevalence of mental illness with suicide rates.Read moreRead less