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Using Metagenomics To Determine The Causative Agent(s) Of Tick-Borne Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$639,428.00
Summary
Tick-borne disease has emerged as a topical and controversial public health problem in Australia. We will employ state-of-the-art techniques in metagenomics to determine what microbial species (bacteria, viruses and eukaryotes) circulate in Australian ticks and whether these or different microbes are also present in humans diagnosed with tick-borne disease. The data generated will provide key information on whether tick-borne disease has a microbiological cause and, if so, the microbes involved.
The Role Of Paramyxovirus P Protein Subcellular Trafficking In Virus Pathogenicity And Antagonism Of Host Interferon Responses
Funder
National Health and Medical Research Council
Funding Amount
$78,491.00
Summary
Emerging zoonotic viruses pose a major health threat worldwide, highlighted by recent outbreaks of viruses such as Nipah and Hendra via interspecies invasion to infect humans. A major barrier to interspecies infection is the innate immune response, which viruses must evolve to combat before successful infection can occur. We aim to examine in detail the mechanisms underlying immune evasion of such viruses, with the ultimate goal of discovering novel targets for therapeutics to viral infection.
The balance between cellular survival and death must be tightly regulated. Cells respond to viral infection by self-destructing, thus limiting viral spread to other cells. Viruses have evolved ways to subvert this defensive cell suicide. This project will define and characterise viral factors that maintain host cell survival during infection. These may be targets for the development of new anti-viral therapies and vaccines.
Comparative Pathophysiology And Clinical Epidemiology Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$267,172.00
Summary
The simian parasite P. knowlesi is the most common cause of malaria in Malaysia and can cause severe and fatal disease. We are currently conducting a study of all malaria patients admitted to a tertiary referral hospital in Sabah, Malaysia. This will allow us to describe the epidemiological and clinical features of the hospitalised patients, including changes over time. We are also conducting novel pathophysiological studies which will allow us to understand how P. knowlesi causes sever disease.
Molecular Typing Of Salmonella Enterica Serovar Typhimurium
Funder
National Health and Medical Research Council
Funding Amount
$272,545.00
Summary
Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subd ....Salmonella mainly causes food poisoning and is a significant human health problem. Different Samonella forms are identified by serotyping and many serovars have been given a name . There are more than 2000 serovars. The best known serovar is Typhimurium which is the cause of 40% of salmonella infections. Typhimurium is so frequently involved in infections it is necessary to further divide it for outbreak investigations and long term monitoring of the organism. The only widely used method to subdivide Typhimurium is phage typing, which is done only in major laboratories (2 in Australia). Phage typing is based on lysis patterns of a test isolate to a set of 34 phages. Phage typing has played a crucial role in tracking the organism, for example the emergence of a multidrug resistance new type (DT204c) in UK and US. The technique is simple but the problem is that reactions vary with slight change in conditions and scoring the reaction results is very subjective. We propose to replace the typing system with one based on the DNA method PCR, so it will be simple, fast and accurate. We will use a DNA fingerprinting technique called AFLP (amplified fragment length polymorphism) to find markers (DNA segments) that are specific to phage types and design PCR assays based on the markers we find. Such a typing system will retain the essence of phage typing by providing continuity of the valuable epidemiological database on phage types. Further the typing system could easily be expanded to accommodate any new types by finding more markers while the current phage typing system is very difficult to expand (last done in 1977 and is behind in our needs). This project will establish a general approach for designing typing systems based on molecular biology for other pathogens and could have a major impact on the surveillance of bacterial infections in the 21st century.Read moreRead less
Molecular Characterisation Of Host Cell Targets Of Human Pathogenic Viruses And Evaluating Their Potential As Novel Therapeutic Targets.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed t ....There are currently no therapeutics to treat victims of Hendra, Nipah or Rabies virus infections, which account for > 50,000 deaths/yr worldwide. Through not fully understood mechanisms, these viruses affect the functions of specific cellular proteins in order to inhibit the host immune system, a process essential to their pathogenicity. We aim to characterise the mechanisms underlying viral inhibition of host immunity and evaluate their potential as novel targets to develop urgently needed therapeutics against these deadly pathogens.Read moreRead less
Spatiotemporal Risk Assessment Of Emerging Infectious Disease Threats To Australia
Funder
National Health and Medical Research Council
Funding Amount
$641,204.00
Summary
Emerging infectious diseases (EIDs) such as dengue and influenza pose a constant and growing threat to Australians. We live in an increasingly connected world in which EIDs cross borders and oceans, carried by infected people or vectors. This research will build an evidence base for allocation of resources to surveillance and preventive health programmes aimed at mitigating the threat of EIDs, through identifying high-risk sources, routes of introduction, incursion locations and communities.
Platform FoR European Preparedness Against (Re-)emerging Epidemics- Australia
Funder
National Health and Medical Research Council
Funding Amount
$386,463.00
Summary
Infectious diseases rank high among the threats to human wellbeing and prosperity- globalisation, migration, tourism, intensive farming and changing climate enhance the likelihood of emergence of outbreaks of infectious disease. The optimal response to an emerging infectious disease requires the rapid acquisition of new knowledge. This project ensures that Australia can contribute to globally coordinated research that will meet the research challenge associated with any new pandemic infection.
The Pathogenesis Of Melioidosis: The Interaction Of Burkholderia Pseudomallei With Host Cells.
Funder
National Health and Medical Research Council
Funding Amount
$344,375.00
Summary
Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen a ....Melioidosis is an often fatal disease of mainly tropical Australia and SE Asia caused by a bacterium which is found in soil and water. Infection occurs via wounds or by inhalation. Melioidosis has recently become endemic in south-west Western Australia and south-eastern Queensland, and could represent an emerging disease worldwide. Melioidosis disproportionately affects Aboriginal Australians. Melioidosis has many forms including septicemia with damage to most organs, particularly lung, spleen and liver, acute localised suppurative infection and pneumonia. Melioidosis may also become latent, and later develop into an acute and fatal infection. It is important to understand, at the molecular level, how and why the causative bacterium is able to cause disease. Only with such an understanding can measures be undertaken to prevent the disease, or novel methods developed to control the disease. Colonisation of a host is a first step in the disease process for all bacteria which cause disease. Large protein molecules located on the surface of disease-causing bacteria are usually neccessary for colonisation of the host since they allow adherence to the surface of host cells. We have previously undertaken a basic study of adherence. This study will build on this research with the aim of identifying molecules which mediate adherence to host cells, using in vivo and in vitro methods, including the techniques of molecular biology. This study will inevitably lead to the development of vaccine candidates which is important to the management of melioidosis, particularly in high risk groups. It may also allow the development of novel antimicrobial compounds.Read moreRead less
A Comparative Study Of The Pathophysiology Of Severe Knowlesi And Falciparum Malaria
Funder
National Health and Medical Research Council
Funding Amount
$660,293.00
Summary
Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction a ....Plasmodium knowlesi causes monkey malaria, but has recently been found to infect humans resulting in severe disease and death similar to Plasmodium falciparum. Clinical features of severe P. knowlesi and how it causes complications are poorly described and understanding this could improve treatment and outcomes. In patients with P. knowlesi, we want to describe the clinical features, the ability to cause severe disease, and measure 1) markers of platelet activation and 2) capillary obstruction and red cell deformability,Read moreRead less