Substandard Bed Nets And Malaria: Causes, Impact And Solutions
Funder
National Health and Medical Research Council
Funding Amount
$827,057.00
Summary
Long-lasting insecticidal nets (LLIN) are a cornerstone of malaria control. LLIN undergo strict testing overseen by WHO and are subject to inspections prior to delivery to recipient countries. Despite this, we found that LLINs delivered to Papua New Guinea (PNG) between 2013 and 2019 were ineffective against malaria mosquitoes. Concurrently we observed a massive rise in malaria in PNG. This study is aimed at understanding the causes and impact of substandard LLINs on the global malaria burden.
In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
Transgenic Expression Of The EWS-WT1 Fusion Protein,inducing The Development Of Tumour That Replicates The Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,976.00
Summary
A genetic translocation encoding the EWS-WT1 fusion protein is found desmoplastic small round cell tumours. Our aim is to examine the effect of this protein in inducing tumour growth in tissue cell lines. A virus will then be used to introduce the genetic translocation into mice to examine the effect of this protein on tumour growth in a mammal, thereby serving as a 'solid tumour model' to try and identify therapeutic targets.
Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
The Role Of Clostridium Difficile Spore Interactions With The Host In Gastrointestinal Infection And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,467.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
The Impact Of Clostridium Difficile Infection And The Host Immune Response On Colonic Homeostasis And Regeneration.
Funder
National Health and Medical Research Council
Funding Amount
$932,212.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
The Role Of Clostridium Difficile Virulence Factors In Mediating The Host-pathogen Interactions That Lead To Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains cause disease and why they are more harmful, which is critical for the development of improved strategies for preventing and treating these infections.
The Role Of Clostridium Difficile Spore Surface Structures In Initiating Gastrointestinal Infection And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$467,556.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infection ....Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infections.Read moreRead less
Evaluation And Comparison Of Lentiviral And AAV Vector Mediated Gene Therapy For The Mucopolysaccharidoses
Funder
National Health and Medical Research Council
Funding Amount
$521,320.00
Summary
The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which preven ....The mucopolysaccharidoses are a group of inherited diseases that have profound consequences for affected individuals. They have pleiotropic effects and usually result in premature death. Although intravenous enzyme replacement therapy has been developed for a number of these disorders, this approach to therapy is invasive, very expensive, of limited efficacy, and is completely ineffective in treating brain pathology. The principal reason for this is the protected nature of the brain which prevents enzymes that are administered intravenously from entering. Therefore, alternative therapies must be considered in order to provide more effective therapy for the mucopolysaccharidoses, especially those that have significant brain pathology. Gene therapy is one such alternative therapy but this still faces the problem of introducing the therapeutic agent (in this case the gene encoding the requisite enzyme) into the brain. This project aims to provide a comparitive evaluation of two gene therapy vectors for their efficacy in treating all aspects of the pathology found in the mucopolysaccharidoses. Both vectors have the properties of being able to efficiently deliver genes to different cell types and result in the stable genetic modification of the target cell, making them ideal for long-term treatment. However, for effective gene therapy, significant and widely distributed gene delivery to the brain, as well as to other tissues, will be required. This project aims to compare the efficacy of these vectors in two different animal models of the mucopolysaccharidoses that exhibit a wide range of the clinical problems associated with these diseases, importantly including brain pathology.Read moreRead less