Virus Vaccines That Ensure Preparedness Against Future Public Health Emergencies
Funder
National Health and Medical Research Council
Funding Amount
$862,061.00
Summary
In this proposal, we will utilize novel technology we have developed (the molecular clamp) to generate candidate subunit vaccines and therapeutic antibody treatments against four highly pathogenic viruses identified by the World Health Organization as requiring urgent R&D to prepare for future epidemics; Ebola virus, Middle East Respiratory Coronavirus, Nipah virus and Lassa fever virus. Resulting vaccines are expected to provide advantages including safety, efficacy, and thermal stability.
Cell-cell fusion is critical for the development and transport capacity of the placenta during pregnancy. Impairments in this process occur in pregnancy complications such as preeclampsia (PE). We have identified a novel pathway (LY6E) regulating placental cell-cell fusion which is also dysregulated in human pregnancies complicated by PE. In the current proposal we will investigate the mechanisms by which LY6E mediates cell-cell fusion and examine its role in the development of PE.
The neuronal synapse is very tightly regulated by proteins that control both the timing and the amount of neurotransmitter release and neuronal stimulation. Defects in this synaptic signal are linked to diseases including epilepsy, autism and dementia. In this study we will determine the molecular details of how proteins called SNAREs control neurotransmission in the human brain.
Hepatitis C virus (HCV) and Human immunodeficiency virus (HIV) infect 200 million and 50 million people world-wide, respectively, and there are no preventative vaccines. The work outlined in this fellowship seeks to understand the structure and function of the major surface proteins of these viruses, their ability to be recognised by the immune system and to develop a novel vaccine for the prevention of HCV.
Activation Of The Respiratory Syncytial Virus Fusion Protein
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Respiratory Syncytial Virus (RSV) is the most important viral cause of respiratory tract disease in both infants and the elderly. However, there are few available options for control, whether by vaccination or therapeutic intervention. This proposal investigates the way RSV infects cells. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can block this process and new insights for the generation of vaccine candidates.
Molecular Characterization Of Dengue Virus Fusion And Antiviral Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$573,557.00
Summary
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries around the world, including Australia. Infection with dengue viruses cause severe and sometimes fatal disease. This proposal focuses on the way dengue virus enters cells and the development of drugs that will prevent virus entry. We have already identified compounds that inhibit the entry process of dengue into cells and this project will significantly build on these early findings.
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infectio ....Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infection has increased steadily. More than 40% of the world's population is at risk of infection and this number is expected to increase as more people travel. This proposal focuses on the way dengue virus enters cells, specifically the mechanism used by viral proteins to mediate fusion of the viral membrane with that of the host cell. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can bind and block this process. In addition, we will also use this information in the design and generation of new vaccine candidates.Read moreRead less
Mitochondria are both the powerhouses and the poison cupboard of our cells. They have evolved from bacteria and still possess the ability to grow and divide. Unregulated mitochondrial division is seen in dying cells and in cells from patients with neurodegenerative diseases. We have identified new molecules involved in mitochondrial division and are investigating how they function in normal and unhealthy cells.
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less