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Dengue Host-cell Signalling Interactions: Novel Insights And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Dengue is a virus transmitted by mosquitoes that occurs in many tropical and subtropical regions. Approximately 40% of the world's population is at risk of this infection. Sometimes it can be mild but it can lead to severe illness and death especially with second infections. The body produces a response that over-reacts to the virus in these severe infections. The project aims to understand why the body does this and what parts of the immune system are affected using a model in mice.
Host Cell Signalling During HTLV-1 Infection: Novel Insights And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$62,335.00
Summary
Human T-leukemia virus 1 (HTLV-1) establishes a life-long infection and causes cancer and immune dysfunction. This study aims to find a cure for HTLV-1 by inducing the specific death of infected cells using novel therapeutic drugs that target host cell death pathways. Dead infected cells are then naturally cleared from the system along with the viral infection. The impact of HTLV-1 infection on tuberculosis severity will also be examined.
Preventing Violence-related Deaths Among Individuals Exposed To The Criminal Justice System
Funder
National Health and Medical Research Council
Funding Amount
$88,502.00
Summary
Violence is a public health problem. People who have criminal justice contacts are more likely to die and violence-related deaths are common. Not much is known about these deaths. This research will examine the violence-related deaths among young people who have justice contacts in Queensland. It will also examine violence-related deaths among adults who have been in prison from 12 different countries. This is the first study to comprehensively examine violence-related deaths in this group.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Pro-apoptotic Therapies For The Treatment Of Mycobacterium Tuberculosis Disease And Latent Infection
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Programmed cell death has an important role in our ability to fight organisms. Upon infection, processes result in activation of death-inducing cascades, resulting in death of cell and pathogen. M. tuberculosis, an escalating health problem, has developed mechanisms to prevent this, leading to latency. This study, which uses mouse M.tb models, hypothesises that reversal of these mechanisms, using drugs currently in trial in leukaemia (ABT-737 & BV6), may lead to clearance of infection.
Regulation Of Extrinsic Death Pathways In Neutrophils
Funder
National Health and Medical Research Council
Funding Amount
$84,656.00
Summary
During infection, the lifespan of neutrophils normally increases despite an abundance of neutrophil death signals in inflamed tissues. Altered lifespan of neutrophils has been reported in diseases associated with influenza, Streptococcus, RSV and cytomegalovirus infection. Our research has discovered a relationship between the two dominant death pathways in neutrophils, indicating that alterations in one death pathway protect the neutrophil from death signals from the second death pathway.
Cell Survival Pathways As Potential Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$142,914.00
Summary
Cancer cells are characterised by their capacity for relentless growth, survival and evasion of cell death. This proposal will use patient derived xenograft models of primary breast cancer to test the hypothesis that addition of BH3-mimetics could improve response to anti-HER2 therapy. This technique involves transplantation of patient tumours into immune-compromised mice. This represents a useful method for testing new agents.
Novel Multi-Modality Assessment Of Arrhythmic Risk And Disease Progression In Repaired Tetralogy Of Fallot Undergoing Redo-Pulmonary Valve Surgery Using 4D Cardiac MRI Flow And High Density 3D Electro-Anatomical Mapping.
Funder
National Health and Medical Research Council
Funding Amount
$110,703.00
Summary
Sudden death from arrhythmia is the most common cause of death in adults with tetralogy of Fallot, a type of congenital heart disease. It has been shown that dangerous arrhythmias can be induced in almost half of these patients when severe pulmonary valve disease is present. Our study will evaluate the potential for arrhythmias both before and after pulmonary valve surgery, using MRI and electrophysiological testing, to determine if these patients require defibrillators.
Impact Of Renal Transplantation On Cardiac Arrhythmia Burden And Type And Risk Of Sudden Cardiac Death In Patients With Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$124,608.00
Summary
Patients with Chronic Kidney Disease are at high risk of sudden death. We aim to characterise the impact of renal transplantation on arrhythmia profile. This has the capacity to impact our understanding of arrhythmia type and mechanism in renal failure.
Prediction Of Ventricular Arrhythmias And Prevention Of Sudden Cardiac Death Following Revascularised Acute Myocardial Infarction.
Funder
National Health and Medical Research Council
Funding Amount
$117,270.00
Summary
Acute myocardial infarction (AMI) is a leading cause of death in Australia. Patients with coronary artery disease and impaired left ventricular function are at increased risk of heart failure, reinfarction and sudden cardiac death (SCD). This research will evaluate optimal methods to identify patients at risk for SCD following AMI using echocardiographic, MRI, and electrophysiological characteristics, and improve survival by early identification and management of these high-risk patients.