Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Understanding Influenza Mortality And The Effects Of Vaccination In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$446,877.00
Summary
We will analyse mortality from influenza and other causes to estimate the numbers of deaths from other causes that are triggered by influenza in elderly persons, and to test the value of vaccination in preventing those deaths. Our results will help to decide whether an expensive clinical trial is really needed to show the benefit of influenza vaccination on all-cause mortality in the elderly.
Dynamic Aspects Of Inhibitory Synaptic Transmission And Modulation By Neuroactive Drugs
Funder
National Health and Medical Research Council
Funding Amount
$370,500.00
Summary
Information moving through the brain is typically encoded as brief bursts of signals. These signals travel along the microscopic wiring that connect the brain's nerve cells into complex circuits. Information is encoded in the frequency of the signals within a burst, and the duration of each burst. This frequency-coded information is processed at the contact points between nerve cells (synapses). Almost all neuroactive drugs target synapses, where they alter information processing. Most of the in ....Information moving through the brain is typically encoded as brief bursts of signals. These signals travel along the microscopic wiring that connect the brain's nerve cells into complex circuits. Information is encoded in the frequency of the signals within a burst, and the duration of each burst. This frequency-coded information is processed at the contact points between nerve cells (synapses). Almost all neuroactive drugs target synapses, where they alter information processing. Most of the information about how neuroactive drugs work has been acquired from experiments performed under steady-state conditions. Typically, drugs are applied at a constant concentration and a synapse is stimulated at an unrealistically low frequency. The data obtained under these conditions are very useful, but tell only part of the story. For example, during an extended burst of signals, some neuroactive drugs may be displaced from their synaptic binding sites, reducing their effectiveness. In contrast, other drugs can only bind when synapses are active, and their effectiveness will increase during a burst of signals. For optimal drug design and delivery, it is important to understand how drugs work during bursts of activity. To date, the highly dynamic, non-equilibrium conditions encountered at central synapses have not been extensively studied. The central goal of this research proposal is to investigate the dynamic properties of synapses, and the drugs that modulate them. The results will provide insights into information processing in the brain, and will have significant implications for the development and targeting of clinically relevant neuropharmacological compounds.Read moreRead less
The Kynurenine Pathway Chemokines And MIC-1 In The Pathogenesis Of AIDS Dementia Complex.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
This proposal will examine the mechanisms by which HIV and other brain disorders such as encephalitis damage the brain. Further understanding of the biochemical pathway involved will lead to the possibility of novel drug therapy for these disorders.
The Role Of Interferon Signalling In The Regulation Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
This project focuses on the role that inflammation plays in the progression of the type of neural injury seen in stroke victims. This project targets a specific pathway that is thought to be involved in the regulation of general inflammation but has not been greatly investigated in terms of the neural injury seen in stroke. Understanding the actions of this pathway may lead to future therapies that can be used to prime the brain to react in a positive way to stroke.
The Effect Of Smoking On The Exacerbation Of Stroke: Oxidative Stress Involvement And Cerebrovascular Response.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
This grant addresses whether smoking contributes to the severity of stroke outcome. The studies outlined in this proposal will contribute significantly in our understanding of how smoking contributes to the progression of stroke. The understanding of the involvement of smoking in the progression of stroke will be of great benefit in the development of improved stroke patient management.
A reduced capacity to recover balance following an imbalance episode contributes to the high incidence of falls in older adults. The goal of the present study is to determine how age-related differences in lower extremity neuromuscular and biomechanical properties are related to balance recovery capacity and falls incidence. A detailed understanding of this relationship is necessary for the development of efficacious exercise-based interventions for the prevention of falls.