Functional MRI And MR Spectroscopic Studies Of Penicillin Induced And Kindled Sheep Models Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$311,244.00
Summary
Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new techni ....Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new technique which may improve our ability to localize the seizure focus from which seizures arise, if the brain can be imaged at, or near, the time of a seizure. MR spectroscopy (MRS) enables us to detect metabolic changes in the brain which may persist at the site where seizures have begun for up to 30 minutes after the seizure. The aim of our research is to obtain a greater understanding of the changes detected with these MR modalities so that we can learn to apply these techniques to human sufferers of epilepsy. Ultimately it may help enable previously incurable epilepsy patients to undergo successful surgery and live normal lives.Read moreRead less
Beta-lactamase Mediated Antibiotic Resistance In Gram-negative Pathogens: How Does Genotype Relate To Phenotype?
Funder
National Health and Medical Research Council
Funding Amount
$397,869.00
Summary
Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expressio ....Unfortunately, one of the consequences of antibiotic usage (and in particular over-use and mis-use) is the development of resistance; if a small proportion of bacteria survive treatment, they can grow and replace the previous population of sensitive bacteria. In addition, the genes that confer resistance can be transferred between different bacterial lineages, thus facilitating the dissemination of resistant bacteria. The most important mechanism of penicillin resistance is through the expression of an enzyme called a beta-lactamase. This enzyme breaks down the penicillin. Beta-lactamase enzymes come in many different varieties, and new varieties appear quite frequently. Remarkably, when new kinds of penicillin are invented to circumvent resistance, the appearance of new beta-lactamases that can break down these new penicillins follows shortly thereafter. The objectives of our research are twofold. Firstly, it is now clear that the relationship between the beta-lactamase genes in a bacterium and the resulting pattern of resistance can be very complex. It can involve both the broad nature of the genes, the numbers of duplicates of the genes inside the cell, and very minor changes to the gene sequences. We will probe the relationship between the gene and resistance so as to understand it at a deeper level. Secondly, we will use this information to develop very efficient and cost affective methods for keeping track of the spread of the different varieties of beta-lactamase genes. These methods will be designed to be carried out on real-time PCR machines. These high-tech devices are general purpose gene analyzers that can carry out many different kinds of genetic assay. They are rapidly becoming ubiquitous in clinical microbiology laboratories. The use of these methods will provide much hard information that will be used to minimise the dissemination of antibiotic resistance.Read moreRead less
How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
Therapeutic Strategies In Epithelial Cancer Through Signalling Inhibition Of The Epidermal Growth Factor Receptor.
Funder
National Health and Medical Research Council
Funding Amount
$136,250.00
Summary
The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that ....The growth of cancer cells is regulated by many factors, including the presence of growth receptors on the surface of cancer cells. The epidermal growth factor receptor (EGFR) is present in some normal tissues, but is highly expressed on many common cancers, including brain, breast, lung, head and neck, colon and prostate cancer. We are developing a number of potential therapeutic compounds that act by inhibiting the EGFR in cancer cells. These compounds include a novel monoclonal antibody that binds to EGFR and inhibits its function, and a small molecule that binds to a portion of the EGFR inside cancer cells and also inhibits function. Both of these compounds prevent tumour growth in laboratory studies. This project will examine the mechanisms of action of these compounds, and explore ways to improve their anti-cancer effect. We have also shown that combining these compounds with other therapeutics eg chemotherapy markedly enhances their anti-cancer effect. We will further examine the mechanisms of these effects, and also determine if radiotherapy has additive anti-cancer effects. These studies will provide a basis for improved therapies for cancers overexpressing the EGFR.Read moreRead less
Health Services Research: A Randomised Controlled Trial To Evaluate A Model Of Comprehensive Stroke Care
Funder
National Health and Medical Research Council
Funding Amount
$519,150.00
Summary
This study compares the length of stay and patient outcomes between two stroke care models - co-located acute-rehabilitation and dislocated acute-rehabilitation stroke care. In participating hospitals, acute stroke patients admitted to the emergency department will be randomly allocated to either model of care. Length of hospital stay and clinical outcomes will be examined 90 days post-stroke. Study results will provide high level of evidence for future stroke care model development.