Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies i ....Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies into clinical practice.Read moreRead less
PRE CLINICAL TRIAL WITH FETAL PIG INSULIN-PRODUCING CELLS
Funder
National Health and Medical Research Council
Funding Amount
$292,416.00
Summary
If fetal pig cells are to be of value in normalizing blood glucose levels in diabetic people once transplanted, they must survive and mature after being grafted. The pre-clinical study proposed will examine several novel issues that are of direct relevance to future clinical trials. The diabetic pig will be used as recipient to address when the fetal cell matures after it is transplanted, how long the grafted cells will maintain normal blood glucose levels, and at which site it is most appropria ....If fetal pig cells are to be of value in normalizing blood glucose levels in diabetic people once transplanted, they must survive and mature after being grafted. The pre-clinical study proposed will examine several novel issues that are of direct relevance to future clinical trials. The diabetic pig will be used as recipient to address when the fetal cell matures after it is transplanted, how long the grafted cells will maintain normal blood glucose levels, and at which site it is most appropriate to transplant the cells. The baboon will be used as recipient to address the safety of transplanting the pig cells, especially from the pig endogenous retrovirus, and whether the immunosuppressive regime proposed for use in humans will prevent cellular rejection. The diabetic baboon will be used in the final experiment step to determine if normalization of blood glucose levels can be achieved in this xenografted animal just as it can in the diabetic pig.Read moreRead less
Molecular Determinants Of UDP Glucuronosyltransferase Expression In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The gastrointestinal tract is a major portal of entry for dietary chemicals and drugs taken orally or as suppositories. Enzymes resident in the gastrointestinal tract have an essential role in preventing these chemicals from reaching other organs and target tissues in the body and in protecting the gastrointestinal tract per se from their effects. The levels of these enzymes in the gastrointestinal tract varies quite extensively between individuals. In this project we will determine how these en ....The gastrointestinal tract is a major portal of entry for dietary chemicals and drugs taken orally or as suppositories. Enzymes resident in the gastrointestinal tract have an essential role in preventing these chemicals from reaching other organs and target tissues in the body and in protecting the gastrointestinal tract per se from their effects. The levels of these enzymes in the gastrointestinal tract varies quite extensively between individuals. In this project we will determine how these enzymes are regulated and what causes the large differences in their levels between individuals. This will help us to predict those individuals who are more at risk from the adverse effects of drugs taken orally or as suppositories and from the toxic effects of chemicals in the diet. The project will also help us identify therapies that can increase the levels of these protective enzymes to help reduce the effects of exposure to toxic chemicals .Read moreRead less
Characterization Of Novel Human UDP Glycosyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$417,750.00
Summary
Our defense against the toxic effects of small organic molecules is mediated by families of enzymes found in the internal membranes of cells, predominantly in the liver and gastrointestinal tract. Many small organic molecules, such as environmental pollutants, carcinogens and therapeutic drugs, are fat-soluble and will accumulate in the body to toxic levels unless they are modified by the addition of water-soluble groups. The modified chemical, in the majority of cases, is less toxic and readily ....Our defense against the toxic effects of small organic molecules is mediated by families of enzymes found in the internal membranes of cells, predominantly in the liver and gastrointestinal tract. Many small organic molecules, such as environmental pollutants, carcinogens and therapeutic drugs, are fat-soluble and will accumulate in the body to toxic levels unless they are modified by the addition of water-soluble groups. The modified chemical, in the majority of cases, is less toxic and readily removed from the body. One aim of this project is to identify and characterize newly discovered enzymes in the family that uses sugar residues to modify and eliminate fat-soluble chemicals. Their involvement in the detoxification process and how they are controlled in the cell will be determined. These are the final enzymes in this family remaining to be characterized in humans. In addition to foreign chemicals and toxins, this enzyme family also regulates the intracellular concentrations of signalling molecules such as steroid hormones and chemicals that bind to gene regulatory proteins. Defects and-or variations in these enzymes may alter the levels of these signalling molecules and lead to uncontrolled cell growth (cancer) or cell death. A second aim of this project is to determine whether these novel enzymes are involved in controlling signal concentrations and to determine whether inherited variations in these enzymes will alter the signalling process.Read moreRead less
Representation Of Spatial Coordinate Systems Within Posterior Parietal Cortex And Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$43,759.00
Summary
To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the ....To accurately reach for an object or walk from one room to another, our brains need to be able to locate objects around us and detect obstacles in our path. Our amazing ability to make an accurate eye movement directly towards an object such as a cup of tea and move our hand smoothly and directly to the cup is something we all take for granted. However, this ability requires enormous computational complexity which our brains have evolved to handle with ease. We plan to determine the parts of the brain that perform these computations by using a relatively new technique called functional magnetic resonance imaging or fMRI. This is a non-invasive technique that requires a person to lie in an MRI scanner and perform simple eye movement tasks while the scanner takes images of the brain. With this technology we are able to determine which regions of the brain are most active during the performance of each task, thereby giving us an insight into how the brain works. An area of the brain called the parietal lobe is thought to be involved in the localization of objects, such as reaching for a cup of tea. We will study this area using fMRI to determine how a map of space is represented within the parietal lobe. This region of the brain communicates with another region, the hippocampus which is thought to be involved in navigation, such as walking about the house or driving in the city. Functional MRI will be used to study the hippocampus of our subjects while they perform simple navigational tasks through a maze which is simulated on a computer screen. This will reveal the role hippocampus plays in navigation and the relationship between the parietal lobe and hippocampus. We hope that the greater understanding of hippocampus that will arise from this study will enable us to devise a robust method for imaging hippocampal function with fMRI. We expect that these techniques will aid in the diagnosis of hippocampal abnormalities in patients with temporal lobe epilepsy.Read moreRead less