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
Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and ....Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and cellular events associated with periodontal regeneration. Despite efforts to induce regeneration through the selective use of growth and differentiation factors it is becoming obvious that the most significant factor in successful clinical outcomes is the recruitment of special cells to the site of damage which have the potential to repair tissue damage. Thus, we intend to engineer different types of periodontal matrices in the laboratory and then transplant these newly formed tissues into sites affected by periodontal disease in an attempt to repair the damage caused by the disease process.Read moreRead less