A Novel Physiological Role For Cytochrome P450 Enzymes In The Brain?
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
The cytochrome P450 enzymes in human liver have been traditionally regarded as drug metabolising enzymes. However, it is now becoming clear that they are distributed in other tissues in the body and that they may serve important and diverse roles in normal physiology. Little is known about their functions in the brain. We have identified a reaction catalysed by these enzymes that generates a chemical found in the brain normally, whose levels are elevated under stress and which, when given to ani ....The cytochrome P450 enzymes in human liver have been traditionally regarded as drug metabolising enzymes. However, it is now becoming clear that they are distributed in other tissues in the body and that they may serve important and diverse roles in normal physiology. Little is known about their functions in the brain. We have identified a reaction catalysed by these enzymes that generates a chemical found in the brain normally, whose levels are elevated under stress and which, when given to animals, is anxiogenic. This points to a possible involvement of P450 enzymes in a hitherto unexplored branch of the stress response. Importantly, it may lead to the development of novel drugs that block the P450 and therefore block production of the anxiogenic chemical. This proposal is designed to explore the basic biology underlying this system.Read moreRead less
The Utility Of Genomics And Functional Imaging To Predict Irinotecan And Sunitinib Pharmacokinetics And Pharmacodynamics
Funder
National Health and Medical Research Council
Funding Amount
$815,733.00
Summary
Cancer patients have large differences in the way their liver breaks down anticancer drugs, leading to a poor tumor response or severe side effects. This project will be with 2 cancer drugs which can cause severe side effects. Patients will have special liver Xrays to check their liver function and have blood taken to look at DNA or genes important in drug breakdown and action. These genes and imaging may help identify patients at risk of severe toxicity or poor response and optimise drug use.
Unique Isoform-specific Regulation Of Cardiac Ryanodine Receptors By Calcium Store Proteins
Funder
National Health and Medical Research Council
Funding Amount
$421,160.00
Summary
The importance of proteins that regulate calcium stores of heart muscle is graphically illustrated by massive changes in cell structure and function, which lead to ventricular fibrillation and fatality when the proteins are disrupted. We recently made the remarkable discovery that the proteins have a unique action in the heart which enhances cardiac contraction. We will discover the interaction sites between the proteins and will define novel therapeutic targets for heart failure.