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.
Mechanisms Underlying The Biochemical Activity Of Scabrosin Esters And Other Epipolythiodioxopiperazine Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$256,527.00
Summary
Fungi produce a variety of chemicals which are toxic to animals. The fungi have probably developed the ability to synthesize and secrete these toxins as part of a chemical defence mechanism and-or in order to limit other microbial life forms because of nutrient competition. Some of these toxins will selectively kill microbes such as bacteria and other fungi as well as simpler life forms such as viruses, which can cause pathological changes to human beings. Fungal toxins may also be useful for co ....Fungi produce a variety of chemicals which are toxic to animals. The fungi have probably developed the ability to synthesize and secrete these toxins as part of a chemical defence mechanism and-or in order to limit other microbial life forms because of nutrient competition. Some of these toxins will selectively kill microbes such as bacteria and other fungi as well as simpler life forms such as viruses, which can cause pathological changes to human beings. Fungal toxins may also be useful for control of proliferative diseases such as cancer. Because fungi have had many millions of years to select for the most efficient toxins, they have been a valuable source of potent toxins for study. Some of these toxins are now in use clinically to treat human diseases ie penicillin and cyclosporin A. A fundamental understanding of fungal toxins is important to ensure the availability of new drugs to combat resistant strains of bacteria and to provide clues for the synthesis of new drugs to treat cancer which can also develop resistance to currently used drugs.Read moreRead less
Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make ....Snapshots of an enzyme in action: structural and mechanistic studies on the catalytic cycle of Escherichia coli ketol-acid reductoisomerase. Enzymes are required for almost every process that occurs in a living organism. For this reason, understanding how enzymes work is essential if we are to understand life itself. In this project we will investigate the enzyme KARI by capturing a series of snapshots of its atomic structure as it progresses through its working cycle. In addition, we will make a series of small alterations to the atomic structure that will allow us to understand how the individual parts work together.Read moreRead less
Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds ....Structure and inhibition of acetohydroxyacid synthase. Acetohydroxyacid synthase (AHAS) has been identified as the target for several widely used herbicides known as the sulfonylureas and imidazolinones. World-wide, these two herbicides account for $US2 billion in annual sales. The aim is to determine the three-dimensional structure of AHAS from several sources and in complex with these herbicides. Furthermore, AHAS appears to be an excellent target for the development of antibacterial compounds and fungicides. Knowledge of the three dimensional structures of these enzymes will be important in the rational design of more effective inhibitors with improved selectivity.Read moreRead less