House Dust Mites, Endosymbiotic Bacteria And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$208,372.00
Summary
Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) ....Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) and allergy to it has been shown to be an independent risk factor. Our laboratory has been involved in these studies and have isolated several enzymes associated with digestion. We have also shown that the mite proteases are potent inducers of cytokines from respiratory epithelium, indicating that the biochemistry of allergens may be important in the sensitisation. During these studies, we have shown that mites produce enzymes which lysed Gram-positive bacteria. Analysis of one of these enzymes has revealed that mites are colonised by bacteria in their gut. These bacteria may well be a source of some of the allergens which provoke symptoms in asthmatic patients. In this grant proposal, experiments will be performed to assess this possibility. Such findings may have significant impact on our understanding of mite allergy as well as highlighting potentially new insights into mite control.Read moreRead less
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