Pharmacological Characterisation Of Venoms From Australian Box Jellyfish
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Australian box jellyfish are responsible for many stings in Australia every year. Years of scientific research have gone into studying how these venoms work however, their mechanism of action is still unknown. Most of these venoms cause cardiovascular effects in envenomed people. Our aim is to isolate and characterise these toxins in the venoms, this will hopefully allow us to then isolate their mechanism of action. Thus allowing for better management of accidental human envenomings.
Anaphylaxis: Pathophysiology, Acute Management, Diagnosis And Immunotherapy.
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. This award will support research projects that aim to improve both the emergency care of this condition and subsequent immunotherapy (desensitisation) for people who experience anaphylaxis to insect sting. It will also support research to better understand anaphylaxis to antivenoms, which is a major problem worldwide, and to thus improve the treatment of snake, scorpion and spider envenoming.
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
Molecular Toxinology Of Australian Box Jellyfish Venoms
Funder
National Health and Medical Research Council
Funding Amount
$283,110.00
Summary
Box jellyfish are an ongoing cause of illness and death for coastal communities and tourist regions in northern Australia. As well as creating a significant medical problem, the resulting closure of beaches during boxjellyfish 'season' results in an enormous loss of tourism income and threatens Australia's reputation as a safe destination. The jellyfish venoms contain toxins with potentially lethal effects on humans. For the first time, using pure venoms derived from the specialised stinging cel ....Box jellyfish are an ongoing cause of illness and death for coastal communities and tourist regions in northern Australia. As well as creating a significant medical problem, the resulting closure of beaches during boxjellyfish 'season' results in an enormous loss of tourism income and threatens Australia's reputation as a safe destination. The jellyfish venoms contain toxins with potentially lethal effects on humans. For the first time, using pure venoms derived from the specialised stinging cells (i.e. nematocytsts), we will isolate and characterize the major toxins from four species of box jellyfish. Their mechanism of action will be determined and the effect of various treatments such as antivenom will be investigated. This will also lead to the discovery of toxins with potentially novel targets and modes of action and increase our understanding of proposed treatments and prevention of stings.Read moreRead less
A Randomised Controlled Trial Of Factor Replacement Therapy In Snake Bite Coagulopathy
Funder
National Health and Medical Research Council
Funding Amount
$715,730.00
Summary
This proposal seeks funding to undertake a controlled trial of clotting factor replacement in snake bite coagulopathy after the administration of a neutralising dose of antivenom. The aim is to determine if factor replacement will result in a rapid return of clotting function in patients and therefore reduce the potential risk of major bleeding. This study will have international implications because globally snakebite coagulopathy is a major cause of morbidity and death like in Australia.
Randomised Controlled Trial Of Intravenous Antivenom Versus Placebo In The Treatment Of Redback Spider Bite
Funder
National Health and Medical Research Council
Funding Amount
$487,440.00
Summary
Redback spiderbite is the most common significant envenoming in Australia and bites by the closely related widow spiders are a major global problem. Despite widespread use of redback spider antivenom, no controlled study has tested its effectiveness. This study aims to test the efficacy of antivenom versus placebo in a large multicentre, randomised controlled trial - RAVE-II. It is of critical importance to determine if an expensive treatment with a known risk of allergic reactions is effective.
Does Fresh Frozen Plasma In Russells Viper Bite Coagulopathy Reduce The Dose And Duration Of Antivenom Therapy?
Funder
National Health and Medical Research Council
Funding Amount
$622,344.00
Summary
This proposal seeks funding to undertake a trial of clotting factor replacement with low dose antivenom therapy in snake bite coagulopathy in Sri Lanka. The aim is to determine if factor replacement will result in a rapid return of clotting function, allow a smaller dose of antivenom and therefore reduce the potential risk of major bleeding and reactions to antivenom. This study will have international implications because globally snakebite coagulopathy is a major cause of morbidity and death .
Structural Studies Of Bacterial Pore-forming Protein Toxins
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
In this project the three-dimensional structures of proteins that form pores in membrane cell walls will be determined. These proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. This project will focus on a class of toxins called the cholesterol-dependent cytolysins which are released by Gram positive bacteria such as Clostridia and Streptococcus and which cause a variety of nasty infectious diseases such as gas gangrene, pneumonia an ....In this project the three-dimensional structures of proteins that form pores in membrane cell walls will be determined. These proteins are bacterial toxins and knowledge of their structure may prove useful in the design of new antibiotics. This project will focus on a class of toxins called the cholesterol-dependent cytolysins which are released by Gram positive bacteria such as Clostridia and Streptococcus and which cause a variety of nasty infectious diseases such as gas gangrene, pneumonia and meningitis. The three-dimensional structures will be elucidated using X-ray crystallography. Protein crystallography is the study of three-dimensional shapes of proteins at near atomic resolution. In this method proteins are made to form crystals. X-ray beams are then shone on the crystals causing the X-rays to scatter in a pattern which is characteristic of the protein's three-dimensional shape. Knowledge of the structure of proteins is necessary for the complete understanding of their biological activity and is also very useful for the rational design of new drugs that may alter their activity.Read moreRead less
A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on ....A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on pain research, the Program will significantly enhance the scope of existing multidisciplinary collaborations between the Cis Lewis Alewood, Adams and Christie, which have already made a considerable impact in the fields of pharmacology and neuroscience. The CIs also have considerable experience in the development of pain therapeutics, having discovered two conopeptides now under commercial development with AMRAD (AM336) and Xenome Ltd (Xen2174). This Program will discover and use highly selective conopeptides such as these to dissect the pharmacology of peripheral pain pathways and their projections into the central nervous system, and to identify and characterise new targets amenable to drug intervention. The long-term goal of the Program is to discover new targets in pain pathways and develop conopeptides that act on these targets in animal models of chronic pain. These molecules will be optimised within the Program to the point where they can be considered for pre-clinical development in collaboration with commercial partners.Read moreRead less