Regulation Of Platelet Adhesion By The GPIbalpha Cytoplasmic Tail
Funder
National Health and Medical Research Council
Funding Amount
$516,014.00
Summary
Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood ....Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important deteminant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis). A better understanding of these processes will add significantly to our knowledge of how blood clotting is controlled. This information is relevant to many human diseases including heart attack and stroke.Read moreRead less
Evaluation Of Factor Va From The Venom Of The Australian Brown Snake As A Topical And Systemic Anti-bleeding Agent
Funder
National Health and Medical Research Council
Funding Amount
$113,742.00
Summary
Anti-bleeding agents are important pharmaceuticals for use in truama, surgery and several medical conditions to reduce blood loss and the need for blood transfusion. Some Australian snakes contain in their venom a powerful blood clotting agent. This agent mimics the human clotting machinery. In this project, we plan to test purified components of snake venom for an ability to clot human blood. We will undertake laboratory test-tube experiments as well as using an animal model after ethical appro ....Anti-bleeding agents are important pharmaceuticals for use in truama, surgery and several medical conditions to reduce blood loss and the need for blood transfusion. Some Australian snakes contain in their venom a powerful blood clotting agent. This agent mimics the human clotting machinery. In this project, we plan to test purified components of snake venom for an ability to clot human blood. We will undertake laboratory test-tube experiments as well as using an animal model after ethical approval. This project seeks to capture some of the genetic blueprint of an Australian snake, for human benefit by developing a new therapeutic agent based on a venom component. If the experiments are successful, the next stage will be further testing of efficacy and toxicity before seeking approval for clinical trials. The research is supported by the Australian pharmaceutical company QRx Pharma Pty Ltd who will work with Uniquest Pty Ltd to protect intellectual property generated in the project.Read moreRead less
Development Of A Novel Orally Active Peptide For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$402,145.00
Summary
Chronic pain from damage to the nervous system is difficult to treat. A new type of drug has recently been developed from sea snail venom to treat chronic pain but is given by injection, which limits its use. Our research has developed a stable molecule that has analgesic activity when ingested. This proposal focuses on further testing to fully establish this molecule's therapeutic potential. This information can then attract a commercial partner to bring the new drug into general use.
Investigation Of The Role Of The GPIb/V/IX-filamin-1 Interaction In Regulating Platelet Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important determinant not only in norm ....Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important determinant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis) associated with the development of diseases such as heart attack and stroke. Our particular focus is on the interaction between adhesion receptors on the surface of the platelet and components of the intracellular platelet structure referred to as the cytoskeleton and how this interaction might regulate the reactivity of platelets and their ability to adhere to blood vessels. We believe this may be an important mechanism that regulates platelet adhesion and notmal blood clotting.Read moreRead less
Dissecting The Divisome: Development Of Antibacterial Agents That Inhibit Bacterial Cytokinesis
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
Infectious diseases accounted for 25-30% of the estimated 54 million deaths worldwide in 1998. Unfortunately, the recent spread of antibiotic resistant bacteria from hospitals into the community has coincided with a marked downturn in the rate of development of new antibiotics. Thus, there is an urgent need to develop new antimicrobial agents. The aim of this project is to provide essential groundwork for the development of new antimicrobials that inhibit bacterial cell division.
Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Several peptides derived from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. One of these, conotoxin MVIIA, has recently been approved in the US and Europe and others, including CVID and ACVI, are in various stages of clinical investigation. These small disulfide rich peptides share the attractive features of peptid ....Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Several peptides derived from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. One of these, conotoxin MVIIA, has recently been approved in the US and Europe and others, including CVID and ACVI, are in various stages of clinical investigation. These small disulfide rich peptides share the attractive features of peptides in general of having exquisite selectivity for particular receptors, but also share the general disadvantages of peptides of short biological half-lives and poor bioavailablility. Stabilisation of these conotoxins has the potential to substantially increase their therapeutic potential. In preliminary studies we have shown that by introducing a circular petide backbone into a conotoxin using a linker sequence we can increase its stability and resistance to enzymatic degradation. We therefore propose that it will be possible to cyclise a wide range of conotoxin molecules and thereby improve their drug like properties. In this project we will use our cyclisation approach to develop new potential treatments for pain from two classes of conotoxins. One of the lead molecules shows oral bioavailability in an animal pain model and potentially represents a major breakthrough in the field of peptide drug delivery.Read moreRead less
I am a structural biologist specialising in nuclear magnetic resonance spectroscopy who is primarily studying the properties and applications of proteins and peptides in drug design.
New Peptide-based Drugs For The Treatment Of Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$527,171.00
Summary
Chronic pain affects 1 in 5 Australians and neuropathic pain is among the most severe forms of chronic pain. Peptides from cone snail venoms have attracted recent attention as potential therapeutic agents for the treatment of neuropathic pain. Unfortunately, these peptides suffer from the disadvantage of short biological half-lives and poor activity when taken orally. We have developed a new approach to solve these problems that we will apply to develop new drugs for the treatment of pain.