Investigating The Biological Significance Of Proteolytic Prion Protein Processing.
Funder
National Health and Medical Research Council
Funding Amount
$328,558.00
Summary
Prion diseases, including Bovine Spongiform encephalopathy (“mad cow disease”) and Creutzfeldt-Jakob Disease in humans are transmissible and fatal diseases that occur when the normal prion protein (PrPc) mis-folds and accumulates in the brain. The specific function of PrPc within a cell remains unclear, however its presence is essential for prion diseases to occur. This project aims to define how PrPc cleavage affects its biological function(s), and influences susceptibility to prion infection.
Haemolysins And Haemoglobinases As Anti-hookworm Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
To meet its growth and reproductive requirements, hookworms must be able to utilise host haemoglobin located in the red blood cells. To puncture the red blood cell membrane, and break down the exposed haemoglobin into small peptides or single amino acids; the hookworm uses proteases called haemolysins and haemoglobinases. Identifying these proteases and disrupting their function may lead to reduced worm burdens, size and fecundity. Therefore these proteases could be ideal vaccine candidates.
The Role Of Huntingtin Misfolding And Oligomerization In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,329.00
Summary
Mutations in the huntingtin gene cause Huntington's disease by making the gene product aggregate together into non-normal and different sized polymers. However, it is not understood how this process causes cells to die, largely because we don't understand how the abnormal forms accumulate in cells over time. We will examine where in cells the abnormal shapes accumulate and how they cause toxicity. This research will identify critically-needed therapeutic targets against Huntington's disease.
The Influence Of Gamma-secretase Complex Subunits On The Production Of Alzheimer Amyloid Peptides
Funder
National Health and Medical Research Council
Funding Amount
$641,540.00
Summary
Alzheimer's disease is a devastating illness of the aged population and represents a major socio-economic problem in Australia. There is no cure or effective treatment for the illness. A toxic protein fragment known as Abeta amyloid accumulates in the brain of the diseased patients. This is produced by an enzyme called gamma-secretase. This project will investigate different forms of gamma-secretase to gain information useful for developing Alzheimer-specific drugs with little side-effects.
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
Structure-function Inter-relationships Of Small Heat-shock Chaperone Proteins
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jak ....In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases. Nature has evolved cellular mechanisms to minimise protein misfolding, aggregation and precipitation which principally utilise a diverse group of controlling or regulatory proteins called molecular chaperones. Amongst the most important of these are the small heat-shock proteins (sHsps) which are found in all organisms. sHsps function by interacting in a very efficient manner with destabilised proteins to prevent their precipitation. Little is known, however, about the structure of sHsps nor the mechanism by which they perform their chaperone action. This proposal will address these fundamental aspects via the use of a variety of spectroscopic techniques, principally nuclear magnetic resonance (NMR) spectroscopy.Read moreRead less
Structure And Function Of The AMPK Glycogen-binding Domain
Funder
National Health and Medical Research Council
Funding Amount
$538,764.00
Summary
The AMP-activated protein kinase (AMPK) is an enzyme responsible for coordinating metabolism in response to energy supply (diet) and energy demand (exercise). Research into this kinase can increase our understanding of how diet and exercise are so important for maintaining health. The kinase acts either by sensing when cellular energy levels become too low for normal functioning or when the body tells it by sending a chemical messenger (hormone) that overall energy levels are low. This results i ....The AMP-activated protein kinase (AMPK) is an enzyme responsible for coordinating metabolism in response to energy supply (diet) and energy demand (exercise). Research into this kinase can increase our understanding of how diet and exercise are so important for maintaining health. The kinase acts either by sensing when cellular energy levels become too low for normal functioning or when the body tells it by sending a chemical messenger (hormone) that overall energy levels are low. This results in activation of energy-producing pathways and inhibition of energy-consuming pathways, allowing cells to match supply with demand to ensure their survival. The AMPK comprises of three proteins that together form a functional enzyme. I have previously found that AMPK localizes to a source of cellular energy called glycogen (sugar stores) via one part that I have called the glycogen-binding domain. In this application I aim to obtain a thorough understanding of the molecular basis of how the glycogen-binding domain affects AMPK function in muscle and heart following exercise. In addition this research may lead to the identification of new molecules, similar to glycogen, that are important for AMPK regulation and may lead to the development of a new class of drugs for Type 2 Diabetes. Research into AMPK promises to dramatically increase our knowledge of how to reduce the risk of cardiovascular and neurodegenerative diseases, diabetes and obesity and provide an understanding of the reasons these diseases develop.Read moreRead less