Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Discovery and characterisation of novel spider-venom peptides targeting the human sodium ion channel Nav1.7. Drugs that selectively block the human sodium ion channel Nav1.7 are likely to be powerful analgesics for treating a wide variety of pain conditions. However, it has proved difficult to obtain selective blockers of this channel. The aim of this project is to determine whether spider-venoms might provide a source of highly selective Nav1.7 blockers.
Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins th ....Unravelling the molecular diversity and evolution of centipede venoms. The project intends to improve understanding of venom evolution in centipedes. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range of animals studied, with many groups of venomous animals overlooked. One such group is centipedes, whose venoms contain diverse toxins that differ between taxa. This project aims to provide an insight into centipede venom evolution, and how it might be constrained by venom-gland morphology. This study seeks to contribute to our understanding of protein evolution and direct biodiscovery efforts around centipede venom.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC is ....Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC isoforms with desirable properties. Ultimately, the project aims to identify isoforms that improve plant fitness under stress conditions. Optimising PEPC activity will provide next generation solutions to improve water balance and carbon assimilation to keep C4 crops productive under future climates.Read moreRead less
Exploring the catalytic role of the Rubisco small subunit: a new target for improving carbon dioxide-fixation in plants. This project uses new biotechnological tools to improve the performance of the photosynthetic protein Rubisco, the primary carbon dioxide-fixing enzyme in plants. By supercharging photosynthesis, this research will help to boost yield and reduce water and nitrogen use in crops.
Rubisco for all climates: unlocking the enzyme's structure-function relations for more efficient photosynthesis. This projects biotechnological research will identify structural features in the carbon dioxide (CO2)-capturing enzyme from plants that improve its performance, particularly at warmer temperatures. This knowledge is vital for predicting the influence of climate change on crop productivity and paving the way for supercharging photosynthesis to boost crop performance.
Novel Insights Into The Mechanisms Of How Viruses Cause Arthritis-arthralgia
Funder
National Health and Medical Research Council
Funding Amount
$626,459.00
Summary
Many viruses are known to cause arthritis (e.g. HIV, hepatitis viruses, mosquito borne viruses). Symptoms of viral arthritis include joint pain, stiffness, and swelling. The mechanism of disease is poorly understood. We have developed a novel animal model of disease by which to study arthritic disease caused by viral infections. This model provides an excellent opportunity to explore the mechanisms of rheumatic disease in a complete functioning animal and to explore new treatment regimes.