Development And Biological Evaluation Of Cytokine Macrophage-migration Inhibitor (MIF) Non-Steroidal Antagonists
Funder
National Health and Medical Research Council
Funding Amount
$85,000.00
Summary
The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhi ....The cytokine macrophage-migration inhibitory factor (MIF) has a broad range of pro-inflammatory effects in the innate and adaptive immune system. CIA’s lab has demonstrated the potential importance of MIF in the pathology of chronic inflammation via studies in models of rheumatoid arthritis (RA). Similarly to other chronic inflammatory diseases, MIF is overexpressed in human RA, and induces activation of key pathological processes in RA cells. Moreover, antagonism of MIF with mAb profoundly inhibits models of RA and other inflammatory diseases, confirming MIF as a therapeutic target in human inflammatory disease. The X-ray crystal structure of MIF has been published and the putative active site fully characterised. We have deduced structural features of MIF that reveal aspects of the structural complementarity of host-guest affinity. This information has been used in the synthesis of new compounds to antagonise MIF. We have designed, synthesised and tested several classes of compounds, which have shown activity from milli to nano-molar levels in novel in-house in vitro bioassays.Read moreRead less
Characterisation Of A Novel Direct Electrochemical Chip As A Biosensor And Tool For Studying Redox-sensitive Proteins
Funder
National Health and Medical Research Council
Funding Amount
$144,500.00
Summary
Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advanc ....Biosensors use biomolecules to detect a chemical event. They are becoming important for the rapid and reliable measurement of the concentrations of molecules in fluids. In human medicine they will be of great use to general practitioners and patients for instantaneous read outs of concentrations of many different biological molecules. How well a biosensor responds depends on the method in which the biomolecule is immobilised to a surface and the signal detected. We have made a significant advance in biosensing capabilities using a recombinant protein (thioredoxin) and demonstrated the improvement that is possible by (i) immobilising the protein in a highly oriented way and (ii) using a sensitive electrical signal to monitor the response. Here we will undertake more comprehensive testing by extending the number of proteins to include the 4 major classes of redox-sensitive biomolecules (proteins) in the body. This will enable us to establish the broad application of our methods and substantially improve our ability to commercialize our discoveries.Read moreRead less
Toxicological And Pre-clinical Assessment Of The Anti-cancer Compound Bp4eT
Funder
National Health and Medical Research Council
Funding Amount
$198,900.00
Summary
Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Development Grant, we will perform toxicological studies to enable clinical trials of our most promising novel iron chelator to commence.
Proof Of Concept Studies On A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$199,700.00
Summary
The rise of drug-resistant superbugs is a major healthcare concern in hospitals across the world. New antibiotics are needed to combat infections caused by bacteria that are resistant to current drugs. One collaborative team of researchers is addressing the issue. They have discovered a new compound effective against Staphylococcus aureus, the cause of Golden Staph. Using a combination of scientific disciplines the team are now developing this compound into a new antibiotic.
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.
Studies Of Metabolites Of Synthetic Flavonols For The Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$207,440.00
Summary
Cardiovascular disease, including heart attack and stroke, is the leading killer of Australians. A promising new drug, NP202, can reduce the amount of tissue damaged from a heart attack; however, its mechanism of action remains obscure. NP202 is metabolized to a range of compounds, one of which is partly responsible for its beneficial effects. In this project we will identify other metabolites of NP202 and characterize their biological activity to gain insight into its mechanism of action.
Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models ....Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models. We now propose to refine this technique in animals in preparation for human clinical trials.Read moreRead less
The DietAdvice Website A New Innovation For Dietitians In Clinical Practice.
Funder
National Health and Medical Research Council
Funding Amount
$140,975.00
Summary
Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food int ....Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food intakes. The food information is sent to a dietitian who develops individualised dietary advice for them. A pilot study of the website has already found it to be feasible in the primary healthcare setting. Tested for 12 months the website was used by 224 patients from GP practices in the Illawarra region of NSW. Approximately 73% of patients were overweight and patients with a high BMI were 1.88 times more likely to use the website in the comfort of their home. Further research about the website however was needed. The research to follow on from the pilot study will aim to refine the DietAdvice website, leading towards its commercialisation for dietitians in clinical practice. The research will be broken into 3 phases. Phase 1 will involve a usability test of the website, assessing the underlying algorithms and testing it with dietitians in private practice. Phase 2 will see volunteers using the website on multiple occasions after being given pre-weighed amounts of food to eat. This will determine how reliable and accurate the information is; and phase 3 will evaluate whether the website is cost effective and if it increases accessibility of health services especially in rural areas. By confirming these attributes there will be a sound basis to commercialise the product.Read moreRead less
Application Of Follistatin To The Resolution Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$330,990.00
Summary
Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing li ....Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing liver cancer, for which current treatments have limited success. We have been studying two proteins, activin and follistatin, both of which are made in the liver. We are interested in activin because it is one of the body's mechanisms to control cell growth, and also seems to stimulate the development of scar tissue. Follistatin is the natural inhibitory substance for activin. It blocks the effects of activin and helps promote cell growth in the liver. We believe that follistatin may also be useful in controlling liver scarring. This process will be studied in animal models of cirrhosis, in the hope that follistatin treatment will reduce the level of liver damage. If successful, this would be important information that would enable us to design treatments applicable to human sufferers of these liver diseases. In another part of the project, we will assess whether activin and follistatin might be useful markers of liver disease. Most patients require a liver biopsy to assess the amount of liver damage, and a simple blood test would be a far easier, less traumatic and cheaper alternative.Read moreRead less