A Novel Non-invasive Diagnostic Imaging Technique Of Metastatic Cancer Using Plasminogen Activator Inhibitor Type 2.
Funder
National Health and Medical Research Council
Funding Amount
$187,750.00
Summary
This project aims to develop a non-invasive tumour diagnostic imaging agent based on a non-toxic protein (PAI2) that we know specifically identifies a critical marker of malignancy. PAI2 will be labelled with commonly used imaging radioisotopes. This novel imaging technique has important potential clinical uses including, determination of the most appropriate treatment for individual patients, assessing the success of such treatments, and a novel non-invasive prognostic indicator of malignancy.
After infection with viruses, parasites and bacteria the protein SerpinB2 becomes very abundant in macrophages, which are white blood cells involved in inflammation. Unfortunately, what this protein is doing is very unclear. We have found that macrophage SerpinB2 dampens the responses of other immune cells. This grant aims to determine how this is achieved and thereby help resolve the role of this protein in a number of diseases such as cancer, lupus, asthma and pre-eclampsia.
Proteases, Their Inhibitors And Receptors In Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,843,388.00
Summary
Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin super ....Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin superfamily of protease inhibitors and their protease partners. He is currently the scientific director of the Victorian Bioinformatics Consortium and an NHMRC Senior Research Fellow. Dr Bird is an NHMRC Senior Research Fellow who discovered the intracellular branch of the serpin superfamily and formulated the hypothesis that describes their function. A-Prof Mackie is a world expert in the field of musculoskeletal biology and pathology. Dr Bottomley is a Senior Logan Fellow and RD Wright Fellow whose research focuses upon how proteins misfold and lead to disease. Dr Pike is an enzymologist whose research area encompasses a wide range of bacterial and mammalian proteases involved in the pathology of human disease. Each individual in this team brings different skills which makes this a very important and powerful collaboration. The research is extensive and involves protein folding, enzyme kinetics, molecular modelling, structural biology, bioinformatics, cell biology and pathology, enzyme kinetics and drug design. Collectively the CI’s have a total of 154 papers since 1998, of which a third include two or more of the CI’s as co-authors. Currently the team holds over >$5 million in grant funding. The team is augmented by four P.I.s: Dr Buckle is a talented structural biologist; Dr Scott is a molecular cell biologist who holds an NHMRC CJ Martin Fellow; Dr Garcia de la Banda is a computer scientist based at Monash and Dr Grigoryev is a world expert in chromatin condensation based at Penn State University (USA).Read moreRead less
Regulation Of Leukocyte Lifespan By Granzyme B And PI-9
Funder
National Health and Medical Research Council
Funding Amount
$816,673.00
Summary
To fight infection or cancer the body produces specialized cells called cytotoxic lymphocytes (CLs) which target and eradicate abnormal cells. The number of CLs increases dramatically during infection, and decreases following infection. How this population decrease is controlled is not fully understood, but we propose that a protein used by the CL to kill targets also triggers suicide of the CL after it has destroyed a certain number of targets. How this is achieved is the focus of this project.
Scabies is caused by microscopic mites burrowing through the skin, causing intense itching and providing prime breeding sites for bacteria. The resulting skin sores are very common among Aboriginal children in Australia leading to extreme levels of rheumatic fever-heart disease and renal failure in Indigenous communities. We have discovered mite products termed Serpins which interfere with the patients defence against the mites and the bacteria and aim to develop therapeutics.