Dietary Protein-induced DNA Damage In Colon And Consequences For Colorectal Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$604,797.00
Summary
This research will explore the effects of dietary protein on genetic damage to cells lining the large bowel and risk of developing colorectal cancer. We will determine the degree and type of DNA damage resulting from increased protein, the cellular response to this DNA damage, whether it increases risk for developing bowel cancer and whether it can be minimised by other foods in both an animal model and humans.
Novel Mechanisms Of Genotoxicity: Bioactivation Of Carboxylic Acid Drugs By UDP-glucuronosyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
Before any new pharmaceutical products are approved for clinical use, they undergo extensive testing to demonstrate both efficacy and safety. Part of this testing involves ensuring that, within the body, they are not converted to chemically reactive forms able to damage DNA, since DNA damage can lead to cell toxicity or the development of cancer. Our laboratories have recently identified a new mechanism by which the body converts drugs to reactive chemicals called ester glucuronides. We have sho ....Before any new pharmaceutical products are approved for clinical use, they undergo extensive testing to demonstrate both efficacy and safety. Part of this testing involves ensuring that, within the body, they are not converted to chemically reactive forms able to damage DNA, since DNA damage can lead to cell toxicity or the development of cancer. Our laboratories have recently identified a new mechanism by which the body converts drugs to reactive chemicals called ester glucuronides. We have shown that some ester glucuronides can damage DNA. A large number of different drugs have the potential to form ester glucuronides. However, we do not know whether all ester glucuronides cause DNA damage or, if only some do, what properties determine their DNA damaging potential. In addition, most of the current pre-clinical screening of drugs can not detect DNA damage caused by ester glucuronides. We believe this lack of knowledge is of serious concern. Therefore, this project aims to: i) screen a large number of drugs for ester glucuronide-mediated DNA damage; ii) develop some preliminary methods of predicting the DNA damaging potency of these reactive chemicals; and iii) develop a screening test that may be more suitable for detecting DNA damage by ester glucuronides during pre-clinical testing. Such work is essential to ensure the ongoing safety of all pharmaceutical agents.Read moreRead less
Development Of A Sensitive Point Of Care Diagnostic Assay For Troponin I
Funder
National Health and Medical Research Council
Funding Amount
$137,650.00
Summary
This research aims to develop a diagnostic for immediate monitoring of patients presenting with chest pain, with the presumption of heart attack. The novel diagnostic platform will enable the estimation of a key indicator of heart muscle damage to be performed within a ten to fifteen minute window. This will aid speedier diagnosis and propoer triage of patients presenting with chest pain.
Culture-independent Microbiology: Reducing Delays In The Diagnosis Of Severe Infections And Detection Of Antimicrobial Resistance From Days To Hours.
Funder
National Health and Medical Research Council
Funding Amount
$949,589.00
Summary
Serious infections require early effective antibiotic treatment. To provide evidence that an antibiotic will be effective, current tests take 2-5 days and this leads to a reliance on broad spectrum antibiotics, which can cause harm. Our new diagnostic methods, can produce results in 4-6 hours. We will demonstrate the real-world benefit of these methods by assessing samples taken from patients with three high risk infections and compare our test to currently available results.
Novel Genes And Protein In Non-alcoholic Fatty Liver Disease: Potential Basis Of A Serum-based Assessment Of Disease Sta
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infe ....The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infection with the hepatitis C virus. We obtained liver biopsies from patients with NAFLD, 80% of whom had NASH, and determined the expression profile analysis of each subject using 19,200 element microarrays. Our data demonstrates the concordant differential expression of 130 genes, in subjects with NAFLD that were categorizes into 6 major metabolic and regulatory pathways. Many of these genes represented uncharacterised genes. Utilising an extensive bioinformatics approach we have been able to define the genes and their protein product. The use of these proteins as a diagnostic tool for the detection of NAFLD forms the basis of a provisional patent application. However, measurements of protein levels in tissue and sera from patients with NAFLD are needed for the development of a diagnostic method. Such information would also provide significant insight into the pathogenesis of NAFLD. The AIMS are: 1) Production of antibodies against proteins encoded by candidate genes Expression profile of candidate genes 3) Expression of proteins encoded by candidate genes in patients with NAFLDRead moreRead less
Improving Immunoassays For The Diagnosis Of Latent Tuberculosis Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$489,006.00
Summary
WHO highlights the urgent need for new tests for tuberculosis (TB). Diagnosis of latent TB infection (LTBI) is vital in children to prevent them developing active TB. A tuberculin skin test has long been used but is not always accurate. More accurate blood tests (immunoassays) have recently been developed which improve the diagnosis of LTBI in adults. However, we have shown that these assays do not work well in children. We aim to improve the performance of immunoassays for diagnosing LTBI in ch ....WHO highlights the urgent need for new tests for tuberculosis (TB). Diagnosis of latent TB infection (LTBI) is vital in children to prevent them developing active TB. A tuberculin skin test has long been used but is not always accurate. More accurate blood tests (immunoassays) have recently been developed which improve the diagnosis of LTBI in adults. However, we have shown that these assays do not work well in children. We aim to improve the performance of immunoassays for diagnosing LTBI in children.Read moreRead less
Rapid Point Of Care Detection Of Avian Influenza Virus Using Ion-Channel Switch Biosensor
Funder
National Health and Medical Research Council
Funding Amount
$425,400.00
Summary
The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in cl ....The project aims to demonstrate a rapid, Point-of-Care test based on the Ion Channel Switch (ICS_) Biosensor for the detection and identification of Avian Influenza (AI) Virus in respiratory specimens. This proposal combines the extensive scientific skills and experience of the Institute of Medical and Veterinary Science (IMVS), Adelaide with the experience and existing capability of Ambri Ltd, Chatswood Sydney, to adapt an existing ICS_ Biosensor for the detection of avian influenza virus in clinical specimens. The existing ICS_ Biosensor has been shown to have reactivity with inactivated Influenza A (H1N1 and H3N2 _ current, circulating human strains) and with recombinant Nucleoprotein. This unique mix of experience and infrastructure will permit the demonstration a rapid, point-of-care test for Avian Flu within the tight six months schedule.Read moreRead less