Molecular Genetics And Evolution Of Antibiotic Resistant Staphylococci
Funder
National Health and Medical Research Council
Funding Amount
$437,545.00
Summary
Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Hospital-acquired infections caused by Golden Staph are a major problem in Australia and globally. The problem is largely due to the pre ....Potentially life-threatening infections caused by Staphylococcus aureus bacteria, commonly known as Golden Staph, often arise as complications in patients within hospitals. These infections compromise the health of the patient and jeopardise their recovery from the condition for which they were initially admitted, which significantly increases healthcare costs. Hospital-acquired infections caused by Golden Staph are a major problem in Australia and globally. The problem is largely due to the presence in hospitals of strains that have become resistant to most clinically-useful antibiotics and are therefore very difficult to eradicate. This research project will reveal detailed information about strains of Golden Staph that are currently prevalent in hospitals in Australia, USA, Europe, and South East Asia. It will also provide important insights into the mechanisms that enable this organism to become resistant so readily, and identify factors that promote the development of resistant strains. The results of this research project will lead to improved methods for the characterisation of clinical strains and the monitoring of antibiotic resistance. The findings will also be of relevance to other types of antibiotic resistant bacteria. Most importantly, the application of knowledge arising from these studies has potential to minimise the emergence of strains that are even more resistant, thereby extending the effectiveness of existing and future antibiotics. The design and implementation of strategies to limit the proliferation of resistant bacteria are essential if we are to avoid a scenario similar to that prior to the introduction of antibiotics, when serious infectious diseases were often untreatable.Read moreRead less
Characterization Of Neutralizing Antibody Responses In HCV Infected Individuals.
Funder
National Health and Medical Research Council
Funding Amount
$478,076.00
Summary
Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attri ....Hepatitis C virus is a major human pathogen infecting 200 million people world-wide. Currently, there is no vaccine to prevent infection and treatment regimes are only partially effective. IInitial HCV infection is frequently asymptomatic and 30% of people spontaneously clear the virus. The remaining 70% of people develop a life-long chronic infection that causes progressive liver disease, cirrhosis and in some cases liver cancer. The reason why some people are able to clear virus has been attributed to the development of a strong cellular immune response and antibody is belived to play a monir role in achieving viral clearance. However, measurememnt of antibody responses in HCV infected pateints is routinely performed using conventional diagnostic tests that do not measure antibody that can help neutralize and clear virus. We have developed an assay that accurately measures the level of NAb in patient sera. We have found that chronically infected patients have broadly reactive neutralizing antibodies but that patients who clear virus, naturally or through treatment do not have broadly reactive neutralizing antibodies. Possibly explaining this phenomenon is that early during infection, antibody is frequently specific only to the infecting virus therefore to detect neutralizing antibodies, homologous viral sequences must be examined. In addition, we have found evidence that HCV can evade neutralzing antibodies through masking of sites to which antibodies bind. We propose to explore whether acutely infected patients develop NAb to autologous viral sequences, and how do these viral sequences and the antibody titre change throughout the course of infection and treatment. We also plan to determine the mechanism of neutralization resistance through the use of mutagenesis of resistant HCV glycoproteins. These studies are aimed at gaining a thorough understanding of the true role of antibody in HCV infection and its influence on viral evolution.Read moreRead less
Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.
Treatment Of Genetic Liver Disease By Homologous Recombination In Vivo, Coupled With A Pharmoco-genetic Strategy For Selective Expansion Of Genetically Repaired Hepatocytes
Funder
National Health and Medical Research Council
Funding Amount
$920,836.00
Summary
This project seeks to exploit recent advancements in our ability to precisely “edit” and correct mutations underlying human genetic diseases. To improve therapeutic efficiencies of the system, we will deliver the technology using highly efficient virus-based systems and apply a novel post-repair selection process to preferentially repopulate the liver with gene-repaired cells. Demonstration of the strategy in a humanised mouse model will provide important preclinical data for human applications.
Understanding The Genetic Basis Of Breast Cancer: Translation To Primary And Secondary Prevention
Funder
National Health and Medical Research Council
Funding Amount
$2,731,372.00
Summary
We have identified >200 regions of the genome that contain variants that increase breast cancer risk. I will now focus on the main challenges i.e. to a) find the remaining genetic risk factors that will collectively explain all of the genetic risk, b) understand how these work, in particular which genes they influence and c) apply this knowledge to find and develop new drugs. Importantly, such drugs could be used not only to treat breast cancer, but also to prevent it in high-risk women.