Interactions Between Integrative Genomic Islands And Plasmids; Role In The Spread And Loss Of Antibiotic Resistance And Pathogenicity Determinants
Funder
National Health and Medical Research Council
Funding Amount
$776,465.00
Summary
Mobile elements that integrate into bacterial chromosomes at a specific site contribute pathogenicity and antibiotic resistance determinants to their bacterial host but only a few are able to move themselves into new hosts. Some plasmids and some elements can help certain others. In this project, genetic approaches will be used to investigate how plasmids and integrative elements help one another move into a new bacterium or compete with one another to stay in the same cell.
Molecular Basis For Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$872,660.00
Summary
There has been growing concern about the increasing level of antibiotic resistance in bacterial pathogens. We will use a model genetic element to determine the mechanism by which an important class of pathogenic bacteria can acquire new resistance genes by a process known as horizontal gene transfer. The project will significantly enhance our understanding of how major hospital and community acquired pathogenic bacteria can rapidly evolve to become resistant to different antimicrobial agents.
Gene Therapy For Preventing Progressive Sensorineural Hearing Loss And Restoring Hearing
Funder
National Health and Medical Research Council
Funding Amount
$549,848.00
Summary
This proposal aims to study the clinical feasibility and safety of gene therapy in the guinea pig cochlea for preventing progressive hearing loss and restoring hearing. Two cell survival genes (GDNF and BDNF) will be studied for preserving sensory (hair) cells and hearing nerves, while a gene called Atoh1 will be investigated for its ability to regenerate new hair cells and restore hearing after the onset of progressive hearing loss.
Directed Evolution Of AAV Capsid Variants For Enhanced Targeted Genome Editing In The Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$386,012.00
Summary
Liver transplantation is often the only treatment option available for patients with severe liver disease, and is complicated by a shortage of donor organs and the need for life-long drug therapy to prevent rejection. Repair of a patient’s own liver by gene therapy is a promising alternative. This project focuses on developing the technology required to undertake precise correction of genetic spelling errors in diseased liver cells without the need to first remove them from the body.
The Mechanism Of Conjugative Transfer Of Antibiotic Resistance Genes In Gram Positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Antibiotic resistant bacteria pose a serious threat to the health of Australians. We will determine how antibiotic resistance genes spread from one bacterium to another. Using a disease-causing bacterium as model we will determine the mechanism by which this gene transfer process occurs and the structure and function of the key components. The result will be major advances in our understanding of the evolution of the antibiotic resistant bacteria that are major causes of human disease.
Pulmonary hypertension is a disease affecting the blood vessels in the lungs that causes severe shortness of breath and early death. Genetic mutations are known to cause this disease but the precise link between these mutations and the changes in the lungs are poorly understood. If we could understand this process better, we could design better treatments. This project will look at how the cells in the lungs communicate with each other and how this process is disturbed in pulmonary hypertension.
Role Of IS26 In Antibiotic Resistance Gene Recruitment, Dissemination And Expression
Funder
National Health and Medical Research Council
Funding Amount
$457,879.00
Summary
Antibiotic resistance is increasing, compromising the efficacy of front-line antibiotics. Untreatable infections due to bacteria that are resistant to all available antibiotics are being seen more often. To control the spread of resistance, an understanding of how resistance arises and is spread among bacteria is needed. This requires information about how the genetic elements that mobilize them work. This project will study one of the most important of these elements.
Strategies To Achieve Kidney Transplant Tolerance In A Clinically-relevant Model
Funder
National Health and Medical Research Council
Funding Amount
$663,490.00
Summary
The acceptance of kidney transplants without immunosuppression (tolerance) would avoid the side effects of these powerful drugs and improve long-term graft survival. Donor brain death causes inflammation in transplanted kidneys which can block tolerance. In this project, we aim to determine whether expression of a naturally-occurring soluble anti-inflammatory molecule in the liver can prevent this inflammation, allowing tolerance to develop.
Solving Delivery Of Gene Therapy For Control Of Human Immunodeficiency Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$765,439.00
Summary
Antiretroviral therapy free control of Human Immunodeficiency Virus (HIV) infection requires control of the viral reservoir. We have a unique approach, aimed at enforcing HIV latency by targeting highly conserved regions in the viral promoter. These constructs completely silence viral transcription for long periods of time. We intend to develop & assess vectors that are specifically targeted to the reservoir and which can enforce viral latency despite immune activation or viral variation.
Non-invasive Gene Delivery For Expression Of Therapeutic Genes In Oligodendrocytes: A New Strategy To Treat Myelin Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$594,393.00
Summary
White matter diseases are debilitating childhood disorders caused by defects in the insulating myelin sheath normally covering and protecting the nerve fibres from damage. There is currently no effective treatment but the delivery of a genetic medicine to the diseased myelin forming cells in the brain could be curative. This project aims at establishing the safe, efficient and non-invasive delivery of therapeutic genes to myelin forming cells as a gene therapy for white matter disorders.