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.
Self-destructing CRISPR-constructs For Targeted Genome Editing In The Retina.
Funder
National Health and Medical Research Council
Funding Amount
$679,926.00
Summary
Despite the identification of specific mutations causing many inherited retinal dystrophies, all of these conditions are currently untreatable. We have established gene-editing techniques and have developed a novel mouse model, which will serve as a robust platform for testing different techniques of gene editing in the retina. No other group in the world is known to be using this platform for gene editing and our work will expedite the clinical translation of this technology.
The Use Of Gene-Silencing Nanodrugs To Inhibit Lung Cancer Growth
Funder
National Health and Medical Research Council
Funding Amount
$452,950.00
Summary
Lung cancer accounts for the most cancer deaths worldwide. This research proposal will use state-of-the-art nanomedicines designed to penetrate lung tumours and suppress a gene which drives cancer growth and resistance to chemotherapy drugs. Our results could underpin new approaches that revolutionise more effective and less toxic treatments for a highly lethal malignancy.
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.
Epilepsy is a devastating disease with many patients poorly treated. We have identified a novel ion channel target in the brain that reduces seizure susceptibility. The aim of this proposal is to fully explore this target in a number of epilepsy mouse models using both pharmacology and molecular techniques.
Chromatin Regulation Of Neural Stem Cell Multipotency
Funder
National Health and Medical Research Council
Funding Amount
$756,142.00
Summary
The genetic material is packaged in the cell nucleus with histone proteins. Chemical modifications of histones determine if a particular area of the genome is active or repressed. We are investigating a family of histone modifying proteins, the MYST proteins. Mutations in these proteins cause intellectual disability and cancer. In this project we examine the role of MYST2 in brain stem cells. Knowledge gained may become the basis for the development of drugs to treat neurodegenerative disease.
Epigenetic Regulation Of Monoallelic Gene Expression During Development.
Funder
National Health and Medical Research Council
Funding Amount
$655,035.00
Summary
Upon completion of the human genome sequence focus has shifted to understanding the epigenetic mechanisms that help interpret the encoded information to allow the cell growth and differentiation essential for an organism during development. These mechanisms are disrupted in diseases like cancer, where gene expression is disrupted to favour disease progression. This project will study the genes and epigenetic mechanisms that determine how gene expression patterns are established and maintained.
Understanding The Regulation Of Craniofacial Development Through Control Of Chromatin And Gene Transcription
Funder
National Health and Medical Research Council
Funding Amount
$616,372.00
Summary
Cleft lip and palate are among the most common birth defects. Key genes regulating palate development are sensitive to disturbance by environmental factors. We use this system to comprehensively determine a molecular pathway that is at the interface between the environment and gene transcription. Knowledge gained in the project will draw a framework for our understanding of how environmental insults affect chromatin configuration and gene expression and will inform the basis of measures to preve ....Cleft lip and palate are among the most common birth defects. Key genes regulating palate development are sensitive to disturbance by environmental factors. We use this system to comprehensively determine a molecular pathway that is at the interface between the environment and gene transcription. Knowledge gained in the project will draw a framework for our understanding of how environmental insults affect chromatin configuration and gene expression and will inform the basis of measures to prevent birth defects.Read moreRead less
Identifying Brain Pathways Responsible For Stress Induced Obesity
Funder
National Health and Medical Research Council
Funding Amount
$895,663.00
Summary
Obesity-associated diseases are leading causes of death and are expected to increase as the obesity epidemic worsens. New evidence also shows that stress, an ever-increasing factor of life, can when combined with high caloric food lead and accelerate the development of obesity. The results from this study will help to identify new agents that may help reduce body weight and fat mass particular under conditions of increased stress.
Novel Therapeutic Approaches To Ovarian Clear Cell Cancer
Funder
National Health and Medical Research Council
Funding Amount
$500,920.00
Summary
Our study aims to develop novel therapies for clear cell ovarian cancer, a disease that is generally resistant to conventional therapies. We have found unexpected parallels between kidney cancer and ovarian clear cell cancer, and this has been used to better treat patients. This study investigates the underlying molecular changes the control ovarian clear cell cancer growth.