Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.
ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100068
Funder
Australian Research Council
Funding Amount
$240,000.00
Summary
Mass spectrometry platform for high throughput genotyping, epigenetic analysis and validation of genome wide sequencing studies. This facility will provide a platform for Australian researchers to quantitatively measure genetic information in a rapid, accurate and cost-efficient manner. This technology will enhance Australia's ability to perform basic research into the genetic and epigenetic mechanisms of cellular function.
How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is funda ....How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is fundamental to the development of all living organisms, this work could have wide implications for understanding all biology – from microbes, insects and plants to humans.Read moreRead less
Mediator: a new concept for controlled gene expression in plant biotechnology. The Mediator protein complex is a new control point for the activation of all genes in higher organisms and the purpose of this project is to understand how three Mediator subunits regulate disease resistance in plants. The outcomes provide a new concept to direct natural gene expression towards robust crop plants able to cope with climatic variations.
Molecular Characterisation Of Early Precursor Lesions Of A Novel Ñserrated Pathwayî Of Colorectal Cancer Using Gene Expression And Proteomics.
Funder
National Health and Medical Research Council
Funding Amount
$318,338.00
Summary
In Australia, CRC is the second highest cause of all cancer-related deaths. If detected early, CRC has a high success rate of cure, but a percentage of precursor lesions escape detection and show aggressive clinical behaviour to progress to CRC. These are difficult to diagnosis with existing technologies. We aim to understand the biology behind sessile serrated adenoma pathways and hence enhance early detection, diagnosis and treatments strategies.
Testing co-evolutionary processes driving venom diversity in tiger snakes. Testing co-evolutionary processes driving venom diversity in tiger snakes. This project aims to examine the geographic variation amongst tiger snakes in anatomy, ecology, and life history traits, and the relationship of these factors to venom toxins and production; and to evaluate the true pharmacological potential of tiger snake venom. This project will investigate the role of venom adaptation in long-term animal evoluti ....Testing co-evolutionary processes driving venom diversity in tiger snakes. Testing co-evolutionary processes driving venom diversity in tiger snakes. This project aims to examine the geographic variation amongst tiger snakes in anatomy, ecology, and life history traits, and the relationship of these factors to venom toxins and production; and to evaluate the true pharmacological potential of tiger snake venom. This project will investigate the role of venom adaptation in long-term animal evolution, by identifying rare venom transcripts involved in providing evolutionary potential for adaptation to environmental change. This is essential as continuing climatic and human-induced alteration of our environment affects southern Australia where many people live, work and interact with native wildlife. Anticipated outcomes are maximizing venom harvests and enhanced snakebite treatment capacity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0667981
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Kangaroo Genome Resource Management Facility. Increasingly, large Australian multicentre research programs in biological and medical sciences have a genomics component that involves integration of biological information with sequencing data. The success of these research programs depends on rapid internet access to the research information by all participating scientists. The universal design of the proposed information management system means that it can be easily adapted to support a broad ran ....Kangaroo Genome Resource Management Facility. Increasingly, large Australian multicentre research programs in biological and medical sciences have a genomics component that involves integration of biological information with sequencing data. The success of these research programs depends on rapid internet access to the research information by all participating scientists. The universal design of the proposed information management system means that it can be easily adapted to support a broad range of research programs. The development of this software program therefore has the potential to benefit research scientists, academics and students in many related fields, as well as the broader community, through enhancing research outcomes.Read moreRead less