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
Prevalence report by the Australian Advisory Board on Autism Spectrum Disorders (ASD) estimated that 1 child in every 160 children in the 6-12 year-old age group is affected by ASD. There is no cure for ASD and the causes are not understood. We propose that sex hormones may play a role in the development of these disorders. We will test this hypothesis using knockout and transgenic mouse models which have social interaction deficits and brain structure reminiscent of these disorders.
The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the e ....The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the establishment of interdisciplinary collaborations and provision of world-class training for staff and students in the field of reproductive biology. This project should provide significant benefits, such as improved chemical management in livestock production and the development of marsupial conservation action plans.Read moreRead less
Development of Novel Pesticidal Agents. We have discovered a family of naturally occurring plant proteins called the cyclotides that have potent insecticidal activity against Helicoverpa species, one of the major pests on cotton and corn in Australia and world wide. Preliminary evidence has shown that they also have activity against major pests to livestock in Australia, including sheep blowflies. To develop these proteins as potential pesticidal agents it is necessary to understand the struct ....Development of Novel Pesticidal Agents. We have discovered a family of naturally occurring plant proteins called the cyclotides that have potent insecticidal activity against Helicoverpa species, one of the major pests on cotton and corn in Australia and world wide. Preliminary evidence has shown that they also have activity against major pests to livestock in Australia, including sheep blowflies. To develop these proteins as potential pesticidal agents it is necessary to understand the structural basis for their activity. We will do this by chemically synthesising peptides with selected residues mutated to determine their effects on activity.Read moreRead less
Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology c ....Physiology of oxygen transport in the mammalian kidney. This project aims to improve understanding of oxygen regulation in renal tissue and knowledge of the physiology of the kidney. The mammalian kidney receives more oxygen than it uses or needs, and yet renal tissue is commonly found to be hypoxic. This project proposes that oxygen transport to the renal tissue is limited by blood vessel surface area. The project expects to generate anatomical data currently missing from the renal physiology community, and potentially change the accepted story of oxygen homeostasis in the kidney. This will provide significant benefits, such as the provision of the foundational physiological science behind a determinant of kidney health and its flow-on impact to quality of life.Read moreRead less
Cellular and network basis of information processing in the mammalian visual system. The project aims to discover the strategies by which cells in the brain interact with each other to code the sensory input efficiently. It is expected that simultaneous recording of the activity of many neurones from the visual cortex of anaesthetised cats during visual stimulation will reveal how the biophysics of synaptic integration combined with excitatory and inhibitory inputs from different sources sculpt ....Cellular and network basis of information processing in the mammalian visual system. The project aims to discover the strategies by which cells in the brain interact with each other to code the sensory input efficiently. It is expected that simultaneous recording of the activity of many neurones from the visual cortex of anaesthetised cats during visual stimulation will reveal how the biophysics of synaptic integration combined with excitatory and inhibitory inputs from different sources sculpts the output of individual neurones. The experiments will be extended to the study of possible interactions between different areas of the brain and the study of mechanisms by which the cortical network and higher cognitive factors such as attention and memory might influence the coding of sensory information in awake animals.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC230100016
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Training Centre in Predictive Breeding for Agricultural Futures. This Centre aims to develop the advanced capacity needed to secure Australia’s food and fibre production and export value into the future. Leveraging immense industry support, the Centre expects to develop and integrate cutting-edge plant and animal breeding technologies and deliver world-class training that addresses critical demand for highly skilled industry leaders. Expected outcomes include a future-ready predictive breedi ....ARC Training Centre in Predictive Breeding for Agricultural Futures. This Centre aims to develop the advanced capacity needed to secure Australia’s food and fibre production and export value into the future. Leveraging immense industry support, the Centre expects to develop and integrate cutting-edge plant and animal breeding technologies and deliver world-class training that addresses critical demand for highly skilled industry leaders. Expected outcomes include a future-ready predictive breeding industry able to transform data into optimised decisions, and the human capacity to drive it. This should provide significant benefits to enhance the sustainability and profitability of all major Australian agriculture sectors, including livestock, grains, horticulture, cotton, wine, dairy, forestry and fisheries.Read moreRead less
Environmental contamination and pig disease: an Australian microbe evolves. The Australian pig industry produces pork commodities from over 4.75 million pigs per year. Infectious diseases in industrial-scale piggeries can have a devastating effect on pork production, particularly on feed conversion efficiency and growth rates, and can pose downstream environmental contamination and food safety risks. This project aims to assess a current infectious disease problem in pigs by studying a microbe t ....Environmental contamination and pig disease: an Australian microbe evolves. The Australian pig industry produces pork commodities from over 4.75 million pigs per year. Infectious diseases in industrial-scale piggeries can have a devastating effect on pork production, particularly on feed conversion efficiency and growth rates, and can pose downstream environmental contamination and food safety risks. This project aims to assess a current infectious disease problem in pigs by studying a microbe that appears to have uniquely evolved in Australia. These results could inform the rational design of monitoring, prevention and treatment strategies to minimise infection outbreaks in Australian pigs and may result in production benefits to the pork industry, reduced environmental microbial contamination and safer food.Read moreRead less
Old brains, new data - early evolution of structural complexity in the vertebrate head. Of the all the complex structures biology has provided, the evolution of the vertebrate brain and its sensory organs is perhaps the most enigmatic. The fossil record occasionally provides a chance to trace this evolution, but only with the use of novel X-ray scanning techniques can these secrets be detailed in three dimensions. Exploiting the exceptional fossil record from Australia and China, this team will ....Old brains, new data - early evolution of structural complexity in the vertebrate head. Of the all the complex structures biology has provided, the evolution of the vertebrate brain and its sensory organs is perhaps the most enigmatic. The fossil record occasionally provides a chance to trace this evolution, but only with the use of novel X-ray scanning techniques can these secrets be detailed in three dimensions. Exploiting the exceptional fossil record from Australia and China, this team will for the first time collect a vast comparative data base which will yield clues on the early evolution of the ear, eye and brain. Read moreRead less
Nucleolus targeting by negative strand RNA viruses. Negative strand viruses (NSVs) include diverse animal pathogens that represent significant threats to Australian livestock industries and access to export markets. The project aims to investigate the interface formed by NSVs with cellular nucleoli in order to determine roles in viral manipulation of cell biology during infection. This project hopes to address a major gap in knowledge in virology regarding the fundamental biology of NSVs, and is ....Nucleolus targeting by negative strand RNA viruses. Negative strand viruses (NSVs) include diverse animal pathogens that represent significant threats to Australian livestock industries and access to export markets. The project aims to investigate the interface formed by NSVs with cellular nucleoli in order to determine roles in viral manipulation of cell biology during infection. This project hopes to address a major gap in knowledge in virology regarding the fundamental biology of NSVs, and is expected to redefine our understanding of the virus-host interactions formed by these important pathogens. By determining the mechanisms of NSV-nucleolus interaction, the project plans to also provide important information for the development of new vaccines/therapeutics for livestock to combat NSVs that target nucleoli.Read moreRead less