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
A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conduct ....A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conductance properties of the channel. Accurately
determining these relationships provides a pathway to developing cures
for many neurological, cardiac, and muscular diseases.
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New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-r ....New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-resilient root systems. Importantly, we have discovered specific molecules that either promote or inhibit blood vessel formation. A better understanding of how these molecules work could lead to novel treatments for cancer or cardiovascular disease.Read moreRead less
Elucidating the interactions between drought tolerance and photoprotection in plants. The 2002-03 drought cost Australia in the order of $10Billion and 70,000 jobs. Associated with reduced rainfall is increased sunlight irradiance, which exacerbates the reduction in crop yield due to the combined damage of a water deficit and oxidative damage caused by the excess light. Plants have networks of responses to minimise damage due to drought and excess light. We have identified a novel class of genes ....Elucidating the interactions between drought tolerance and photoprotection in plants. The 2002-03 drought cost Australia in the order of $10Billion and 70,000 jobs. Associated with reduced rainfall is increased sunlight irradiance, which exacerbates the reduction in crop yield due to the combined damage of a water deficit and oxidative damage caused by the excess light. Plants have networks of responses to minimise damage due to drought and excess light. We have identified a novel class of genes that optimise or alter different aspects of these networks and we wish to define the nature of that optimisation to determine how it could be transfered to crop plants.Read moreRead less
Chloroplast pigments as developmental signals. This project will define roles of chloroplast pigments in cellular signaling, plant growth and development. Effective communication between the chloroplast and the nucleus is essential for maintaining viability and productivity of the cell. Similarly, long-distance signaling is required for coordinated growth and development and we hypothesise that pigments also have importance in this role. Our proposal brings together the multidisciplinary skills ....Chloroplast pigments as developmental signals. This project will define roles of chloroplast pigments in cellular signaling, plant growth and development. Effective communication between the chloroplast and the nucleus is essential for maintaining viability and productivity of the cell. Similarly, long-distance signaling is required for coordinated growth and development and we hypothesise that pigments also have importance in this role. Our proposal brings together the multidisciplinary skills and resources of six investigators to define how certain carotenoids and chlorophyll precursors regulate gene expression and to determine the identity of what is most likely a carotenoid derivative with hormonal properties that controls lateral branch growth.Read moreRead less
Pathogen recognition and plant-defence activation by a novel Fusarium wilt-resistance protein from tomato. The devastating effects of Fusarium wilt disease of tomato is a threat to one of Australia's most economically important horticultural crops. Resistant tomato varieties offer the most effective means of control but the fundamental mechanisms underlying this resistance are yet to be understood. This research will increase our understanding of resistance to Fusarium wilt disease. The knowledg ....Pathogen recognition and plant-defence activation by a novel Fusarium wilt-resistance protein from tomato. The devastating effects of Fusarium wilt disease of tomato is a threat to one of Australia's most economically important horticultural crops. Resistant tomato varieties offer the most effective means of control but the fundamental mechanisms underlying this resistance are yet to be understood. This research will increase our understanding of resistance to Fusarium wilt disease. The knowledge gained will assist in the development of new robust, sustainable approaches to disease control, as well as the development of pre-emptive strategies to avert major outbreaks, which will ensure reliable productivity and minimal economic losses into the future.Read moreRead less
Translocation of secreted effector proteins from fungal pathogens into host plant cells. Every year, fungal diseases of plants cause huge losses in agricultural productivity and extensive environmental damage in Australia. Disease control in major crops, like wheat, currently relies heavily on breeding for disease resistance. However, fungal pathogens continually adapt to overcome plant defences, necessitating identification of new sources of resistance. The research in this project will eluc ....Translocation of secreted effector proteins from fungal pathogens into host plant cells. Every year, fungal diseases of plants cause huge losses in agricultural productivity and extensive environmental damage in Australia. Disease control in major crops, like wheat, currently relies heavily on breeding for disease resistance. However, fungal pathogens continually adapt to overcome plant defences, necessitating identification of new sources of resistance. The research in this project will elucidate the molecular basis of a new aspect of the establishment of plant infection by fungi, and in so doing will provide new avenues for the development of novel disease resistance strategies, with relevance in particular to devastating cereal diseases like wheat rust.Read moreRead less
Role of fungal secreted proteins as plant disease effectors. Many crop diseases are economically significant threats to agricultural productivity in Australia, with rust fungi in particular being a major problem for cereal grain production. Current methods of rust disease control are based on breeding for resistance but continued adaption by rust fungi to overcome plant defences means there is an urgent need for new methods of crop protection. This project will investigate molecular processes ....Role of fungal secreted proteins as plant disease effectors. Many crop diseases are economically significant threats to agricultural productivity in Australia, with rust fungi in particular being a major problem for cereal grain production. Current methods of rust disease control are based on breeding for resistance but continued adaption by rust fungi to overcome plant defences means there is an urgent need for new methods of crop protection. This project will investigate molecular processes underlying fungal infection of plants, focusing on mechanisms that enable fungi to take over the metabolism of infected cells. The research will provide basic knowledge for development of novel and durable disease resistance strategies.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.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.