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
The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integ ....The role of the Ttyh1 protein in cell activation. We have cloned TTYH1, a human homologue of the Drosophila melanogaster tweety gene. The mouse gene has also been identified. The predicted structure of the protein is a membrane protein with 5 transmembrane domains. We have also expressed a GFP-tagged fusion protein in mouse fibroblasts. Confocal microscopy indicates that this protein is likely to be a novel adhesion molecule, with a cellular distribution characteristic of molecules such as integrins. We aim to determine the function of Ttyh1, its interacting intra- and extra-cellular proteins and to assess its candidature as a molecule of importance in cell migration and adhesion.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
Plant immunity to fungal and bacterial pathogens. Since 2003, the Australian wheat crop has been threatened by a continuing stripe rust epidemic, which has required an additional production expense of at least $100 million per annum in fungicides. This Australian National University (ANU) - Commonwealth Scientific and Industrial Research Organisation (CSIRO) joint proposal aims to exploit the next-generation genome sequencing and associated bioinformatic and proteomic methods which are poised to ....Plant immunity to fungal and bacterial pathogens. Since 2003, the Australian wheat crop has been threatened by a continuing stripe rust epidemic, which has required an additional production expense of at least $100 million per annum in fungicides. This Australian National University (ANU) - Commonwealth Scientific and Industrial Research Organisation (CSIRO) joint proposal aims to exploit the next-generation genome sequencing and associated bioinformatic and proteomic methods which are poised to revolutionise biology to investigate the wheat-fungus interaction. We will develop new effective approaches for environmentally benign stripe rust control based on new knowledge about how this fungus causes disease and avoids the wheat's immune surveillance system.Read moreRead less
The Awakening of Faith and New Confucian Philosophy. This project aims to provide a new understanding of how New Confucian philosophy was constructed in modern China. It proposes to debunk the prevailing myth that modern Chinese philosophy owes its identity as a continuation of Confucianism, to the exclusion of the fundamentally ‘foreign’ influence of Buddhism. It is anticipated that this project will substantially advance the knowledge base of Chinese philosophy both in Australia and internatio ....The Awakening of Faith and New Confucian Philosophy. This project aims to provide a new understanding of how New Confucian philosophy was constructed in modern China. It proposes to debunk the prevailing myth that modern Chinese philosophy owes its identity as a continuation of Confucianism, to the exclusion of the fundamentally ‘foreign’ influence of Buddhism. It is anticipated that this project will substantially advance the knowledge base of Chinese philosophy both in Australia and internationally, and will also contribute to a more informed understanding of the philosophical and religious traditions our neighbours use to define national and cultural identity.Read moreRead less
Sisters and Sojourners: Stories of Rural Women in Urban China. A large increase in unofficial rural to urban migration has been one of the most significant aspects of social change in China in the last two decades. This project aims to advance our understanding of this phenomenon through a study of rural Chinese women's experiences of migration to the city, and in particular, the effects of migration upon their sense of identity, worldview and relationships with others. The project will involv ....Sisters and Sojourners: Stories of Rural Women in Urban China. A large increase in unofficial rural to urban migration has been one of the most significant aspects of social change in China in the last two decades. This project aims to advance our understanding of this phenomenon through a study of rural Chinese women's experiences of migration to the city, and in particular, the effects of migration upon their sense of identity, worldview and relationships with others. The project will involve ethnographic fieldwork, centring on the collection and analysis of rural migrant women's life stories. It will result in the publication of a book and three scholarly articles.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100386
Funder
Australian Research Council
Funding Amount
$435,875.00
Summary
Anti-racist neuroethics for epistemic justice in mental health research. Racial/ethnic minorities are underrepresented in brain and mental health (BMH) research, risking inadequate healthcare for the 9.5 million minorities in Australia. With the $73 billion annual cost of BMH disorders to the country, all Australians should equally benefit from BMH research. This project aims to develop recommendations to make BMH research more diverse and inclusive. It will audit representation of minorities in ....Anti-racist neuroethics for epistemic justice in mental health research. Racial/ethnic minorities are underrepresented in brain and mental health (BMH) research, risking inadequate healthcare for the 9.5 million minorities in Australia. With the $73 billion annual cost of BMH disorders to the country, all Australians should equally benefit from BMH research. This project aims to develop recommendations to make BMH research more diverse and inclusive. It will audit representation of minorities in Australian BMH publications and will conduct surveys, interviews, and workshops with scientists to determine institutional barriers to the inclusion of and engagement with minorities in research. This project will draw from concepts of epistemic justice and anti-racism to develop ethical frameworks for BMH racial equity.Read moreRead less
The sexual cultures of Thai men; implications for Australia's international HIV/AIDS strategy. This project contributes to safeguarding Australia's national interests by supporting the implementation of AusAID's international HIV/AIDS strategy laid out in the policy document 'Meeting the Challenge: Australia's International HIV/AIDS Strategy' (2004). This project directly addresses research priorities identified in the analytical report for the White Paper on Australia's AID program, 'HIV/AIDS i ....The sexual cultures of Thai men; implications for Australia's international HIV/AIDS strategy. This project contributes to safeguarding Australia's national interests by supporting the implementation of AusAID's international HIV/AIDS strategy laid out in the policy document 'Meeting the Challenge: Australia's International HIV/AIDS Strategy' (2004). This project directly addresses research priorities identified in the analytical report for the White Paper on Australia's AID program, 'HIV/AIDS in the Asia Pacific Region' (AusAID 2005): (1) the cultural, economic, and political dynamics driving the HIV epidemic in Asia; (2) the nexus between HIV/AIDS, economic activity, and development; and (3) the Asian experience of feminisation and gender impacts as factors in the epidemic HIV in the region.Read moreRead less