Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Triggering the dormant capacity of fish to make omega 3 fatty acids. Marine fisheries cannot expand further, leaving aquaculture (fish farming) with the challenge of meeting the growing demand for fish, whose consumption is known to enhance human health. Fish oil is an essential component of the feed used in aquaculture, but there is a decreasing global supply of this commodity. This innovative nutritional biochemistry project boosts the capacity of fish to produce their own fish oil from vegeta ....Triggering the dormant capacity of fish to make omega 3 fatty acids. Marine fisheries cannot expand further, leaving aquaculture (fish farming) with the challenge of meeting the growing demand for fish, whose consumption is known to enhance human health. Fish oil is an essential component of the feed used in aquaculture, but there is a decreasing global supply of this commodity. This innovative nutritional biochemistry project boosts the capacity of fish to produce their own fish oil from vegetable oils in their diet. Therefore, this project will enable the expansion of aquaculture as an economically and environmentally sustainable means to produce the highest quality, nourishing fish for human consumption.Read moreRead less
The effect of dietary fish peptides on biomarkers of human health - the influence of processing conditions and the environment. This project links together two diverse but important areas of national importance: declining fisheries and human health. Australia is a small producer and exporter of fish but has access to significant fisheries. The Geelong Food Co-product Cluster comprises a number of fish companies facing serious problems associated with declining catches compounded by the current f ....The effect of dietary fish peptides on biomarkers of human health - the influence of processing conditions and the environment. This project links together two diverse but important areas of national importance: declining fisheries and human health. Australia is a small producer and exporter of fish but has access to significant fisheries. The Geelong Food Co-product Cluster comprises a number of fish companies facing serious problems associated with declining catches compounded by the current financial crisis. Increasing use of by-catch species and developing novel processing technology for controlled release of bioactive peptides that may reduce appetite and the tendency for overweight and obesity in consumers could provide the Australian seafood industry with a world competitive innovative technology leading to improvements in human health.Read moreRead less
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
Omega-3 fatty acids, appetite and growth in farmed fish. Australia has very limited wild fish supplies, and with the increasing realization of human health benefits of fish (i.e. omega-3 fatty acid) there is a need to increase availability through aquaculture. However, feeds used in aquaculture contain costly fish oil with limited global supplies. Attempts made to substitute fish oil with vegetable sources in aquaculture feeds have been mixed. This international, comparative and multidisciplinar ....Omega-3 fatty acids, appetite and growth in farmed fish. Australia has very limited wild fish supplies, and with the increasing realization of human health benefits of fish (i.e. omega-3 fatty acid) there is a need to increase availability through aquaculture. However, feeds used in aquaculture contain costly fish oil with limited global supplies. Attempts made to substitute fish oil with vegetable sources in aquaculture feeds have been mixed. This international, comparative and multidisciplinary project aims to reduce the dependence on fish oils through investigation of basic fatty acid metabolism and endocrinology on farmed fish to ensure that human health promoting characteristics in the final product are retained.Read moreRead less
Natriuretic peptide hormones and the stress response of fish. There are two main benefits of our research to Australia. Firstly, the team that we have assembled have international reputations, and include scientists from overseas. This team will be led by Australian Institutions and will put Australian science in the forefront of a competitive field, internationally. Secondly, our research examines questions that are critical in our understanding of how animals respond to stressful events. T ....Natriuretic peptide hormones and the stress response of fish. There are two main benefits of our research to Australia. Firstly, the team that we have assembled have international reputations, and include scientists from overseas. This team will be led by Australian Institutions and will put Australian science in the forefront of a competitive field, internationally. Secondly, our research examines questions that are critical in our understanding of how animals respond to stressful events. The response to stress, if excessive, leads to ill-health in both humans and other animals. Our research examines new connections between stress and fish biology, which could lead to discoveries that are valuable in managing stress and health in wild and farmed fishes.Read moreRead less
Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to p ....Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to produce the phenotype by defining the critical period and systematically identifying genes that are expressed during this period. The effect of manipulating maternal dietary omega-3 PUFA and the role of angiotensin will then be examined. The project will discover how genetic, hormonal and environmental factors interact during the perinatal period of life to program food intake and body weight in adult life. Read moreRead less
Phylogeography, Conservation Genetics and Stocking Management of Perches and Basses. This project will use DNA data to address fundamental questions about the origin and maintenance of biodiversity in a popular and widely distributed fish group. From a conservation perspective, the project will produce a benchmark about management of fish resources. We will investigate questions related to important conservation issues (including the recovery plan of a nationally threatened species) and the mana ....Phylogeography, Conservation Genetics and Stocking Management of Perches and Basses. This project will use DNA data to address fundamental questions about the origin and maintenance of biodiversity in a popular and widely distributed fish group. From a conservation perspective, the project will produce a benchmark about management of fish resources. We will investigate questions related to important conservation issues (including the recovery plan of a nationally threatened species) and the management of stocking activities in recreational fisheries of coastal and inland waters. The latter is particularly relevant to rural communities since they provide both social and economic benefits to rural people.Read moreRead less
Automation of species recognition and size measurement of fish from underwater stereo-video imagery. The project aims to develop algorithms to automate the processing of stereo-video images recorded to count and measure the size of fish. This will improve husbandry and monitoring for finfish aquaculture at reduced costs, create technology export for industry partners, and develop cost effective, non-destructive finfish sampling tools for marine agencies.
Lost at sea? Understanding adaptation and dispersal in spiny lobsters. Continual recruitment of young is fundamental to the replenishment of populations, especially when a stock is fished. Existing theory suggests that species with very long planktonic larval stages disperse widely, ensuring their genes are well mixed. However, recently identified genetic differences between populations of rock lobster challenge this paradigm and demonstrate that despite larvae mixing in the ocean for years, loc ....Lost at sea? Understanding adaptation and dispersal in spiny lobsters. Continual recruitment of young is fundamental to the replenishment of populations, especially when a stock is fished. Existing theory suggests that species with very long planktonic larval stages disperse widely, ensuring their genes are well mixed. However, recently identified genetic differences between populations of rock lobster challenge this paradigm and demonstrate that despite larvae mixing in the ocean for years, local recruitment and/or adaptation are at play. Recent developments in genomics and bioinformatics should allow this project to understand the ecological processes underpinning these genetic signatures and determine their evolutionary implications. Such findings could direct targeted rebuilding of depleted fisheries stocks.Read moreRead less