Physiological Function Of The Novel Vitamin D Receptor Isoform
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form s ....Vitamin D regulates a wide range of physiological systems including those involved in control of calcium blood level and bone health as well as regulation of the immune system and of cell growth. Vitamin D action is mediated through the vitamin D receptor (VDR), a member of a large family of proteins that regulate the activity of specific target genes that control numerous biological functions. A novel, larger form of the human VDR has recently been described in our laboratory. This novel form shows differences in activity from the shorter VDR form (VDRA) and also has an unusual distribution within the nucleus of the cell that may relate to its function. The present project focuses on further analysis of the relevance of this novel VDR isoform to normal physiology. We hypothesise that the larger VDR isoform has unique characteristics that may modify how vitamin D works in different cells and tissues, on specific target genes and in response to different active forms of vitamin D. These differences depend on this novel isoform s interaction with specific nuclear proteins that regulate the actions of other hormone receptors. The specific aims of this project are to study the functions of the novel VDR isoform in comparison to VDRA: * On different target genes that are either activated or inhibited in response to vitamin D, and on different cell lines from tissues where vitamin D has important roles, like intestine, kidney and bone * In their response to natural and synthetic vitamin D compounds, because of their possible therapeutic applications * In their interactions with intranuclear regulatory proteins, to understand the underlying mechanisms The study of these two forms of the VDR will help to clarify their potentially different cellular roles and their contribution to the wide range of physiological processes regulated by the vitamin D endocrine system. This understanding may open new paths for treatments of human bone and calcium-related diseases.Read moreRead less
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
SCRC: The SIPP Program - Connecting Early Career Researchers With The Australian Seafood Industry Through Meaningful Coaching Partnerships: Year 2
Funder
Fisheries Research and Development Corporation
Summary
Disconnection between research and commercial sectors are a real challenge for the seafood industry as a whole. This disconnection leads to lack of communication about research needs from industry and poor adoption of research outcomes. Consultation with industry has identified a need for more industry ready graduates who have a deeper understanding and connection with the Australian seafood industry and understand more thoroughly the nature and the challenges commercial facilities face in all f ....Disconnection between research and commercial sectors are a real challenge for the seafood industry as a whole. This disconnection leads to lack of communication about research needs from industry and poor adoption of research outcomes. Consultation with industry has identified a need for more industry ready graduates who have a deeper understanding and connection with the Australian seafood industry and understand more thoroughly the nature and the challenges commercial facilities face in all facets of their business.
In addition, there is a need to enhance two way communication and cooperation between industry and research providers. The CRC SIPP program will assist in improving that process by enabling opportunities for industry and researchers to understand each other’s views, challenges and promote better communication on ideas and projects.Read moreRead less
Review the preconditions and the underpinning industry and government structures necessary for the successful implementation of co management Objectives: 1. To investigate the resilience of the various co-management approaches to a changing fishing operational environment (biophysical and socio-governance) 2. To look at the lessons learnt, and the challenges arising from, the implementation of co-management in all jurisdictions; with a view to identifying positive and negati ....Review the preconditions and the underpinning industry and government structures necessary for the successful implementation of co management Objectives: 1. To investigate the resilience of the various co-management approaches to a changing fishing operational environment (biophysical and socio-governance) 2. To look at the lessons learnt, and the challenges arising from, the implementation of co-management in all jurisdictions; with a view to identifying positive and negative drivers 3. To assess the skill sets needed to successfully implement co-management 4. To assess how to resource co-management once the fishery has moved past the RD&E phase 5. To identify the relevant RD&E questions to inform future investment 6. To document recommendations for the future implementation of co management Read moreRead less
Aquatic Animal Health Subprogram: Technical Guidelines For The Translocation Of Live Aquatic Animals
Funder
Fisheries Research and Development Corporation
Funding Amount
$18,000.00
Summary
There is an existing National Policy for the Translocation of Live Aquatic Organisms. published by the Ministerial Council of Forestry, Fisheries and Aquaculture (1999). This provides the policy basis for translocation within Australia. Industry concern about the practical processes for achieving translocation approval lead to the funding of FRDC 2002/080. In addition, recent concern among jurisdictions over VER outbreaks has emphasised the need to develop technical guidelines to underpin test ....There is an existing National Policy for the Translocation of Live Aquatic Organisms. published by the Ministerial Council of Forestry, Fisheries and Aquaculture (1999). This provides the policy basis for translocation within Australia. Industry concern about the practical processes for achieving translocation approval lead to the funding of FRDC 2002/080. In addition, recent concern among jurisdictions over VER outbreaks has emphasised the need to develop technical guidelines to underpin testing, as well as policy guidelines, for finfish. Objectives: 1. To progress a common approach to the translocation of live finfish across Australia for aquaculture and restocking purposes. Read moreRead less
Aquatic Animal Health Subprogram: Development Of Diagnostic Tests To Assess The Impact Of Haplosporidium Infections In Pearl Oysters
Funder
Fisheries Research and Development Corporation
Funding Amount
$133,716.59
Summary
One of the key objectives of the WA Department of Fisheries Business Plan is to ensure ecological and environmental sustainability of the pearling industry. The proposed project will be of direct benefit to the Western Australian pearling industry in that it will document the existence, if any, of the Haplosporidium and its effect on Australia’s most important commercial pearl oyster species.
Given the difficulties in detection and identification of Haplosporidium by current techni ....One of the key objectives of the WA Department of Fisheries Business Plan is to ensure ecological and environmental sustainability of the pearling industry. The proposed project will be of direct benefit to the Western Australian pearling industry in that it will document the existence, if any, of the Haplosporidium and its effect on Australia’s most important commercial pearl oyster species.
Given the difficulties in detection and identification of Haplosporidium by current techniques (histology and light microscopy), there is a need for alternative, reliable, and cost-effective methods for detecting and speciation of Haplosporidium.
In the context of a pearling industry that is undergoing a process of intensification in which disease management continues as a priority issue, this lack of basic diagnostic capability needs to be addressed.
Such diagnostic tools will help assess the parasite’s impact on the pearl oyster and its potential threat to the industry, as well as providing tools to assist in diagnosis, epidemiology and surveillance of disease. This could be of key importance in trying to determine the true geographic extent of the parasite, to assess why the outbreaks have been sporadic in nature, and to assist in the early detection and management of possible future outbreaks.
In addition, there is an international shortage of pathologists with expertise in molluscan pathology and a national need for research projects that are suitable for the postgraduate training of aquatic animal health specialists.
The FRDC Aquatic Animal Health Subprogram (AAHS) and Scientific Advisory Committee has reviewed the preliminary research proposal and assessed it as high priority. Objectives: 1. To develop a PCR test that is sensitive and specific, being able to detect Haplosporidia generally, yielding a product that is suitable for sequencing and determination of the species. 2. To sequence amplified genomic segments, obtained by PCR, from infected pearl oysters, to determine the species and its phylogenetic relationships. 3. Once sequence data are obtained (from 1), to develop a PCR test that specifically detects only the Haplosporidian species in pearl oysters. 4. To use sequence data obtained in (2), to document the location and distribution of the parasite within the oyster, by the development and application of in situ hybridisation, as part of a study on its life cycle and biology, in conjunction with routine light microscopy. In situ hybridisation is also key in confirming PCR test results. 5. To determine, retrospectively, the molecular identity of the Haplosporidian involved in the previous outbreaks, to see if the same isolate was involved in all outbreaks. 6. To determine whether the parasite is still present in the original outbreak sites and in other sites not historically affected, by the deployment and assessment of spat in these locations. 7. To develop a means for the assessment of infectivity and pathogenicity using rock oysters and their endemic Haplosporidium as a model. Read moreRead less
Application Of Protein Microarrays To Develop A Cross-Species Malaria Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$451,821.00
Summary
Malaria remains a significant public health problem worldwide. Five species of malaria parasites infect humans. The ideal vaccine would be effective against all five species. Using a novel protein microarray approach, we will identify Plasmodium proteins that may be excellent targets of a cross-species malaria vaccine. This research will build on Australia's current strengths in biotechnology and will result in significant economic benefits by facilitating the development of a malaria vaccine.