Self Adjuvanting CTL-Based Influenza Vaccines For Human Use
Funder
National Health and Medical Research Council
Funding Amount
$214,842.00
Summary
This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recog ....This project will generate novel vaccines that elicit cell-mediated immunity against influenza infection. The vaccines are totally synthetic and therefore not constrained by the limitations in manufacturing which currently confront egg-grown vaccines. These vaccines induce very strong immune responses because they target dendritic cells which are pivotal for induction of all immune responses. This targeting capability is due to a simple lipid molecule incorporated into the vaccine which is recognised by specific receptors on the surface of dendritic cells and also causes their maturation, a step which is essential for recognition by the immune system of potential pathogens. The technology to design and assemble these new vaccines is already.Read moreRead less
They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid ....They aim to create insulin-secreting B cells by identifying their progenitor cells and the moleculaes normally required for their development, in order to restore B-cell function in the people with type 1 diabetes. Mouse and human multipotent embryonic stem (ES) cells and fetal mouse panceas and adult pancreas duct cells will be used as sources of progenitor B cells. Comparative studies will provide a more complete picture of human B-cell ontogeny. Culture systems developed for ES cells-embryoid bodies (EB) - EB-derived cells, fetal pancreas and adult pancreas duct cells, will be employed to screen for and identify novel growth-differentiation factors and to optimise parameters for creating B cells in vitro or (re) generating B cells in vivo. Genetic constructs allowing regulated expression of fluorescently-tagged marker genes and growth-transcription factors will be introduced into cultured cells or transgenic mice to enable progenitor B cells to be tracked and isolated. Progenitor B cells will be typed with panels of known novel markers molecules at the gene and protein level, and gene expression profiles of tissue yielding B cells will be analysed across time to reveal further candidate markers. Molecules and methods effective in mouse systems will be applied to human ES cell-derived or pancreatic duct cells. The capacity to progenitor cells or insulin-secreting cells to ameliorate diabetes when transplanted into the testis, under the kidney capsule or into the pancreas of mouse models would represent proof-of-concept. Functional B cells derived from human ERS cells or pancreas duct cells, or growth factors that regenerate B cells in vivo, could together with appropriate immunotherapy restore B-cell function in people with type 1 diabetes.Read moreRead less
Loss of insulin-producing beta cells leads to type 1 diabetes and rejection of allogeneic islet transplants. The aim of this program is to discover ways of protecting beta cells from damage. We will do this by investigating whether blocking crucial regulators of cell death can protect mouse and human beta cells from destruction in vitro and in vivo. In doing so, we aim to prevent diabetes in mice and potentially improve the survival of islet grafts after transplantation.
HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein transla ....HIV infection of CD4+ lymphocytes leads to a high rate of reproduction of new virus. However, in the brain, HIV infection of the astrocytes does not yield high levels of new virus. HIV is genetically active in these astrocytes, producing high levels of the messenger molecules, the so-called mRNA, that code for the proteins required for a new virus particle. We have determined that these HIV mRNAs are specifically prevented from translating into protein. The mechanisms controlling protein translation from RNA are relatively poorly understood compared with the other control points of cellular gene expression, such as the synthesis of mRNA. This project examines how astrocytes rapidly detect the presence of HIV mRNA and alter their translation machinery to halt the expression of HIV protein. This host defence mechanism involves two key components; the cellular component that identifies and responds to the viral mRNA, and the structural features of the HIV mRNA that enable the cell to detect its viral origin. We will study how translation of HIV proteins requires both HIV and cellular factors. We will determine the impact of both viral RNA elements and viral RNA binding proteins on the translation of viral and cellular proteins. The contribution of the type-1 interferons that are produced in response to viral infection will be studied for their role in augmenting the inhibition of HIV protein translation. Since HIV infected astrocytes significantly contribute to the onset of AIDS dementia, we will sees a strategy to lock HIV into a dormant state in the brain and thereby prevent the neurodegenerative disease associated with HIV. We will use the anti-viral mechanism blocking HIV protein translation in astrocytes to protect other cell populations, such as the CD4+ lymphocytes, from HIV infection. These studies will also give insights into the general mechanisms for translational control of gene expression in human cells.Read moreRead less
Enterovirus 71 In The Asia-Pacific Region: Reverse Genetic Approaches To Virus Surveillance And Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$690,833.00
Summary
In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop ....In this research the team will use advanced biotechnological techniques to study the distribution and virulence markers of an important emerging infectious disease, enterovirus 71 encephalitis, in the Asia-Pacific region. The knowledge and technical advances derived from this study will be shared with neighbouring countries in order to conduct sensitive surveillance for this infection throughout the region. The study's other major aim is to use cutting-edge biotechnological techniques to develop a genetically defined, live attenuated vaccine strain. Candidate vaccine strains will be tested for their effectiveness in both cell culture-based and animal models.Read moreRead less
A Study To Pilot A Clinical Trial To Test Dignity Psychotherapy For The Frail Aged
Funder
National Health and Medical Research Council
Funding Amount
$25,000.00
Summary
One of the greatest challenges today is to preserve the dignity of the frail elderly. Our study will test and perfect a strategy to trial a new approach for this population, Dignity Psychotherapy. The approach will document aspects of the senior's life that they regard as meaningful, want remembered, or of which they are proud. Among the terminally ill, the approach has had positive outcomes. Benefits for elders may include that the approach forms a foundation for holistic care.
Person-centred Environment And Care For Residents With Dementia: A Cost-effective Way Of Improving Quality Of Life And Q
Funder
National Health and Medical Research Council
Funding Amount
$1,548,805.00
Summary
Improving the quality of life (QOL) and quality of care for persons with dementia are important areas of Australian health research. A growing body of evidence shows that QOL in dementia can be improved by relatively simple and inexpensive modifications to nursing care practices and the physical environment. Most studies in these areas are observational, few have utilized a randomized control group design, and none has included economic evaluation. This study will address these deficiencies. Thi ....Improving the quality of life (QOL) and quality of care for persons with dementia are important areas of Australian health research. A growing body of evidence shows that QOL in dementia can be improved by relatively simple and inexpensive modifications to nursing care practices and the physical environment. Most studies in these areas are observational, few have utilized a randomized control group design, and none has included economic evaluation. This study will address these deficiencies. This is the first time that a randomized controlled trial of Person-Centred Care (PCC) and Person-Centred Environment Design (PCD) will be undertaken. The study will be conducted in 40 residential aged care services in New South Wales, to determine the efficacy and cost effectiveness of implementing PCC and PCD separately, and in combination, in improving resident quality of life and quality of care.Read moreRead less