Polarity Regulation In T Cells: Mechanisms And Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Advances in our understanding of how the immune system works have led to many breakthroughs in healthcare, including organ transplantation, management of autoimmune diseases and immunodeficiencies such as AIDS. To improve these treatments, we need a better understanding of how the immune system is controlled. This proposal explores the mechanisms by which immune cell signalling is regulated by spatial compartmentalisation within the cell.
The Role Of Transcription Factors In Regulating The First Round Of Gene Expression In The Early Embryo.
Funder
National Health and Medical Research Council
Funding Amount
$348,931.00
Summary
Assisted reproductive technologies result in a high incidence of multiple births. This is and adverse outcome that requires correction. It stems from the common transfer of several embryos due to the low chance of an individual embryo made by IVF resulting in a baby. This project will determine the normal pattern of gene expression in the embryo and define: (1) how it is adversely changed as a consequence of IVF; and (2) the extent that these changes are a cause of the low embryo viability.
Mechanisms Of P53 Induced Embryopathy After In Vitro Fertilisation.
Funder
National Health and Medical Research Council
Funding Amount
$483,737.00
Summary
Assisted reproductive technologies (ART) cause many embryos not to survive to birth. We have shown that IVF causes increased expression of protein normally involved in stopping cells from dividing. This is a major cause of embryo death after IVF. This project will determine how this protein acts to cause embryonic death and assess strategies to prevent it.
In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less
CTL Avidity As A Determinant Of The Mature, Antigen-specific Immune Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$241,527.00
Summary
Killer T lymphocytes are a diverse population which vary in their ability to recognise infected cells. This study aims to determine whether vaccine dose and frequency impact on the generation of highly sensitive killer T cells. This study will improve our basic knowledge of killer T lymphocyte selection during infection and have application to improved methods of vaccination.
The normal processes of development of the embryo require that the information encoded in chromosomes be reprogrammed soon after fertilization. This process is rather fragile and disturbance of the early embryo can upset it. Recent studies for the chief investigator's provide new understanding of the normal processes of reprogramming. The project will explore and validate the implications of these new discoveries and provide a basis for future alleviation of abnormalities to development.
Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and ....Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and cellular events associated with periodontal regeneration. Despite efforts to induce regeneration through the selective use of growth and differentiation factors it is becoming obvious that the most significant factor in successful clinical outcomes is the recruitment of special cells to the site of damage which have the potential to repair tissue damage. Thus, we intend to engineer different types of periodontal matrices in the laboratory and then transplant these newly formed tissues into sites affected by periodontal disease in an attempt to repair the damage caused by the disease process.Read moreRead less
Improved Vaccines Against Tuberculosis Based On Dendritic Cell Manipulation
Funder
National Health and Medical Research Council
Funding Amount
$257,036.00
Summary
The incidence of tuberculosis (TB) is increasing throughout the world. BCG, the only currently available vaccine is only partially protective and better vaccines are urgently required to help limit the spread of TB. We have recently prepared naked DNA vaccines with the genes for three mycobacterial proteins and found that they partially protected against lung TB in mice. Further improvement is required and this project is to design and test improved DNA vaccines. Vaccines will be more effective ....The incidence of tuberculosis (TB) is increasing throughout the world. BCG, the only currently available vaccine is only partially protective and better vaccines are urgently required to help limit the spread of TB. We have recently prepared naked DNA vaccines with the genes for three mycobacterial proteins and found that they partially protected against lung TB in mice. Further improvement is required and this project is to design and test improved DNA vaccines. Vaccines will be more effective if they generate stronger cellular immune response to mycobacteria. Dendritic cells (DC) are the major cells that present mycobacterial antigens to T lymphocytes and thus stimulate T lymphocytes to generate immune responses that protect against TB. Therefore the aim of this project is to identify ways to manipulate DC to improve their ability to activate protective immunity. We will target membrane molecules on DC to activate the antigen- presenting function of these cells by fusing the genes for mycobacterial proteins to genes either for antibodies to surface molecules on DC or receptors for these molecules. These novel DNA vaccines will be tested for their effects on DC function and their capacity to stimulate the protective pattern of immunity in mice. The cytokine environment at the time of stimulation will be modified by giving the DNA vaccine together with two cytokine-expressing vaccines, to 'push' the T lymphocytes to respond more vigorously. Finally, we shall test whether a combination of the new DNA vaccines and BCG is more effective than BCG at protecting against virulent TB infection.Read moreRead less