The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
This application seeks information on the factors controlling T cell survival, tolerance and responsiveness to foreign antigens and tumour antigens. Particular attention will be directed to determining how T cells are kept alive through contact with self ligands and cytokines while preserving self tolerance and how anti-tumour responses can improved without augmenting the function of T regulatory cells.
Cancer is one of the leading causes of death in the industrialized world. While therapies to treat cancer have continued to improve one area that, in theory at least, shows great promise in the treatment of tumours is manipulating the immune system to effectively recognize and destroy cancerous lesions. Experiments in human and animal systems have clearly shown that the immune system has the potential to respond to tumour cells and trials of tumour vaccines are underway. It has recently become a ....Cancer is one of the leading causes of death in the industrialized world. While therapies to treat cancer have continued to improve one area that, in theory at least, shows great promise in the treatment of tumours is manipulating the immune system to effectively recognize and destroy cancerous lesions. Experiments in human and animal systems have clearly shown that the immune system has the potential to respond to tumour cells and trials of tumour vaccines are underway. It has recently become apparent that the immune responses to tumours may be inhibited by classes of regulatory immune cells. Eliminating these cells results in a more vigorous and effective anti-tumour response. This project will seek to discover the mechanisms of action of theses regulatory immune cells in order to devise more effective anti-cancer vaccines and therapies.Read moreRead less
Identifying T Cell Correlates Of Protective Immunity To Malaria In Childhood
Funder
National Health and Medical Research Council
Funding Amount
$396,026.00
Summary
Malaria claims nearly one million lives each year, mostly children. Although those living in endemic regions can acquire natural immunity, it develops slowly and isn`t completely protective. This project studies the impact of different levels of malaria exposure and age on the development of a protective immune response in children. By understanding the effect of high malaria exposure in the development of immunity it is hoped that new avenues for drug development may be identified.
This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicat ....This application proposes to study in detail the main target cell for HIV infection, namely CCR5+ CD4 T lymphocytes. After 30 years of the pandemic, fundamental knowledge of these cells, such as locations in the body, differentiation from other lymphocytes, and survival, is still lacking. These attributes determine whether or not they will be infected by HIV, whether this can be prevented by vaccines or CCR5 blocking drugs, and whether their long-term survival results in an inability to eradicate HIV.Read moreRead less
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Cancer immunotherapy by “checkpoint blockade” boosts the immune response and leads to tumour rejection in some patients. To improve immunotherapy, information will be sought on the capacity of membrane vesicles prepared from dendritic cells (DC) to stimulate immune cells (T cells) in mice and elicit tumour rejection. Experiments are proposed to trace the fate of the vesicles after injection and improve tumour rejection by combination with checkpoint blockade and addition of cytokines.