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Macrophage-regulated Tissue Remodelling In Endometrial Receptivity For Embryo Implantation And Pregnancy Success
Funder
National Health and Medical Research Council
Funding Amount
$456,779.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in th ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in the populations of immune cells called macrophages within the uterine endometrial lining can reduce the receptivity of the endometrum to embryo implantation, and can lead to fetal growth retardation and impaired health after birth. The purpose of this project is to delineate the precise functions of macrophages in interacting with other cells in the endometrium to facilitate attachment of the embryo, its invasion into maternal tissues, and its access to an adequate blood supply as the placenta develops during early pregnancy. We will employ state of the art experimental strategies including genetic models to deplete endometrial macrophage populations in mice, and will then study the implications for changes in endometrial tissue structure and function. Furthermore we will investigate the long term consequences of early macrophage perturbations for the fetus and neonate after birth. This study will improve our understanding of how determinants of macrophage function such as infection and inflammatory conditions, male factors, nutrition and stress can impair fertility and compromise optimal pregnancy outcome in humans.Read moreRead less
A Dendritic Cell Subset Targeting Approach For Generating Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$678,492.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Effective Immunotherapy For HPV Associated Cervical Cancer Precursor Lesions
Funder
National Health and Medical Research Council
Funding Amount
$482,640.00
Summary
Vaccines to prevent cervical cancer are currently being developed. These will be used to prevent infection with the causal virus, papillomavirus. However, there are very many people world wide who already have papillomavirus infection, which could turn into cancer at any point over the next 30 years. Therefore, there is a need for a vaccine that could be given along with the preventative vaccine, which would treat existing infections. This study addresses the characteristics of the immune respon ....Vaccines to prevent cervical cancer are currently being developed. These will be used to prevent infection with the causal virus, papillomavirus. However, there are very many people world wide who already have papillomavirus infection, which could turn into cancer at any point over the next 30 years. Therefore, there is a need for a vaccine that could be given along with the preventative vaccine, which would treat existing infections. This study addresses the characteristics of the immune response required to treat existing papillomavirus infections, since this is not currently known.Read moreRead less
Phenotypic And Functional Characterization Of Human Dendritic Cell Subsets Generated In Vitro And Isolated From Tissues
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The immune system defends us against infections and cancer. Dendritic cells (DC) are white blood cells that have a central role to both activate the immune system and to regulate immune responses. In this study, we will determine the functional differences of human DC populations, because a clear understanding of the functional differences between different human DC types is essential for utilizing DC in designing more effective vaccines and immune therapies for clinical applications.
Development And Function Of NKT Cell Subsets In Humans
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This ....NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This lack of knowledge has prevented us from understanding how NKT cells normally prevent disease, and how we should treat diseases associated with low NKT cell numbers. In this project, we will study human NKT cells to determine how many different subsets exist, how they develop, and what role they play in the immune system. Importantly, we will use our knowledge to compare NKT cells from healthy donors and patient groups with T1D and cancer to determine exactly what is wrong with the NKT cells in these people. While both diseases are already linked to low NKT cell numbers, we do not know how these problems arise, or if some types of NKT cells are more important than others. Our study will determine how different types of NKT cells develop and function in humans and therefore allow a much more detailed understandng of how to diagnose and treat NKT cell deficiencies associated with different diseases.Read moreRead less
Direct Characterisation Of Naive Epitope-specific T Cell Populations And Their Influence On Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$314,983.00
Summary
CytotoxicT cells (CTLs) recognize and remove virus infected cells. Both the number and the diversity of T cells involved in the response influence viral clearance. We plan to use a novel technology to directly analyze the numbers and diversity of such CTLs in mice prior to infection. This will clarify how characteristics of cell populations prior to infection define the immune response after infection. This is critical for vaccine design to maximize the efficiency of the immune response.
Understanding Immune Tolerance In Pregnancy To Discover A New Intervention For The Treatment Of Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$492,202.00
Summary
Pre-eclampsia is a common complication of pregnancy. Women who develop pre-eclampsia experience high blood pressure, swelling and lose protein in the urine. There is no treatment for pre-eclampsia other than delivery of the baby. Pre-eclampsia has risks for the mother and the baby. This research will discover whether generalised inflammation in the mother is a cause of pre-eclampsia and will evaluate the role of a novel treatment for its potential to prevent this life threatening condition.