When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Microenvironmental Regulation Of Blood Cells By Retinoic Acid Receptor Gamma.
Funder
National Health and Medical Research Council
Funding Amount
$958,428.00
Summary
Vitamin A deficiency causes profound effects in humans, with anaemia and an inability to fight infection being consequences of vitamin A deficiency on blood cells. We have evidence that these effects of vitamin A deficiency occur via one of the receptors for vitamin A. Furthermore, these effects are due to changes in the non-blood cells that help to make blood cells. By understanding how this occurs we may identify better treatments for patients with impaired immune systems.
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 Role Of EphrinB1 Reverse Signalling In Osteogenic Differentiation During Skeletal Development And Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$567,292.00
Summary
The present proposal will identify the importance of ephrinB1 during the deregulation of bone remodelling that occurs in osteoporosis, by deleting ephrinB1 in committed osteoblast precursor cells in a mouse model of osteoporosis. Knowledge gained from this proposal could potentially translate into alternative therapeutic treatment strategies for patients with osteoporosis with the use of Eph/ephrin targeted drugs currently being developed for cancer treatment.
B1a B Cells: Atheroprotective Mechanisms And Therapeutic Application
Funder
National Health and Medical Research Council
Funding Amount
$547,180.00
Summary
Atherosclerosis-related heart attacks and strokes remain leading causes of global deaths despite use of potent lipid-lowering drugs. Thus, another therapeutic option is urgently needed. Our laboratory found that B1a B cells protect against atherosclerosis. We will study the therapeutic efficacy of expanding B1a cells by different approaches in atherosclerosis. Our proposal for clinical translation is to reduce mortality from atherosclerosis-based heart attacks and strokes.
Novel Posttranscriptional Pathways The Control Tfh Cell Numbers
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
T follicular helper (Tfh) cells are essential for effective antibody responses against infection. Limiting Tfh cells is crucial for selecting the "fittest" B cells and the success of vaccines. Tfh cell accumulation causes autoimmuity and is associated with inadequate B cell responses in HIV infection. We have recently discovered two novel pathways that control Tfh cells. We speculate they regulate different RNAs that influence Tfh homeostasis and aim to elucidate their mechanism of action.
Targeting Antigen To Clec9A On Dendritic Cell For Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$744,624.00
Summary
Dendritic cells capture infectious organisms and display them to other immune cells to initiate immunity. The process of capturing organisms requires dendritic cells to express a variety of cell-surface receptors that detect components carried by infectious agents. Here we will examine the efficacy of attaching vaccine components to a targeting agent that binds one of these receptors with the aim of enabling dendritic cells to efficiently kick-start immunity against vaccine components.
The immune system must be tightly regulated to make sure that it makes the right response to effectively fight off infection whilst avoiding inappropriate responses that cause damage such as in autoimmunity, inflammation or allergy. This project studies patients who have genetic defects that affect their immune systems and make them susceptible to infection and/or harmful immune responses. This will reveal some of the critical signals that maintain immune control.
Methylation Sensitive Genes And The Transition To Allergic Disease: A Twin Study
Funder
National Health and Medical Research Council
Funding Amount
$493,843.00
Summary
Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in ....Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in children.Read moreRead less