The Astrocyte: A Crossroads In Cerebral Malaria Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Malaria is an infectious disease that kills over 1 million people each year. It is prevalent in the Australian region, e.g. PNG and SE Asia. One of its most serious complications is cerebral malaria (CM), which affects the brain and is often fatal. This project will determine whether a very important cell in the brain, the astrocyte, is involved in the disease processes that lead to CM. This is highly relevant to the development of therapies that can be given along with anti-malarial drugs.
Treating and preventing painful fractures could be improved by strengthening cortical bone – the hard outer shell of all bones in the skeleton. We don’t know how cortical bone forms, but if we did, we could improve its strength. We have found that a brain-like network of cells inside the skeleton, called osteocytes, use a specific signal, called SOCS3, to make strong cortical bone. This study will find out how SOCS3 works and find new ways to make cortical bone strong and healthy.
Preclinical Evaluation Of A Novel Allosteric IL-1R Inhibitor (rytvela) For The Prevention Of Perinatal Inflammation-induced Fetal Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,377,827.00
Summary
Interleukin-1 (IL-1) is a potent inflammatory protein involved in many inflammatory disorders, including preterm birth (PTB). Blocking the actions of IL-1 in pregnancies at risk of delivering preterm may protect the fetus from PTB and the long-term harm of exposure to inflammation before birth. Using four different models of antenatal inflammation, we will explore the use of a new IL-1 inhibitor to see if it blocks inflammation ‘in utero’ and improve neonatal health and development.
B Cells And Autoantibodies In The Pathogenesis Of Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$853,340.00
Summary
This project aims to gain a better understanding of the causes of hypertension. Specifically, we will test the idea that activation of the immune system and the production of antibodies is a major cause of the blood vessel and kidney damage that leads to high blood pressure. Such findings could pave the way for new treatment approaches where drugs currently reserved for patients with autoimmune diseases (e.g. rheumatoid arthritis, gout) are re-purposed for the treatment of hypertension.
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Modulation Of TGF-beta Signaling By CDA1 In The Diabetic Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$524,004.00
Summary
Cell Division Autoantigen 1 (CDA1) is a molecule we identified several years ago. Recently we found that CDA1 played an unique role in causing blood vessels to scar and become stiff by hijacking and controlling the existing transforming growth factor-beta (TGF-beta) signaling pathway. We will explore the possibility to use this unique property of CDA1 to treat the blood vessel hardening and related diseases such as atherosclerosis and heart attacks, particularly in the setting of diabetes.
Understanding And Applying Macrophage-mediated Effects On Liver Progenitor Cells To Treat Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$628,109.00
Summary
As liver cancer risk correlates with increased liver stem/progenitor cell numbers, therapies that reduce their numbers will reduce cancer development. On the contrary, therapies to increase progenitor cell numbers will assist their use in cell therapy-based approaches or artificial liver devices to treat chronic liver disease. This project will determine how to use inflammatory cells to manipulate progenitor cell numbers.
Chemerin, A Novel Therapeutic Target For Modulation Of Adipose Tissue Mass
Funder
National Health and Medical Research Council
Funding Amount
$535,621.00
Summary
Obesity is a significant public health issue due to its increasing prevalence and association with other diseases including cardiovascular disease. Efforts to pharmacologically prevent and treat obesity are impaired by an incomplete understanding of the genes and metabolic processes involved. This project will use cell and animal models to examine the processes that occur during the expansion of fat tissue which will broaden our understanding of obesity and assist in identifying new therapies.
Age-dependent Regulation Of Type 2 Immunity By Dermal Innate Lymphoid Cells
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
Type 2 immune responses are critical for the defense against worm infections, but can also cause allergic reactions. How type 2 immunity is regulated is poorly understood. The aim of this application is to define the function of a newly discovered skin immune cell population, dermal type 2 innate lymphoid cell, in cutaneous worm infections and allergies. We anticipate that our studies will aid in the development of strategies to prevent or treat skin allergies and parasitic infections.
Physiological Mechanisms Of Experimental Preeclampsia.
Funder
National Health and Medical Research Council
Funding Amount
$471,862.00
Summary
Defining the sequence of abnormalities of immune system regulation and vascular reactivity would greatly enhance our understanding of the underlying mechanisms of preeclampsia (hypertension in pregnancy) and lead to opportunities for definitive treatment for the mother and baby other than by urgent delivery of the pregnancy. Results from this study may lead to tests in early pregnancy of the hypoxic environment such as cytokine imbalance.