Tissue Ferritin Acts As A Proinflammatory Mediator Of Hepatic Fibrosis In Chronic Liver Disease Via Multiple Receptors In Hepatic Stellate Cells Responsible For Both Binding And Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$777,887.00
Summary
Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology, the cells responsible for liver scarring (fibrosis) in Haemochromatosis. This proposal will identify the receptor responsible for eliciting ferritin's proinflammatory action and assess its role in fibrosis. This study will have implications in chronic liver diseases of varying aetiologies where elevated serum ferrritin is associated with inflammation.
Cellular Regulation Of Receptor Signalling And Cytokine Responses
Funder
National Health and Medical Research Council
Funding Amount
$859,288.00
Summary
Cell surface receptors and signalling pathways elicit the release of cytokines, or chemical messengers, to control inflammation, which is the body’s response to infection or danger. We have discovered a new signalling pathway that can turn off inflammation and help prevent inflammatory disease. Our studies will now define the molecular details of this pathway and show how new and existing drugs targeting this pathway can be optimally used to treat inflammation and cancer.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.
Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less
SARA: Delineating Its Association With The Onset And Development Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$865,972.00
Summary
Liver disease, a significant burden on society, affects many in the prime of their life. Scarring of the liver is a response to injury due to many factors including alcohol, viruses, obesity, and fatty-liver disease. We have identified a protein associated with liver injury. In this project we will perform a systematic analysis to understand the role of this protein in injury progression. Ultimately we intend to develop tools to prevent and treat liver injury.
Stem Cell Treatment For Neonatal Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$954,195.00
Summary
Hypoxic-ischaemic encephalopathy occurs when the fetus receives inadequate oxygen in labour and many babies die or have brain damage. Stem cell therapy might save these babies from brain damage but there are many unknowns, such as which stem cells to use and how many. Through our skills in stem cells and measuring the rescued brain following injury, we will determine the necessary details for the most effective stem cell therapy to be ready to immediately test the treatment in a RCT in babies.
A Novel Mesenchymal Stromal Cell And Biomaterial For Corneal Reconstruction
Funder
National Health and Medical Research Council
Funding Amount
$508,611.00
Summary
Our research group has identified a new cell type (L-MSC) with the potential to treat a variety of eye diseases. We have also developed a novel material from a protein found in silk, that has potential as a vehicle for delivering healthy cells into diseased eyes. The present project will build upon these promising results by evaluating the properties of L-MSC necessary for clinical use and by testing the feasibility of our new cell delivery system.
Functional Contribution Of Fetal Microchimeric Cells In Transgenic Models Of Maternal Tissue Repair In And After Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
Fetal stem cells cross into the mother during pregnancy and persist lifelong in her tissues. To determine whether helpful or harmful, we will study how these cells contribute to healing both after acute injury and in chronic genetic models like brittle-bone disease and muscular dystrophy. This research will inform long-term consequences of pregnancy, important for women's health and longevity, and help develop a promising form of stem cell therapy.
A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interac ....A Micro-Physiological System to Mimic Human Microbiome-Organ Interactions. This project aims to mimic gut microbiome-organ interactions by developing a microbial-gut coculture chip, which can reversibly interface with other organs-on-chips. This is achieved through the systematic integration of highly customisable biofabrication and microfluidic technologies. This project fills a critical technological gap in the availability of an animal-alternative system to investigate microbiome-host interactions, which will greatly complement existing meta-omics approaches. The deliverables include a proof-of-concept system validated for gut-liver axis as well as the creation of new knowledge and framework to assimilate design thinking and advanced manufacturing to elevate tissue engineering into physiology engineering. Read moreRead less