Characterising Signals Important For Lymphangiogenesis During Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$604,938.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including cancer, lymphoedema and inflammatory diseases. The focus of this application is to characterise signals that direct the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Defining The Role Of GATA2 In Lymphatic Vascular Development As A Means To Understanding How GATA2 Mutations Predispose To Human Lymphedema.
Funder
National Health and Medical Research Council
Funding Amount
$718,890.00
Summary
We have discovered that mutations in the transcription factor GATA2 result in human primary lymphedema, a debilitating disorder resulting from the failure of lymphatic vessels to return tissue fluid to the bloodstream. The goal of this application is to define the role of GATA2 in lymphatic vessels, in order to understand how GATA2 mutations cause lymphedema. Ultimately, we aim to identify targets to which desperately needed therapeutics for the treatment of lymphedema could be generated.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Novel Methods For Promoting Organ Development And Growth
Funder
National Health and Medical Research Council
Funding Amount
$390,203.00
Summary
A revolutionary new therapy for treatment of growth restricted fetuses and premature babies is being developed through the administration of Colony Stimulating Factor (CSF-1). We have evidence that CSF-1 therapy can promote kidneys and lungs to continue development and maturation after birth. This exciting new finding allows for the application of CSF-1 therapy for both the treatment of premature babies and unborn babies with kidney defects.
Brain Repair Following Stroke: The Role Of Npas4, A Neural-specific Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$611,053.00
Summary
Stroke is the #1 cause of adult disability in Australia and #2 cause of death. About 60,000 Australians suffer a stroke each year while about 250,000 live with the disabilities of stroke, costing over $2B/year. The Queen Elizabeth Hospital and University of Adelaide will study why the Npas4 gene switches on after stroke and the role it plays in brain repair. Future health benefits may be tests to help improve stroke outcome in patients and therapy to decrease loss of brain cells after stroke.
Priming The Maternal Immune Response To Resist Inflammatory Disorders Of Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$920,972.00
Summary
Preeclampsia and preterm birth are common conditions affecting >15 million pregnancies annually. An underlying cause is the mother’s immune response, which can react adversely to the fetus causing an inflammatory reaction. This project seeks to find ways to strengthen the maternal immune system beginning before conception. The work will provide insights upon which to advise intending parents and will inform development of new treatments options to protect susceptible women.