Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
We discovered, characterised and commercialised Macrophage inhibitory cytokine-1 (MIC-1/GDF15) for human therapy. Its blood level predicts death from cancer, heart attack/stroke and other diseases. This study will add important information for understandg the actions of this important protein
Cancer Anorexia/cachexia: Mechanisms For Anorexia And Appetite Regulation By Tumour Derived MIC-1/GDF15
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have recently discovered that MIC-1 is a new appetite suppressive agent which when overproduced in some diseases like cancer, causes severe weight loss. This project sets out to determine the mechanisms it employs in regulation of appetite centres in the brain.
RZR-alpha In The Control Of Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,706.00
Summary
Four million Australians have cardiovascular disease accounting for 35% of all deaths. CVD is the most expensive disease burden and a National Health Priority. Smooth muscle cell growth is a cause of CVD. However, the mechanisms controlling SMC hyperplasia are poorly understood. This project will provide key insights on the role of RZR-alpha in the pathogenesis of blood vessel disease, and develop novel gene-targeting approaches for new opportunities to control complications of CVD.
Therapeutic Potential Of Transforming Growth Factor-beta Proteins For The Diagnosis And Treatment Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$942,961.00
Summary
We discovered and manufactured a growth factor produced uniquely by the egg. We named this growth factor cumulin. It is a powerful regulator of ovarian function and egg quality. This project will study the basic mechanisms of how cumulin works in the ovary. We will then develop an assay to measure it as a biomarker of human egg quality and quantity. New approaches in fertility preservation for cancer survivors will be developed using cumulin.
Mapping The TNF Pathway: A Qualitative And Quantative Molecular Analysis Of The Components And Post-translational Modifications Involved In Physiological And Pathological TNFR1 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$636,258.00
Summary
TNF is a master regulator of the inflammation response and dysregulated TNF signalling causes many human diseases. We will use a cutting edge mass spectrometry technique that we have developed to analyse molecules required for TNF signalling. Understanding how the TNF signalling works in all cell types and with different forms of ligands will open up therapeutic opportunities to selectively target TNF signalling in inflammatory diseases, such as Rheumatoid Arthritis and Cancer.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
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.
We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
Novel Transcription Factor Regulation Of Lymphatic Vascular Angiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,568.00
Summary
Lymphatic vessels control tissue fluid drainage, inflammatory processes and cancer progression. We have used genetic approaches to discover an unexpected role for a family of factors (transcription factors) that regulate new lymphatic vessel formation. This project will investigate this biological function of these genes in detail in vascular formation. The project aims to generate important knowledge for vascular biology, vascular pathologies, cancer spread and future therapeutics.