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.
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.
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
21,000 Australians receive kidney replacement therapy and many more die of kidney failure as a result of kidney fibrosis. TGF-?, a growth factor causing kidney fibrosis, is also anti-inflammatory and promotes healing. We aim to prove that targeting downstream messengers (Foxo/?-catenin) of TGF-? will prevent fibrosis while promoting TGF-?’s anti-inflammatory and healing actions. A successful outcome will lead to a novel cure for preventing kidney failure and failure of other organs.
The Role Of TGFB1 In The Pathophysiology Of Late Stage Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$612,961.00
Summary
Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their ....Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their disorder progresses.Read moreRead less
Effect Of Prostaglandin E2 On The Periodontium And Alveolar Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is pl ....Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is placed in contact with mandibular bone, adjacent to erupted teeth, new bone and cementum formation occurs. The ability of PGE2 to induce new bone formation indicates a potential use for PGE2 in the management of bone loss associated with periodontal diseases, and the formation of new bone around dental implants, and around teeth following orthodontic movement. Growth factors are active in healing and have valuable applications in augmenting wound repair. Osseous and dental tissues are rich in growth factors, and these factors are involved with the regulation of bone metabolism as well as tissue repair, thus the action of PGE2 on the periodontium is most likely regulated via these factors. Since regeneration of the periodontium is a fundamental goal of dentistry, any treatment which leads to predictable formation of new connective tissues and their long term stability would be a major clinical advance.Read moreRead less
Transforming Growth Factor Beta As A Causal Factor In Human Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$634,359.00
Summary
Osteoarthritis (OA) is a common painful degenerative disease of the joints, which constitutes a major and growing public health problem, and for which there are no effective therapies. Our exciting recent research in the mouse has found that TGFb over-activity in the bone has a critical causal role in OA pathogenesis. Because TGFb silencing in bone could provide an entirely new way to slow the progression of OA, we propose to investigate this pathway in human OA.
Dr Gilchrist is a reproductive biologist studying factors that regulate the intrinsic quality of unfertilised eggs. He has developed a new form of hormone-free infertility treatment which he will test in a clinical trial over the next 5 years.
Differentiation Of Pro-fibrotic From Anti-inflammatory Effects Of TGF-? In Kidney Fibrosis By Targeting ?-catenin
Funder
National Health and Medical Research Council
Funding Amount
$593,019.00
Summary
More than 2500 Australians commence kidney replacement therapy each year and many more die of kidney failure as a result of kidney fibrosis. TGF-?, a growth factor causing kidney fibrosis, is also anti-inflammatory. Our project aims to prove that targeting a downstream messenger (?-catenin) of TGF-? will prevent kidney fibrosis while leaving TGF-?’s anti-inflammatory actions untouched. A successful outcome will lead to a novel cure for preventing kidney fibrosis and fibrosis of other organs.