Women are born with a limited supply of eggs and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. This project aims to shed some light on the mechanisms that control egg supply and reproductive longevity in women by investigating the role of the cell death protein Bid within the ovary.
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.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.
Analysis Of Gene Regulation In Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$524,852.00
Summary
Disorders of Sex Development (DSD) are surprisingly common, however the majority of cases still cannot be explained. Our hypothesis is that a significant proportion of DSD is due to disturbed gene regulation. We will use state of the art methods to analyse the regulation of DSD genes. Our research will improve our knowledge of the regulation of genes that affect DSD and provide a diagnosis for DSD patients for whom the underlying cause is unknown. This in turn will improve clinical management.
Muscle Fusion Defects May Be A Common Cause Of Human Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$391,419.00
Summary
While muscle fusion is a crucial step of muscle formation, it is surprising that human muscle diseases were never associated with muscle fusion defects. We have recently undertaken a genome-wide functional screen using a mouse muscle cell line. We identified 21 genes that were previously associated with muscle dystrophies in human. The aim of this project is to examine the role of those genes during muscle fusion in vivo, using the chick embryo, mouse mutants and lines from patients as models.
Birth defects can have devastating consequences for individuals and their families, and improving our ability to diagnose and screen for these disorders has implications for treatment and reproductive options. We are using the mouse as a model to discover genes important in a new class of birth defects caused by dysfunction of a hair-like cellular projection known as the cilium.
Stress-induced Disease Risk For Pregnant Mothers Born Small
Funder
National Health and Medical Research Council
Funding Amount
$613,124.00
Summary
This proposal addresses the likelihood that mothers born small and exposed to stress during pregnancy will develop adverse physiological adaptations to pregnancy, slowing placental and fetal growth, programming intergenerational disease and compromising maternal health later in life. The outcomes from our human and rat studies will enable development of diagnostic tests to identify pregnancies at greater risk and lead to therapies to reduce adverse intergenerational and long-term health effects.
The Hippo Pathway, Neural Stem Cells And Brain Growth
Funder
National Health and Medical Research Council
Funding Amount
$363,137.00
Summary
During organism development, the brain grows to the right size without overgrowing. Neural stem cells are key regulators of brain size. We will define how the Hippo pathway crosstalks with nutrition-induced signals to control proliferation of neural stem cells and brain size. As well as producing important insights into normal growth, we will increase our understanding of brain diseases associated with aberrant brain growth, such as cancer.
Interaction Between Moz And PRC1 In Defining Epigenetic States And Gene Expression Patterns
Funder
National Health and Medical Research Council
Funding Amount
$427,271.00
Summary
Regulation of gene expression is implicated in all disease processes. Aberrant gene expression is particularly associated with tumour formation. In this project we determine the relationship between an oncogene MOZ and another oncogene BMI1. Together these proteins regulate one of the most important systems controlling gene expression at the level of chromatin structure.