Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.Read moreRead less
Understanding The Contribution Of SRNAs To Antibiotic Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$587,424.00
Summary
Golden Staph is a major problem in Australian hospitals. This project will use cutting edge technology to investigate how Golden Staph responds to and resists antibiotics used to treat human infections, leading to new strategies for the prevention and treatment of antibiotic resistant bacteria.
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.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Transcriptional Effectors Of Oncogenic ERK Signaling In Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$820,776.00
Summary
This project aims to unravel how one of the most frequently deregulated molecular pathways in colorectal cancer controls the expression of genes required for these tumours to grow and spread. We expect this work to uncover novel therapeutic targets to effectively inactivate this pathway and biomarkers to select patients most likely to benefit from existing therapies.
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
Molecular Basis For Stress-induced Gene Regulation—a Model System To Understand Transcriptional Deregulation In Cancer And Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Deregulated gene transcription plays a critical role in cancer formation. It is therefore important to understand the molecular basis of gene transcription and how tumour cells hijack the process. In this Project, we will study the molecular basis of stress-inducible gene expression. This is particularly important for understanding the molecular basis of cancer as stress-inducible genes are activated by transcription factors implicated in breast, colon, lung, and prostate cancers.
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.