The Role Of The Mammalian Grainyhead-like Gene Family In Neural Tube Closure
Funder
National Health and Medical Research Council
Funding Amount
$635,547.00
Summary
Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Our laboratories have identified a family of genes essential for the closure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action of these genes with a v ....Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Our laboratories have identified a family of genes essential for the closure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action of these genes with a view to developing new preventative therapeutics.Read moreRead less
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.
Generation Of Renal Cells From Human Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$281,805.00
Summary
This proposal will gather evidence to show that human embryonic stem cells are capable of forming specific cell types of the embryonic human kidney. Once this is established, methods for the maintenance and directed differentiation of these cells to cell types of the mature kidney will be identified and improved. The results obtained will provide a base for future exploration of the possibility that human embryonic stem cell derived cells can be used to treat damaged kidneys.
Multipotent Stem Cells Derived From Postimplantation Mouse Embryos: Evaluation Of Germ Layer Differentiation Potential
Funder
National Health and Medical Research Council
Funding Amount
$788,818.00
Summary
This study of the properties of cells that can differentiate into specific lineages provides useful insights into the cellular and molecular mechanisms for the specification of these progenitors from the pluripotent stem cells. The procurement of tissue-specific precursor cells that are capable of self-renewing and population expansion is a critical pre-requisite for achieving directed differentiation of stem cells into therapeutically useful cells for tissue replacement and regeneration.
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.
Defining The Role Of IGF-1 As A Novel Angiocrine Factor In The Development And Treament Of Common Craniofacial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$573,848.00
Summary
1 in 1000 children are born with a small jaw, which requires invasive surgery for treatment. We identified that defects in blood vessel development in the jaw underlie some cases of these craniofacial defects. We found that factors secreted from the major artery in the jaw can promote jaw growth, and our research proposal aims to identify what exactly these factors are. These factors have the potential to be used to therapeutically treat children with a small jaw to help it grow correctly.
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.
Modulation Of Telomere Length And Subtelomeric DNA Methylation In Response To Oxidative Stress In The Male Germ Line; Implications For Tumorigenesis In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$310,684.00
Summary
This research project is designed to elucidate how the quality of a father’s spermatozoa can impact upon the health and wellbeing of his children. We hypothesize that factors, such as infertility, heavy smoking or age create a state of oxidative stress in the testes and that this stress influences the genetic structure of spermatozoa in such a way that the incidence of spontaneous mutations and susceptibility-to-cancer are significantly elevated in the offspring.
Investigating The Formation And Utility Of The Prenatal Platelet Forming System
Funder
National Health and Medical Research Council
Funding Amount
$793,442.00
Summary
A major challenge to regenerative medicine is discovering how to produce useful cell types in the laboratory. Particularly urgent is the need to generate large numbers of platelets, the building blocks of the clotting system, for clinical use. Current laboratory methods are woefully inefficient, thus cannot meet demand. This project aims to discover how platelets are made in nature. With this information we will be able to devise better platelet production strategies in the laboratory.