Homeodomain Nkx2-5-dependent Negative Feedback Loop Important In Heart Development And Congenital Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,330,245.00
Summary
Congenital heart disease (CHD) is the cause of most deaths in children in the first year of life. We have identified a genetic pathway important for both normal cardiac development and CHD that involves the cardiac transcription factor Nkx2-5. This pathway controls a transition in embryos between cardiac cell specification and expansion. We will now explore the biochemical and genetic mechanisms underlying this pathway to help us understand CHD and identify its causative genes.
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.
Identifying The Critical Pathways Which Regulate Vertebrate Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$552,131.00
Summary
Understanding the genes which underlie human birth defects is of immense clinical importance. Our laboratory is a world-leader investigating a gene responsible for facial skeleton development, Grhl2. With our wide range of models, we will discover how Grhl2 works to ensure the face and skull develop properly during birth.
Genetic Autopsy Of Perinatal Death: Diagnosis And Discovery By Genome Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$989,332.00
Summary
Stillbirth, miscarriage and genetic termination of pregnancy are common and traumatic events. Despite medical investigation, many of the causes of these events are unexplained. This project plans to employ the latest in whole genome sequencing and functional modelling to explain these occurrences as well as lead to an increase in knowledge of genetics and development.
Novel Roles For Neural Crest Cells In Cardiac Morphogenesis
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Abnormal formation of the cardiac outflow tract leads to common malformations affecting over 1% of all births. Taking advantage of novel mouse models this grant aims to identify the molecular mechanisms by which neural crest cells control formation of the cardiac outflow tract. New information generated from this study stands to identify new targets which may be used for predictive testing and regenerative therapies.
Identifying The Genetic And Environmental Causes Of Congenital Malformation
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Birth defects are common, devastating and costly to families and to society. The cause is unknown in 80% of cases. This research is helping families by finding the gene mutations that cause birth defects. Gene discoveries, in some cases, will highlight environmental factors that are important for normal embryo formation, such as oxygen levels and dietary components. By identifying gene and environmental factors associated with causing birth defects, we hope to ameliorate or prevent many cases.
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.
A Novel Gene Family Implicated In Neural Crest And Craniofacial Malformation
Funder
National Health and Medical Research Council
Funding Amount
$695,016.00
Summary
We have identified a new type of receptor that when defective causes facial clefting in animal models. We are using our unique laboratory and clinical resources to understand how these birth defects occur and to investigate the molecular signalling events that are controlled by this olfactory receptor. These studies will pave the way to designing pharmaceuticals that may eventually ameliorate or even stop this major group of birth defects.