I am a developmental biologist who identifies and characterises genes required for normal embryonic development in mouse. I translate this information into the genetic diagnosis and developmental understanding of congenital malformations in humans.
Improving Respiratory Transition And Outcomes Of Newborn Infants
Funder
National Health and Medical Research Council
Funding Amount
$262,251.00
Summary
Effective mask ventilation is the most important intervention at birth that can reduce mortality and disability in term and preterm infants. I will develop strategies to help clinicians improve their resuscitation skills. I will also study new ways to better support babies’ transition after birth, to improve their short and long term outcomes. The results of this research will change the way newly born babies are cared for around the world.
Functional Screening Of Novel Genes In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Our faces are central to our ability to communicate, feed, breath and interact with each other. Birth defects that impact on the normal development of the face are common and affect not only the child but have a dramatic impact on the child's family as well. The genetic causes of most facial birth defects are unknown. This project will develop a method for determining how development of the face is controlled and will help identify genes that are responsible for facial birth defects.
Defining The Genetic Causes Of The Abnormal Vertebral Segmentation Syndrome, Spondylocostal Dysostosis
Funder
National Health and Medical Research Council
Funding Amount
$476,523.00
Summary
There are many birth defects that cause vertebral malformations along the spinal column. These occur as the embryo develops in utero, during the formation of structures known as somites. Somites also form the ribs, muscle, tendons and dermis. We are studying an example of this type of birth defect called spondylocostal dysostosis (SCD). We have shown that mutations in three different genes cause some cases of this inherited disease in humans. These genes are called DLL3, MESP2 and LFNG. However, ....There are many birth defects that cause vertebral malformations along the spinal column. These occur as the embryo develops in utero, during the formation of structures known as somites. Somites also form the ribs, muscle, tendons and dermis. We are studying an example of this type of birth defect called spondylocostal dysostosis (SCD). We have shown that mutations in three different genes cause some cases of this inherited disease in humans. These genes are called DLL3, MESP2 and LFNG. However, 80% of SCD patients do not have a mutation in any of these genes. Thus we need to discover how these other cases occur. This project uses two strategies in parallel. Firstly, we will analyse large families that have a history of SCD, and use this information to find causative gene mutations. However, a significant proportion of cases occur without family history. To find out what genes are involved in these cases is more difficult. We have created a mutant mouse by specifically deleting the DLL3 gene. This mouse has very similar vertebral malformations to SCD. We will compare embryos from normal and mutant mice to find genes that do not operate normally in the mutant. These genes are candidates for causing SCD, and thus we will screen these genes in human patients for mutations. However, simply finding a change in a candidate gene does not necessarily mean that this is the cause of SCD. To prove this, we have developed several tests to determine if the mutation alters the normal function of the protein encoded by the mutated gene. This work will greatly benefit the future genetic assessment of SCD patients. In addition, by studying our mouse model of SCD, we will gain a greater understanding of how DLL3 functions. This knowledge may be useful in developing stem cell-based therapies that involve the production of specific cell types.Read moreRead less
I am an epidemiologist using record linkage to investigate the causes and consequences of developmental disabilities such as birth defects, intellectual disability and autism and to identify possibilities for their prevention and amelioration.
Risk Of Birth Defects In Children Born Following Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$191,962.00
Summary
The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand bir ....The development of assisted reproductive technology (ART) for infertility treatment has advanced at a tremendous pace since late 1970's. The use of ART is becoming increasingly frequent, with Australia having one of the highest rates of use internationally. Over 4,000 births result from ART annually in Australia. At the same time, minimally invasive infertility treatment-ovulation induction and insemination, remains a main option for some infertile couples and also generates several thousand births annually. A fundamental concern for those involved in infertility treatment is the health of the children born following the treatment. Evidence from many studies indicates that compared to the general population, ART babies are more likely to be a twin or triplet, have a low birth weight, be born premature, and suffer higher rates of perinatal death and cerebral palsy. These issues are gradually being addressed by transferring a single embryo in a cycle. Of greater concern is the recent reporting by a Western Australian team that the risk of major birth defects is doubled in ART children. This is a highly significant finding that has raised concern in patients and clinicians. It is imperative to verify the findings through replication in a larger study. It is equally important to identify whether the increased risk is due to potentially modifiable treatment factors or patient factors related to their infertility. This innovative study will therefore also separate patient characteristics and type of treatment, and partition the risk attributable to various factors. The health of children from infertility treatments is of fundamental concern and has become an important public health issue. This study will direct future basic research in embryology and clinical services where there is a continual need to balance technical innovation and efficacy with treatment safety. The long-term benefit will be improvement of the health status of Australian families.Read moreRead less
Metabolic And Molecular Determinants Of Embryo Viability
Funder
National Health and Medical Research Council
Funding Amount
$551,321.00
Summary
We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data dem ....We know that our health as adults is influenced by the lifestyle of our mothers during pregnancy. In particular, increased risk of adult-onset diseases such as diabetes and cardiovascular disease occurs when small and lean infants at birth are raised in conditions where nutrient intake is not restricted and obesity occurs. This concept of fetal programming is now widely accepted. Our laboratory is leading research in a new concept, that of embryonic programming. We have extensive animal data demonstrating that exposure of embryos to physiological perturbations alters fetal development, similarly to that occurring in nutrient restriction during pregnancy. Furthermore, there is data from IVF-derived children that their birth-weight is lower than expected, possibly due to the conditions used for conception in the laboratory. How does the response by eggs and embryos, at the time of conception, affect subsequent development? There has been some focus on changes to DNA that are not related to mutations, but structural changes in the DNA that alters gene expression. We call this epigenetics and epigenetic changes are found in embryos, including human embryos following IVF. However, no one knows how such epigenetic changes occur as a result of this stress response by the egg or embryo. Our proposal is to determine the mechanism of how epigenetic alterations take place in eggs and embryos. Our theory is that the mitochondria, the energy producing packages within all cells, are sending signals to the embryo's nucleus. When the egg or embryo finds itself in adverse conditions, the signals change as a result of changes in the energy balance. This in turn changes the activity of enzymes in the nucleus that regulates DNA structure. If we can prove that this relationship occurs, then we can assess these changes in human embryos that are excess to a patient's requirements and learn if programming takes place in human embryos.Read moreRead less