The ZIC3 Heterotaxy-associated Transcription Factor: A New Player In Nuclear Control Of Canonical Wnt Signalling
Funder
National Health and Medical Research Council
Funding Amount
$992,822.00
Summary
Humans have many internal asymmetries that need to occur in a consistent manner across all individuals. Examples of asymmetry include our unpaired organs (like the heart or liver) or a paired organ with asymmetry (like the lungs). In this project we will use cutting edge molecular embryology and cell biology techniques to explore the mechanisms behind the remarkable feat of establishing asymmetry so we are better able to help those individuals with laterality disorders.
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
Compound Culture Media To Improve Human IVF Pregnancies
Funder
National Health and Medical Research Council
Funding Amount
$254,340.00
Summary
In Australia 1 in 6 couples require IVF to conceive. Although pregnancy rates have improved over the last 10 years the live birth rate in Australia per cycle is only 17%. This project will assess a new method for the culture of embryos for the ability to maintain embryo vitality and produce healthy babies.
Reappraisal Of The Mechanisms Underlying Implantation Success Or Failure
Funder
National Health and Medical Research Council
Funding Amount
$750,755.00
Summary
Infertility affects 1:6 Australian couples; these seek help. However, for each IVF cycle, there is only ~18.5% chance of a live birth, significantly due to failure of embryo implantation. We discovered nano-vesicles in the uterine cavity, that are released from the womb lining and taken up by the pre-implantation embryo to improve its implantation potential. We will determine how this extracellular environment can enhance implantation success and circumvent/management of infertility.
Genetic testing of IVF embryos promises to improve success but shows no effect of live-birth rates. Many embryos are mosaic: containing cells with correct and incorrect chromosome numbers. Current testing is an invasive biopsy which fails to diagnose how many cells are abnormal in the cells that develop into the baby. Here we will use imaging to determine the ratio of abnormal:normal cells resulting in a non-invasive diagnostic that will improve IVF success.