The Embryological And Molecular Basis Of Zic2 Involvement In Holoprosencephaly
Funder
National Health and Medical Research Council
Funding Amount
$624,145.00
Summary
The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language ....The brain is the most complex organ in the human body and diseases or disorders of the brain can become evident at any stage of life. Generally such problems have profound consequnces for the affected individuals and their families. One of the most common problems of brain development that is evident either at birth or within the first years of life is called holoprosencephaly (HPE). This condition affects the midline of the brain and the face and can lead to delay in mental, motor and language development, seizures, and obvious facial abnormalities. In its most severe form only one eye develops in the middle of the face, a condition known as cyclopia and a large majority of the severely affected children will die late in gestation or at birth. This condition can be inherited, but because the genetic lesions that cause this problem affect different people differently, people can carry the causative genetic change(s) without knowing it. We need to identify and study the genetic lesions that contribute to this condition in order to begin to understand how we can stop these mutations affecting the developing foetus. Because it is difficult to study embryonic development in humans we have generated a mouse model of this condition. In the mouse model just one gene (called Zic2) is altered and embryos that have two copies of this alteration develop the most severe form of cyclopia and die in the second half of gestation. This means that the normal role of this gene is to stop us developing HPE. We will use this mouse model to see just when and how the Zic2 gene prevents HPE. In addition, we will look to see what other genes Zic2 interacts with by breeding mice that carry the mutation in Zic2 with mice that carry a mutation in a second gene that can also cause HPE. These experiments are very important because if we understand how Zic2 and other genes protect us from HPE we can begin to design strategies to decrease the risk of a child developing this condition.Read moreRead less
Cellular And Molecular Regulation Of Fetal Ovarian Development
Funder
National Health and Medical Research Council
Funding Amount
$547,315.00
Summary
Normal development of the ovaries is critical for women's health and reproduction. Recent studies have shown that even the very earliest steps in ovarian development, occurring during fetal growth, can play a major part in predisposing to some of the most common and debilitating reproductive and endocrine disorders affecting Australian women. In this project we will take a systematic and comprehensive approach to exploring the mysteries of fetal ovary development, discovering what genes need to ....Normal development of the ovaries is critical for women's health and reproduction. Recent studies have shown that even the very earliest steps in ovarian development, occurring during fetal growth, can play a major part in predisposing to some of the most common and debilitating reproductive and endocrine disorders affecting Australian women. In this project we will take a systematic and comprehensive approach to exploring the mysteries of fetal ovary development, discovering what genes need to be activated and what cellular processes are required for normal ovary development and hence may play a part in ovarian diseases that manifest in later life. This work will offer new avenues for the prevention, diagnosis and treatment of ovarian disease and female infertility.Read moreRead less
Does Mobile DNA Activity Contribute To Reproductive Failure?
Funder
National Health and Medical Research Council
Funding Amount
$389,076.00
Summary
One in four pregnancies in Australia will end in miscarriage. Infertility affects about 15% of Australian couples and is highly correlated with increasing maternal age. In this study, we will use cutting edge single-cell genomic approaches to investigate the activity of mobile DNA elements or “jumping genes” as a previously unexplored cause of reproductive failure, including spontaneous miscarriage and age-related female infertility.