Exposing The Mechanisms Underlying Mammalian Meiotic Onset
Funder
National Health and Medical Research Council
Funding Amount
$536,563.00
Summary
Germ cells must undergo a special form of cell division, meiosis, before they can form oocytes in females or sperm in males. We want to know, in detail, how meiosis is triggered in germ cells and what the first steps are in meiotic progression. This information will help us understand the causative factors in infertility (1 in 6 couples of reproductive age are infertile), control fertility (develop new contraceptives) and avoid testicular cancer (the most common tumour type in young men).
Whether we are born as a male or a female affects our sense of social place, behaviour, gender identity, reproductive options, and disease susceptibility. I am a molecular geneticist investigating the biology of gender. I study the mechanisms underpinning sexual development, with an emphasis on identifying the genetic causes of ‘intersex’ and transsex disorders. I am also studying how SRY, a male gene, controls voluntary movement, and its possible link to Parkinson’s disease.
Characterisation Of Conserved Sox18-dependent Genes In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$401,355.00
Summary
Lymphatic vessels are important in a number of diseases including lymphoedema and cancer. There is a significant gap in our basic understanding of how lymphatic vessels form. We have identified a series of genes that are regulated downstream of the lymphatic master gene Sox18 in mouse lymphatic vessels. This study aims to characterise these genes using complementary model systems. The genes and pathways identified will represent potential therapeutic targets in a number of disease contexts.
Transcriptional Control Of Blood Vessel Development By Sox18
Funder
National Health and Medical Research Council
Funding Amount
$468,564.00
Summary
Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of ....Blood vessels play an essential role in maintaining the supply of nutrients to every organ and tissue in the body. Improper development of blood vessels in the embryo can compromise survival of the embryo, and defects in the ability of blood vessels to grow, regenerate and adapt to change during adult life can be life-threatening. The growth of new blood vessels (angiogenesis) is also an important factor in the ability of solid tumours to grow during the progression of cancer. It is therefore of fundamental importance in the health sciences to gain an understanding of how blood vessels form and regenerate. As a result of our collaborative research efforts, we have discovered a gene, Sox18, that appears to regulate blood vessel development by controlling the formation and-or behaviour of endothelial cells, which line the blood vessels and make them impermeable. Our research so far indicates that MICE WITH DEFECTS IN SOX18 DIE FROM VASCULAR DEFECTS, underlining the importance of this gene. THIS PROJECT IS CONCERNED WITH FINDING OUT HOW SOX18 WORKS - exactly what goes wrong in mice lacking this gene, whether Sox18 can influence endothelial cell behaviour in cell culture, how Sox18 comes to be active in endothelial cells, what genes are switched on by Sox18, and what genes Sox18 co-operates with in its role in endothelial cells. The answers to these questions will not only provide fundamental basic information about how blood vessels development is controlled, but also sow the seeds for possible future therapies in which blood vessel development could be stimulated (eg in wound healing) or suppressed (eg in tumour progression) through pharmaceutical intervention.Read moreRead less
The Role Of Sox8 In Sex Determination And Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
We have discovered a new gene called Sox8. This gene is very closely related to another gene, Sox9, that is known to be a critical factor in determining whether an embryo develops as a male or female by specifying whether the embryo makes testes or ovaries. We have found that Sox8, like Sox9, is active in the cell type in fetal testes known to be important for the development of maleness, at around the time when the male-female decision is being made. We therefore believe that Sox8 is an importa ....We have discovered a new gene called Sox8. This gene is very closely related to another gene, Sox9, that is known to be a critical factor in determining whether an embryo develops as a male or female by specifying whether the embryo makes testes or ovaries. We have found that Sox8, like Sox9, is active in the cell type in fetal testes known to be important for the development of maleness, at around the time when the male-female decision is being made. We therefore believe that Sox8 is an important part of the genetic chain of events leading to normal male development. We aim to study how Sox8 exerts its effects on male development. We have also found that in humans, Sox8 is located in a chromosomal region associated with a developmental disease syndrome characterized by mental retardation, facial defects and anomalies of male sexual development. Sox8 is active in mouse embryos in all the tissues affected by the human disease. We believe defects in SOX8 in humans are largely responsible for this disease, called ATR-16 syndrome. We will test whether patients with ATR-16 have defects involving SOX8 in their DNA in order to test this theory. In summary, we believe we have found a new human disease gene which will further our understanding of how developmental diseases arise in the embryo. In addition, this work will shed light on the process of sexual development, a significant healthcare problem in view of the fact that defects in sexual development are among the most common forms of birth defects.Read moreRead less
The Role Of SOX14 In Limb Development And Human Limb Defects.
Funder
National Health and Medical Research Council
Funding Amount
$257,606.00
Summary
Little is known about the mechanisms that control limb development. We have discovered a new gene which is active in the developing limb of the embryo. This study will provide information on how this new gene controls the development of the limb. Limb defects occur in 1 in 1,000 new-born babies. We believe the absence of our newly discovered gene may be responsible for some of these limb defects. Ultimately, this fundamental knowledge may lead to improved pre-natal diagnosis and better treament ....Little is known about the mechanisms that control limb development. We have discovered a new gene which is active in the developing limb of the embryo. This study will provide information on how this new gene controls the development of the limb. Limb defects occur in 1 in 1,000 new-born babies. We believe the absence of our newly discovered gene may be responsible for some of these limb defects. Ultimately, this fundamental knowledge may lead to improved pre-natal diagnosis and better treament for limb abnormalities.Read moreRead less
Functional Characterisation Of Long Spliced NcRNAs
Funder
National Health and Medical Research Council
Funding Amount
$649,230.00
Summary
Genome sequencing projects suggest we only have approximately thirty thousand coding genes which was previously considered to be far too few to provide the blueprint for generation of human complexity. More surprising was the discovery that 3-5% of the genome is transcribed but not translated into protein. The function of these non-coding RNAs is unknown but hotly debated. Is it junk? Or does it play a new key role in programming development? This grant will address this question directly.