The Role Of Non-coding RNAs In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
We have discovered a new mechanism by which genome activity is regulated. This project will test the hypothesis that this mechanism is critical for cell growth and embryonic development. It has the potential to identify new causes of birth defects and may also be relevant to understanding the etiology of other diseases such as cancer, resulting in improvements in diagnosis and management of disorders that present a major health care burden.
Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian c ....Disorders of sexual development are among the most common form of birth defects in humans (1 in 4,000 births) because failure of the gonads to develop does not affect the viability of the individual. Such disorders can have profound psychological and medical consequences upon the individual, family, and society. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutation. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. An understanding of the way gene expression and hence tissue differentiation is altered after sex reversal will inform us about the causes and consequences of normal and abnormal sexual development, gonadal malignancies and infertility. The gonad is unusual in that two completely different organs can arise from an essentially identical primordium, so that errors in development lead to intersexual phenotypes. We will use our new experimental animal model to clarify these processes.Read moreRead less
Hypospadias is one of the most common developmental defects in humans, yet over two thirds of the cases cannot be explained. Our recent studies using marsupials show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that will inform our understanding of this common developmental defect of male development
MicroRNA Regulation Of Sex Determination And Gonad Development.
Funder
National Health and Medical Research Council
Funding Amount
$518,076.00
Summary
Sex determination, the decision to develop into either boy or girl, influences most aspects of our lives. Consequently, disorders of sexual development (~1% of births), resulting in genital abnormalities, infertility and often cancer, are extremely traumatic for the individual. The molecular basis of these disorders is not well understood. This project will identify new factors important for sex determination and therefore will improve diagnosis and clinical care for the patients.
Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar ....Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar wallabies and rabbits, to test 3 hypotheses about 5-alpha-androstanediol and specific enzymes in the developing reproductive tissues that either convert this hormone to active and inactive forms. The results of these experiments will direct testing for corresponding gene mutations in our collection of over 200 specimens from patients with defects of virilisation (pseudohemaphroditism) whose causes are still unknown. It is our expectation that the findings in these studies will provide insight not only into the pathways by which testicular hormones masculinize the developing male, but will also explain instances of male pseudohemaphroditism of unknown aetiology in humans.Read moreRead less
The Second Australian Study Of Health And Relationships
Funder
National Health and Medical Research Council
Funding Amount
$1,637,477.00
Summary
The present proposal is for the Second Australian Study of Health and Relationships, a survey of 20,000 Australians aged 16–69, in 2011–12 in order to understand and document the changes in Australian sexual behaviour over the past decade. It is essential that policy and practice in the arena of sexual and reproductive health be evidence-based and that the evidence base be as current as is practicable.
Identification And Analysis Of Novel Genes And Regulatory Regions Associated With Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Children born with a disorder of sex development (DSD) may differ from typical males or females in their chromosomes, hormones or reproductive organs, sometimes resulting in infertility or gonadal cancer. DSDs are the most common birth defect and yet, most cases are unexplained genetically. I hope to identify new genes needed for gonad formation that cause DSD when mutated. This work will provide answers as to how DSDs arise, and allow informed decision-making regarding possible treatments.