Role Of Snail Family Proteins In Male Fertility And Testicular Cancer
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Male fertility requires production of healthy sperm in the testis. This project builds on our discoveries that testicular cells regulate gene activity via the Snail family of proteins during sperm development, and that interruption of their activities reduces fertility in mice and fruitflies. Snail proteins are also active in cancer cells. We propose to study the precise steps in sperm production affected by Snail proteins and how they affect the progression of testicular cancer.
I am a cell biologist investigating how cells in the developing testis communicate to set the stage for normal sperm production in the adult. My studies address what goes wrong in certain clinical conditions including testicular cancer, and our findings a
Disorders of sexual development are amongst the most common birth defects in humans. These conditions have profound consequences for the physical and psychological health of affected individuals. The incidence of these disorders is on the rise, and this has been linked to our increased exposure to chemicals in the environment that affect how our hormones function. This project will investigate how these chemicals affect hormonal pathways that control early 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.
Male fertility requires sufficient production of healthy sperm in the testis. This project builds on our discovery that testicular cells communicate via the wnt family of proteins during sperm development, and that interruption of their activities reduces fertility in mice. We propose to use mouse models to study the precise steps in sperm production affected by Wnt signalling and how it works.
Nodal Signalling In Male Germ Cell Development: Balancing Fertility And Testicular Cancer Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$536,595.00
Summary
Testicular cancer is the most common type of cancer in men aged 20-40 years, and its incidence has doubled in the last 30 years. It is sometimes fetal and often results in infertility. We have discovered new genes that regulate testicular cell behaviour in the developing fetus, and here test the concept that defects in these genes might disrupt cell behaviour to the point where cancers form during adult life. Outcomes may lead to new ways to diagnose and treat testicular cancers.
Testis To Ovary: Hormonal Control Of Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$803,379.00
Summary
We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide f ....We know very little of the genes that control development of the ovary in female fetuses; most study has focused on the formation of the testis in males. We will use a novel experimental model, a marsupial, where by hormonal treatment of developing males we can switch off testis formation and activate the ovarian pathway. These studies will potentially shed new light on the causes of reproductive diseases including ovarian cancer, as well as clarifying the basic biological processes that guide formation of the ovary.Read moreRead less
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
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.