New Models For The Onset Of Virilisation In The Developing Male
Funder
National Health and Medical Research Council
Funding Amount
$405,750.00
Summary
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 are hindered because in most mammals virilisation occurs in utero, 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 us ....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 are hindered because in most mammals virilisation occurs in utero, 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, to test hypotheses that explain why different male tissues - such as the reproductive ducts, prostate and penis - start to differentiate at widely different times. We will investigate pathways of androgen formation and the activation and inactivation of hormones in the target organs, and the role of hormone binding proteins. We will also investigate the role of growth factors that may mediate growth of the penis during early development. The results of these experiments will direct funding in subsequent years to test for corresponding gene mutations in our collection of over 200 specimens from patients with defects of virilization (pseudohermaphroditism) 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 pseudohermaphroditism of unknown aetiology in humans.Read moreRead less
Quality Assurance In LDR And HDR Prostate Brachytherapy
Funder
National Health and Medical Research Council
Funding Amount
$221,500.00
Summary
Prostate cancer is one of the most commonly diagnosed cancers in men over 55 years of age. Approximately 30% of all diagnosed cancers in this age group are prostate carcinomas. Low and high dose rate brachytherapy are newly established treatment options for early-stage, low-risk, prostate cancer and are an alternative to curative prostatectomy in most patients. Local control and cure of prostate cancer is greatly influenced by the dose distribution generated by both the treatment techniques. Tre ....Prostate cancer is one of the most commonly diagnosed cancers in men over 55 years of age. Approximately 30% of all diagnosed cancers in this age group are prostate carcinomas. Low and high dose rate brachytherapy are newly established treatment options for early-stage, low-risk, prostate cancer and are an alternative to curative prostatectomy in most patients. Local control and cure of prostate cancer is greatly influenced by the dose distribution generated by both the treatment techniques. Treatment plans must be able to deliver a prescribed dose in the tumour, with adequate margins, while minimising the dose delivered to the surrounding normal tissue and critical organs. It is well recognised that, however skilful the radiation oncologist, an ideal dose distribution according to a treatment plan plan does not guarantee a well delivered dose. Complications such as impotence, severe radiation urethritis and severe rectal bleeding will arise if overdosing of the neuro-vascular bundle, urethra and rectum occurs respectively. This project is based on newly developed instrumentation that will allow continuous, realtime, in vivo, monitoring of the radiation dose levels in the urethra and rectum during brachytherapy treatment of prostate cancer. Such monitoring of the treatment procedure, has been identified as a high priority by the American Brachytherapy Society. The technique will allow extensive in vivo and post treatment studies to be performed by clinicians so as to measure the dose levels currently received and identify the optimum acceptable dose levels for future procedures. The outcomes of this project may well be able to be utilised in other forms of brachytherapy treament (e.g. breast, cervical cancer) and other radiation treatment modailities (e.g. conventional radiotherapy and intensity modulated radiotherapy) to also reduce complications associated with these treatment modalities.Read moreRead less
The Role Of The Mammalian Grainyhead-like Gene Family In Neural Tube Closure
Funder
National Health and Medical Research Council
Funding Amount
$569,541.00
Summary
Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning diff ....Failure of the skin to close over the brain and spinal cord during human development results in the devastating congenital birth defects anencephaly and spina bifida, known collectively as the neural tube defects. These are the second most common congenital birth defects affecting 1:1000 pregnancies. Anencephaly is not compatible with life and affected babies die at birth. In contrast children with spina bifida survive, but suffer from limb paralysis, bowel and bladder dysfunction, learning difficulties and psycho-social disturbances. Our laboratories have identified a family of genes essential for the colsure of the neural tube in mammals. The aim of this proposal is to understand the mechanisms of action with a view to developing new therapeutics that mey be used preventatively in these conditions. We also hope that these studies may facilitate the development of a genetic test to screen couples at risk.Read moreRead less
Defects In Epidermal Morphogenesis In Mammalian Grainyhead-like Gene Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this stud ....The cells of the skin play an essential role in development of the mammalian embryo. They are critical for closure of the brain and spinal cord, for forming a protective barrier against infection and noxious stimuli, for preventing excess fluid loss, for repair of defects and wounds, and for the generation of hair. Our laboratory has identified a family of genes that are critical for all these processes. Loss of individual members of the family has different consequences and the aim of this study is to determine the relationship between the genes to further our understanding of the skin and its functions. These studies have direct and important relevance to human conditions such as the congenital birth defects spina bifida and anencephaly, and infant prematurity where the skin is underdeveloped and lacks barrier function. They also have relevance to wound healing and to conditions in which hair growth is affected, such as alopecia. We believe that therapeutic interventions and prenatal diagnostic tests could evolve from these studies.Read moreRead less