Cell Cycle Regulation By The Epidermal Growth Factor Receptor
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The rate of growth and death of normal cells is regulated through signals transmitted from the cell surface to the nucleus. In many human cancers the normal regulatory mechanisms are subverted, leading to uncontrolled growth of the cells. We aim to characterize the signals that are initiated by binding of the Epidermal Growth Factor (EGF) to its receptor and to understand how these signals influence the ability of the cell to divide and to survive. We will identify the pathways that contribute t ....The rate of growth and death of normal cells is regulated through signals transmitted from the cell surface to the nucleus. In many human cancers the normal regulatory mechanisms are subverted, leading to uncontrolled growth of the cells. We aim to characterize the signals that are initiated by binding of the Epidermal Growth Factor (EGF) to its receptor and to understand how these signals influence the ability of the cell to divide and to survive. We will identify the pathways that contribute to uncontrolled growth in tumor cells. This knowledge is necessary for the design of new therapies targetted to the molecular lesions which stimulate solid tumors.Read moreRead less
This project aims to study the hormonal control of Sertoli cell development and function. In the testis, these highly specialised cells provide essential nutritional and structural support for sperm production. In current NHMRC-supported research we created a unique mouse model to study the individual roles of two key reproductive hormones FSH and testosterone in spermatogenesis. This novel approach involved the selective expression of transgenic FSH on the hormone-deficient background of hpg mi ....This project aims to study the hormonal control of Sertoli cell development and function. In the testis, these highly specialised cells provide essential nutritional and structural support for sperm production. In current NHMRC-supported research we created a unique mouse model to study the individual roles of two key reproductive hormones FSH and testosterone in spermatogenesis. This novel approach involved the selective expression of transgenic FSH on the hormone-deficient background of hpg mice, which normally lack both androgens and FSH. Our analysis revealed that FSH provided the main stimulation for Sertoli cell and early germ cell proliferation, whereas FSH required testosterone for later stages of sperm formation. In this proposal we now plan to investigate FSH and the changing steroidal contributions during the critical postnatal stage of Sertoli cell development. We will study individual of combined actions of FSH and steroids, including the controversial role of estradiol in Sertoli and germ cell function, which may all have profound consequences on sperm production and male fertility. We will also establish unique mouse models to address fundamental questions about the mechanisms of androgen actions in the testis, and the requirement for androgen receptor expression in Sertoli and neighbouring peritubular cells for the overall testosterone response. Furthermore, we will use new microarray gene screening technology to identify the FSH- and androgen-regulated gene pathways during Sertoli cell proliferation. This research has relevance to the controversial view of environmental steroids affecting human testicular development and reducing sperm counts, and offers the potential to uncover new causes of previously unexplained male infertility or testicular cancers, and to help develop better strategies for hormonal male contraceptives, and treatments for male infertitliy or cancer.Read moreRead less
This research program entitled Stem cells from the testis is designed to use cutting edge molecular and cellular biology techniques to isolate adult stem cells from the testis. These stem cells will be expanded in cell culture and tested for therapeutic activity in mouse models of infertility, leukaemia and kidney failure. The knowledge and techniques developed in the mouse system may help unlock the potential of human cell based therapies for these and other degenerative diseases.
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Prof Alan Connelly is an internationally recognised neuroimaging researcher specialising in MRI. His major areas of research are in the development of new methods to acquire and process MR images of both structural and functional aspects of the brain, and the application of these novel methods to clinical neuroscience problems. His work has had a major impact in the field of epilepsy, where techniques that he pioneered have been widely adopted in specialist epilepsy centres worldwide.
Mild traumatic brain injury (TBI) is a leading cause of death and disability in Australia, especially in young populations. Although many patients recover uneventfully following mild TBI, complications such as prolonged symptoms, depression and cognitive deterioration may occur. With considerable advancements in neuroimaging and cognitive assessment in recent years, newer techniques may provide a window to directly observe changes that accompany mild TBI.
Development of normal brain function requires information transfer and integration from outside and within the brain. Normal brain wiring is guided by genetic and environmental cues, whose relative contributions remain controversial. This project investigates the physiological and behavioural consequences of abnormal brain wiring, and the potential for controlled environments and targeted interventions to overcome the deficits. Relevance includes neurotrauma as well as mental illnesses.