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.
Katanin P80 Is A Key Regulator Of Microtubule Dynamics And Male Fertility.
Funder
National Health and Medical Research Council
Funding Amount
$603,756.00
Summary
Male fertility is a complex process requiring the co-ordinated activation of thousands of gene products. It is not surprising therefore that 1 in 15 Australian men are infertile. This project will explore an essential pathways for sperm production, specifically related to sperm shaping and motility. This work may ultimately have implications for the diagnosis and treatment of male infertility, but also for pathology in tissues will similar cellular structures.
Postnatal Germ Cells Are Controlled By FSH During 'minipuberty' At 3-6 Months, And Deranged By Cryptorchidism To Cause Seminoma And Infertility
Funder
National Health and Medical Research Council
Funding Amount
$813,739.00
Summary
This study will investigate the exciting possibility that the risk of cancer and infertility in adulthood in infants born with undescended testes might be obviated by understanding how primitive sperm cells behave in the postnatal testis. The study will define the key changes to the primitive sperm cells, including their timing and control by hormones, so surgery is done at the right time +/-accessory hormone treatment to optimise future sperm function for babies with undescended testes.
Determining The Impact Of Inherited Epigenetic Information On Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,691.00
Summary
Recent observations show that the environment in which you live can alter disease susceptibility in your children, without altering the sequence of your genes. This is due to epigenetic mechanisms which control the way the DNA is interpreted. In this study we will study the potential for epigenetic mechanisms to affect sperm production and impact characteristics and disease in the next generation.
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).
Epigenetic Regulation Of Male Fetal Germ Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$562,176.00
Summary
Men’s health has declined over recent decades, but the causes remain unknown. Non-genetic (epigenetic) mechanisms affecting formation and function of the male germ cells (which produce sperm) may play an important role. We will determine the role of a key epigenetic modifier on the formation and function of male germ cells, including germ cell tumours. This study will provide fundamental insights into male germ cell epigenetics, and significantly contribute to understanding men's health.
Role Of The Histone Variant H3.3 In Germ Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$581,223.00
Summary
Over their life cycle, germ cells are unique in undergoing a large scale reformatting of their gene or DNA control systems, required for their own development, and for the development of the fertilized egg. We think that the protein ïhistone H3.3Í is crucial to this reformatting process. We will test this possibility by determining how much H3.3 is present in germ cells. Also, we will make mice which lack this protein in germ cells to see if this affects the reformatting process.
Molecular Regulation Of Pluripotency In The Mammalian Germline
Funder
National Health and Medical Research Council
Funding Amount
$611,935.00
Summary
Germ cells generate sperm in males or oocytes in females. In males, germ cell numbers are tightly controlled in the embryo, with too few germ cells causing infertility, and unrestrained germ cell numbers leading to testicular cancer. We have discovered a molecular mechanism that regulates germ cells in the embryo, and propose to study in mice how this regulation is accomplished and the consequences of defective regulation, in order to learn more about how infertility and testis cancer arise.
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.
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.