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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.
A Role For Epigenetic Modifiers In Maintaining Chromosome Integrity During Passage Through The Male Gamete In The Mouse.
Funder
National Health and Medical Research Council
Funding Amount
$390,541.00
Summary
There is a high level of infertility in the human population, the majority of which remains unexplained. 15% of married couples in the United States are affected by infertility and it is estimated that the male partner is responsible for half of this. Some of this infertility is familial indicating an underlying genetic cause. An increased understanding of the underlying genes involved, should lead to improvements in treatment. The mouse, with its ability to produce large numbers of offspring an ....There is a high level of infertility in the human population, the majority of which remains unexplained. 15% of married couples in the United States are affected by infertility and it is estimated that the male partner is responsible for half of this. Some of this infertility is familial indicating an underlying genetic cause. An increased understanding of the underlying genes involved, should lead to improvements in treatment. The mouse, with its ability to produce large numbers of offspring and its ability to be genetically modified, provides an excellent model system for studying the genetic contribution to reproductive fitness. The studies outlined in this application aim to determine whether a group of genes, previously identified as a result of their effects on epigenetic gene silencing, are also involved in reproductive fitness in the mouse. Our hypothesis is that these genes encode proteins required for normal pairing and segregation of chromosomes during male gametogenesis. While none of the experiments described here involve studies on humans, the genes identified are likely to have human homologues. It will, then, be relatively simple to discover whether infertile men carry mutations in these genes. Assisted reproductive technologies (ART) now accounts for between 1% and 3% of annual births in many western countries and IVF services continue to grow. While these procedures provide an effective treatment for many infertile couples, they promote the transmission of any underlying genetic defects to the next generation. These genetic defects, therefore, need to be identified and understood. Recently it has been reported that the frequency of some rare diseases are, indeed, higher in ART offspring. Furthermore, if our hypothesis is correct and some of the genes involved are critical for chromosome integrity, then mutations in these genes may also increase the risk of cancer later in life.Read moreRead less
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.
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.