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.
Finding The Missing Katanin Required For Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$417,214.00
Summary
Microtubules are a key element of all cells, including in the male germ line. In this project we will define the function of the microtubule severing protein KATNA1 in male fertility. This will be achieved using a unique model and state-of-the-art technologies. This project will have immediate relevance to the 1 in 20 Australian men who suffer from infertility but will also inform KATNA1 function in the many other tissues where KATNA1 is produced.
The Characterisation Of An Essential Regulator Of Pre-mRNA Splicing Required For Germ Cell Function And Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$1,116,739.00
Summary
The male germ line is a fantastic system within which to define processes of fundamental importance to cell biology and health broadly. Within this grant we will define the role of a poorly described RNA splicing factor in all of stem cell function (spermatogonia), meiosis (spermatocytes) and in the remarkable metamorphosis underlying spermatid maturation. This will be done using a range of phenotypic characterizations, CHIP and RNA Seq technologies and gene sequencing.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
The Identification Of Male Meiosis Genes Using A New Mouse Line And Human Genome Scans For Gene Copy Number Variations
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Infertility affects 1 in 25 Australian men and meiosis is a key process in male fertility, yet we know very little about the mechanisms that control it. We will use a new point mutant mouse model of meisois failure to identify a novel regulator of male fertility. Further, we hypothesize that changes in gene copy number will lead to meiosis arrest and infertility in some men. Such variations will be assessed through a whole genome scan of a unique set of infertile men.
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
The Role Of FSH And FF-MAS In The Induction Of Meiotic Resumption In The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order ....About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order to produce many eggs, thereby increasing the success rate per treatment cycle. But stimulation of ovarian function involves a number of drawbacks including cost of fertility drugs, continued monitoring, discomfort and risk of complications (eg. ovarian hyperstimulation syndrome). It is evident that novel methods for the production of mature eggs in vitro in the absence of ovarian stimulation would mark a breakthrough, making assisted reproduction a more friendly discipline. In general, all IVF patients would benefit from in vitro maturation techniques. In particular, in selected patients (eg. those suffering from polycystic ovary syndrome) the advantages of this method might prove to be invaluable, by achieving production of fully viable eggs under controlled conditions, as opposed to in vivo where oocytes generally fail to acquire full competence, having been subjected to an unfavourable hormonal environment. Unfortunately, attempts to treat IVF patients using eggs matured in vitro has been disappointing so far, with only occasional pregnancies reported over the last decade. Clearly, this is due to lack of knowledge of the fundamental events occurring during egg maturation, as well as the paucity of biological material available for experimentation. So, to make in vitro maturation of eggs a successful fertility treatment we undoubtedly need to achieve a more profound insight into the function of the egg, the first step being to focus our attention upon experimental models.Read moreRead less