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.
Progesterone Receptor-mediated Coordination Of Oocyte-oviduct Communication During Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$86,128.00
Summary
Infertility affects 1 in 6 couples, often due to failed release of an egg from the ovary. The hormone progesterone is essential for this process. Our goal is to determine how progesterone signals the egg to ensure its correct release into the oviduct where fertilization may occur. To identify these signals, experiments will analyse ovary cells and eggs of mice, including mice that do not respond to progesterone. The results will provide much needed information about female reproductive health.
The Mechanism Of Spermatid Differentiation - A Link To Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$506,425.00
Summary
To discover novel regulators of male fertility, we have screened libraries of mutant mice generated by a chemical mutagen. This project aims to define the function of the mutated gene identified in a male-specific infertile mutant mouse line. The mutated gene has been proposed to play a role in regulating cell death and suppress lung tumour formation. Our data may reveal novel options for male infertility treatment and for the development of male contraception and lung cancer biomarkers.
A New Model Of Asthenospermia And A Candidate Gene For Multiple Ciliopathies
Funder
National Health and Medical Research Council
Funding Amount
$629,039.00
Summary
Though the analysis of a unique mouse strain (Mot1) we have identified a previously unknown cause of male infertility and lung disease. We hypothesis that the Mot1 line is a model of human primary cilia dyskinesia and that the Mot1 protein is involved in cilia function. Within this project we will define the consequences of a loss of Mot1 protein function, we will define its binding partners and we will screen for mutations in the corresponding human gene.
Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide, yet its origins remain unknown. Androgens are implicated in the development of PCOS, but the decisive, invasive studies needed to confirm and elucidate their roles are not feasible in women. Hence, using our innovative mouse models of androgen resistant female mice, this study will determine the role of androgens in PCOS aiming to better understand, and identify new treatments for this common female reproductive disorder.
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.
Hormonal Control Of Serotli Cell Maturation And Function
Funder
National Health and Medical Research Council
Funding Amount
$512,898.00
Summary
This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR ac ....This project will determine the key roles of androgen in the Sertoli cell, a unique highly specialised cell that provides essential nutritional and structural support for sperm production. Androgen acts via the androgen receptor (AR), which is vital for initiating and maintaining sperm development. In current NHMRC-funded research we successfully established new mouse models designed to study AR, in particular its regulation of gene expression, in the Sertoli cell. We revealed that genomic AR activity within Sertoli cells is essential for 'induction' of complete sperm development. Ongoing work will develop unique 'inducible' transgenic models that will allow, for the first time, selective analysis of Sertoli AR in both 'developing' and 'adult' testes. Our innovative models will allow AR function to be switched on or off at any stage of development, providing unique opportunity to determine the key AR-regulated factors and pathways controlling induction, maintenance or restoration of sperm production. In past NHMRC research we created a novel transgenic model to study another major reproductive hormone, FSH. Using the hormone-deficient background of 'hpg' mice, we found that androgen and FSH act synergistically in the developing 'meiotic' germ cells that form sperm. Using the latest microarray gene technology we generated datasets of androgen-regulated genes with or without FSH activity, which combined with our unique transgenic AR and FSH models, will be used to identify key pathways, including those enhanced by androgen-FSH synergism, in the early testicular response. Our research will provide new knowledge of the precise roles and pathways of testicular AR actions, to ultimately identify key genetic and regulatory factors as targets for significantly improved therapy for male infertility, gonadal tumours, or contraception.Read moreRead less