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.
Elucidating The Role Of Epididymosomes In The Transfer Of Fertility-modulating Proteins And Regulatory Classes Of RNA To Maturing Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$539,425.00
Summary
Sperm dysfunction represents a major underlying aetiology associated with male infertility. This proposal seeks to understand the mechanisms responsible for driving the functional maturation of spermatozoa and how these mechanisms are perturbed in response to environmental stressors.
Modulation Of MicroRNA Activity In The Testis: A New Paradigm For Male Fertility?
Funder
National Health and Medical Research Council
Funding Amount
$419,170.00
Summary
Sperm production in the testis is driven by the reproductive hormones, follicle-stimulating hormone (FSH) and testosterone. In this grant, we will investigate how a new class of molecules, called microRNAs, act to transmit the signals from FSH and testosterone to the cellular machinery of the testis, particularly at junctions between cells. This information has the potential to impact on our understanding of the causes of male infertility.
Role Of Snail Family Proteins In Male Fertility And Testicular Cancer
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Male fertility requires production of healthy sperm in the testis. This project builds on our discoveries that testicular cells regulate gene activity via the Snail family of proteins during sperm development, and that interruption of their activities reduces fertility in mice and fruitflies. Snail proteins are also active in cancer cells. We propose to study the precise steps in sperm production affected by Snail proteins and how they affect the progression of testicular cancer.
Facilitating Endometrial Receptivity To Improve Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$734,252.00
Summary
The womb prepares itself in each menstrual cycle for pregnancy and the implantation of an embryo. In some women, the endometrium may not prepare itself adequately and this can lead to infertility. We have identified small RNA that may be useful in predicting which women are not adequately prepared for implantation and may be used to develop treatments for infertile women, for which there are currently no treatments.
The placenta is essential for fetal-maternal exchange and healthy pregnancy however the factors that are required for the placenta to form are poorly understood. We will investigate how the placenta develops in mice and which are the most important factors that are required for a health placenta to form.
Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.
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.
The Importance Of The Blood-testis Barrier In Human Infertility
Funder
National Health and Medical Research Council
Funding Amount
$560,953.00
Summary
The blood-testis barrier (BTB) shields developing sperm from the circulation and immune system, which would see them as ‘foreign’. Loss of BTB function leads directly to infertility. Curiously, how the BTB ‘opens’ and ‘closes’ to allow entry without causing a ‘leak’ is unknown. We believe that activin A is the main gatekeeper, but this growth factor is also important in inflammation. Our goals are to show how activin A allows sperm cells entry, and how inflammatory diseases impact the BTB.
Determing Whether Breast Stem Cells Mediate The Risk Of Developing Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$433,894.00
Summary
Whilst the outcomes for women with breast cancer have improved significantly, the incidence of breast cancer continues to increase. Research needs to focus on prevention now to try to stop the increase. Apart from age, our reproductive behaviour is the largest risk factor for breast cancer. If a woman does not bear children, or has them after 35 years of age, she is at 25-50% increased risk of breast cancer. We would like to determine whether the breast stem cells play a role in this and why.