Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular fun ....Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular functions of MT-severing enzyme FIGNL1 and key MT glutamylation enzymes (CCP1, CCP5 and TTLL1). Insights will be generated using sperm production as a model system and will thus inform the mechanisms by which fertile sperm are built, in addition to being relevant to cell biology across eukaryotic species. Read moreRead less
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.
Women are born with a limited supply of eggs and are unable to make new eggs after birth. Because of this, the number and health of eggs established within the ovary early in life influence the length of time for which a female will be fertile, her age at menopause, and the health of her offspring. This project aims to shed some light on the mechanisms that control egg supply and reproductive longevity in women by investigating the role of the cell death protein Bid within the ovary.
Role of Musashi in the regulation of cell cycle proteins. We have identified a protein family that directs cell fate and maintains male fertility. This project will provide new avenues for generation of contraceptives in male animals and to regulate stem cells for production of specialised cell types in biotechnological applications.
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.
Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and and ....Much of our current knowledge on development of external genitalia (ExG), the penis and clitoris, comes from 20 &70 year-old studies (1); but with significant developments in contemporary imaging and new mouse models, we have new data. The overall goal of this project is to prove the hypothesis that penile and clitoral development is estrogen- (and androgen-) dependent and, to show that the administration of exogenous endocrine disrupting chemicals that alter the balance between estrogen and androgen will disrupt ExG development.Read moreRead less
Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expect ....Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expected to result in disciplinary collaboration, produce novel models, and promote future projects in many species. The project should result in significant benefits toward advancing knowledge in reproductive biology, have economic and commercial benefits, and further enhance Australia's outstanding reputation in the field.Read moreRead less
A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims ....A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims to define the mechanisms underlying KATNAL2 function in the male germ line. It is expected that these data will generate a comprehensive picture of KATNAL2 function and provide foundation data of relevance across multiple species and tissues. In the longer term, it may also reveal a rational strategy for fertility enhancement or suppression.Read moreRead less
The control of meiosis in mammalian oocytes. This study will elucidate how the egg undergoes its final steps in preparation for fertilisation and early development. This will produce greater knowledge about how eggs develop, which may reveal new approaches to modulating reproductive capacity.
The Long-term Consequences Of Assisted Reproduction On The Growth, Metabolic, Respiratory, Psychological, Immunological And Reproductive Development Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$1,552,096.00
Summary
1 in 25 children are born from IVF treatment - incredibly- to our shame; no data exists as to the long-term health of these children. Presented is a unique opportunity, which would be exceedingly difficult to replicate elsewhere in the world, to determine the long-term consequences of IVF upon the development of the offspring, by comparing their growth, metabolic, respiratory, psychological, immunological and reproductive development to a representative sample of WA children- the Raine cohort.