How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) acti .... How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) active destruction and (2) passive dilution. The results will help explain how heteroplasmy is avoided in order to maintain the fitness of organisms including animals and humans. The results will have long term insights into improving breeding in agriculture and in the prevention of mitochondrial genetic disease.Read moreRead less
Understanding why mammalian eggs have so much mitochondrial DNA . During oocyte growth there is massive increase in the replication of mitochondrial DNA so that each ovulated egg has 200,000-400,000 copies of the mitochondrial genome. This mitochondrial compliment will provide the template for all mitochondrial DNA in the subsequent organism. The established role of mitochondria is to provide energy in the form of ATP, but they are also known to be highly adaptive to the metabolic and energetic ....Understanding why mammalian eggs have so much mitochondrial DNA . During oocyte growth there is massive increase in the replication of mitochondrial DNA so that each ovulated egg has 200,000-400,000 copies of the mitochondrial genome. This mitochondrial compliment will provide the template for all mitochondrial DNA in the subsequent organism. The established role of mitochondria is to provide energy in the form of ATP, but they are also known to be highly adaptive to the metabolic and energetic state of the cell. In this project, we will use genetic approaches to decrease the amount of oocyte mitochondrial DNA by 90%. We will examine how this influences mitochondrial organisation, oocyte metabolism and embryo development. This new knowledge will provide insights into animal breeding and human health.Read moreRead less
Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blo ....Going with the flow: directing nutrient rich blood to the brain. This project aims to visualise and measure flow of blood from the umbilical cord to the fetal brain and to understand how delivery of oxygen and glucose to the brain is prioritised by constriction or relaxation of a specialised shunt, the ductus venosus. The project will directly and non-invasively measure this fundamental phenomenon with novel MRI protocols. Expected outcomes of this project include advances in measuring fetal blood flow and the exchange of expertise between leading researchers in Australia and Canada. In the long-term, this will enhance Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.Read moreRead less
Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow ....Opening and closing doors in the fetal circulation impacts brain metabolism. This project aims to measure blood flow from the umbilical cord through special shunts or doors to the fetal brain and to understand how changes in delivery of oxygen may impact fetal brain metabolism. This fundamental phenomenon will be measured with novel MRI protocols developed by a multidisciplinary, international team. Expected outcomes of this project include world-leading advances in measuring fetal blood flow and brain metabolism with exchange of expertise between leading researchers in Australia and Canada and their trainees. In the long-term, this should provide significant benefits in enhancing Australia’s research capacity in fetal physiology and may lead to new tools for monitoring or supporting fetal development.Read moreRead less
Gamete-specific knockout of Fizzy-Related to examine its meiotic role in oocytes and sperm. Fizzy-Related is a gene that appears to be essential in making an ovulated egg, and it may also have an important role to play in making sperm. A mouse knockout will be generated to examine exactly how it functions; because it affects the egg number remaining in the ovary and egg quality Fizzy-Related may be eventually an important therapeutic target.
Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.Read moreRead less
Impact of the male germ line on the mutational load carried by mammalian embryos. This project examines whether a man's age or exposure to lifestyle factors (alcohol, cigarette smoke and mobile phone radiation) can have a major effect on the health of his children. The project is particularly relevant to the safety of assisted conception procedures used to treat the 1 in 20 Australian men suffering from infertility.
Defining signals that regulate intestinal stem cells during organ growth. This project will define the key signals that promote cell division in the stem cells which produce the inner epithelial lining of the gut. This fundamental knowledge is of significance as it will provide information about how key signals are delivered to promote repair of injury to this key cell layer. The gut is a vital organ conserved across species that is prone to injury as it is exposed to a very harsh environment of ....Defining signals that regulate intestinal stem cells during organ growth. This project will define the key signals that promote cell division in the stem cells which produce the inner epithelial lining of the gut. This fundamental knowledge is of significance as it will provide information about how key signals are delivered to promote repair of injury to this key cell layer. The gut is a vital organ conserved across species that is prone to injury as it is exposed to a very harsh environment of bacteria and the products of food digestion. The outcomes of this project will provide an understanding of development and regeneration of the epithelial lining and key signals that may augment repair. The future benefits include improved health outcomes for animals and humans and potential economic benefits.Read moreRead less