Determining The Impacts Of Epigenetic Modifying Drugs On Germline Programming And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$863,918.00
Summary
New drugs have been developed that inhibit specific enzymes that regulate epigenetic pathways in cells. These pathways significantly affect growth and development in offspring and may represent a risk to future children of patients taking the drug. This project will determine these risks and provide data for developing clinical guidelines for safe use of the drugs.
Genes to phenotype: Exploiting the marsupial model. This research will exploit one of Australia's finest natural resources, its marsupial fauna. The features of marsupial reproduction and development provide a unique opportunity to answer fundamental biological questions. This research will show how the minor differences in key developmental genes that have arisen in their 100 million year isolation give rise to the characteristic differences in developmental timing and reproduction between mar ....Genes to phenotype: Exploiting the marsupial model. This research will exploit one of Australia's finest natural resources, its marsupial fauna. The features of marsupial reproduction and development provide a unique opportunity to answer fundamental biological questions. This research will show how the minor differences in key developmental genes that have arisen in their 100 million year isolation give rise to the characteristic differences in developmental timing and reproduction between marsupials and other mammals. The focus on reproduction and development will also provide invaluable knowledge to underpin efforts to conserve our endangered species and to control those that are overabundant.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
Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupi ....Ancestral, conserved and novel mechanisms in marsupial genomic imprinting. Genomic imprinting is the differential expression pattern of some genes depending on whether the gene copy came from the mother or the father. This differential expression is essential for embryonic development and errors lead to disease. To date, most of our knowledge of the control of genomic imprinting comes from the mouse, but much less is known about this process in marsupials. Our comparative approach, using marsupial mammals that are distantly related to mice and humans, aims to clarify how genomic imprinting mechanisms have evolved, which patterns are conserved across mammals, and which vary. Our proposed research aims to provide new approaches and understanding of this fundamental process essential for the continuation of life.
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Reprogramming maternal and paternal genomes during development: new perspectives from marsupials. This project will use marsupials to examine programming of the germ cell lineage (cells that become eggs and sperm) and the evolution of these mechanisms that control their development. Using the unique features of our Australian native animals, this research will contribute to the understanding of the transmission of life.
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.
Extrinsic Control of Mammalian Germ Cell Delineation. Australia is a leader in the recent exciting breakthroughs in reproduction and development, such as cloning and embryonic stem cell propagation, and understanding how germ cells are specified would help us understand the biology underlying specification and developmental potential of all cells. This research will continue to contribute to maintaining Australia's high reputation in advances in reproductive biology. In addition, a greater under ....Extrinsic Control of Mammalian Germ Cell Delineation. Australia is a leader in the recent exciting breakthroughs in reproduction and development, such as cloning and embryonic stem cell propagation, and understanding how germ cells are specified would help us understand the biology underlying specification and developmental potential of all cells. This research will continue to contribute to maintaining Australia's high reputation in advances in reproductive biology. In addition, a greater understanding of marsupial reproduction is a high priority for Australia in the 21st century, with its current unacceptably high rate of mammalian extinctions, for 'we cannot conserve until we comprehend' (Short, 1985).The results therefore are of great potential benefit to society.
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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
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.
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.