Fine Mapping Of A Significant Linkage Region For Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$518,250.00
Summary
Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors infl ....Endometriosis is a common disorder affecting up to 10% of women. In this condition, a special type of tissue that normally lines the inside of the womb (the 'endometrium') starts to grow outside the womb, mostly in the pelvis (lower abdomen). Common symptoms are severe pelvic pain, menstrual problems and infertility. The disease has a major impact on women's health, relationships, productivity and life choices. The mechanisms that cause endometriosis are not well understood. Genetic factors influence a woman's risk of developing endometriosis and finding genes and pathways leading to this disease would be a major advance. This will help design better approaches for the diagnosis, prevention and treatment of endometriosis. Since 1996, nearly 4,000 women with endometriosis plus their families have joined our genetic study. This includes around 1,000 families with two or more sisters who both have the disease. We have looked at the DNA from these sisters and found significant evidence for a gene or genes affecting endometriosis on one chromosome. No one else has linked this location with endometriosis. We are now focusing our efforts in the laboratory on this area, which contains approximately 250 genes. The aim of our new project is to study genes in the region in more detail to pinpoint the gene or genes responsible for risk of endometriosis.Read moreRead less
Genetic control of plant organ growth. Plants organs, such as leaves and petals, have a distinct size and shape reflecting differences in growth. Despite its importance, very little is known about the mechanisms that regulate growth. The objectives of this proposal are a) to test whether organ growth depends on cell-cell signalling and b) to identifying genes that regulate growth, and to characterize their molecular function.
Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the ....Marsupial germ cells and genes. Germ cells are the most fascinating cells in the body, since theirs is the unique responsibility for transmitting life from generation to generation. Studies in mice have suggested that position in the embryo determines their origin, but the early embryology of the mouse is so different from that of other mammals that the events need confirming and extending in another species. The simplified embryology of the tammar wallaby makes it ideal for studying one of the most fundamental questions in the whole of biology: what is the basis for the primal distinction between sex and soma?Read moreRead less
How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. ....How does the unilaminar blastocyst form an embryo? Marsupials are synonymous with Australia and they are scientifically amazing. An understanding how the single-layered marsupial blastocyst cells are directed to form the complex organisation of an embryo would help us understand the biology underlying the developmental potential of all cells. Understanding these processes is not only of great fundamental interest to developmental biology but also for the development of embryonic stem cell lines. This research will continue Australia's high profile in reproductive biology using one of our iconic native mammals. A greater understanding of marsupial reproduction will also contribute to management of our threatened marsupial populations.Read moreRead less
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, ....Identification of nuclear reprogramming factors in oocyte cytoplasm. The mature oocyte contains dominant factors that are capable of erasing tissue specific gene expression profiles of somatic cells. These reprogramming factors would be valuable for dedifferentiation of cells and for nuclear transfer in animal cloning. The research involves determination of reprogramming factors present in active cytoplasm following enucleation of the germinal vesicle, blockage of transcription and translation, and timed cultures. The assays will involve maintenance of reprogramming ability and erasure of somatic gene transcription. By subtractive elimination the function of isolated proteins which are involved in reprogramming will be identified for potential recombinant production.Read moreRead less
A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a proces ....A role for Cited2, Transforming Growth Factor-beta and matrix metaloproteinases in trophoblast invasion and placenta formation. The placenta is essential for the growth and development of the fetus, and if it fails to form correctly during pregnancy, it can have dramatic effects that can result death in utero, or adult onset diseases. Our research aims to understand how one protein functions in placenta formation. We will also investigate how this protein works at the molecular level in a process that enables single cells to respond to molecules sent from a distance by other cells (TGF-beta signalling). This process is also very important for a host of other biological processes relevant to human health, including cancer.Read moreRead less
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
A bird's eye view of sex: the chicken embryo as a model for gonadal development. The development of an embryo as either male or female (sex determination) is a fundamental biological process that fascinates both scientific and lay communities alike. This project will use the chicken embryo as a unique model organism to study how genes control sex determination. We will bring a novel method to our field of study; the use of avian viruses to deliver genes into embryos. This project will enhance ou ....A bird's eye view of sex: the chicken embryo as a model for gonadal development. The development of an embryo as either male or female (sex determination) is a fundamental biological process that fascinates both scientific and lay communities alike. This project will use the chicken embryo as a unique model organism to study how genes control sex determination. We will bring a novel method to our field of study; the use of avian viruses to deliver genes into embryos. This project will enhance our understanding of a basic biological process. It will have application to the poultry industry, in terms of sex ratio manipulation. It will also aid in the diagnosis of humans born with sexual abnormalities. The project will consolidate Australia's standing as a world leader in the area of reproduction and development.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less