Impact Of The Extraembryonic Tissues On Early Embryonic Development: Genetic Basis Of Abnormal Body Plan
Funder
National Health and Medical Research Council
Funding Amount
$316,326.00
Summary
An important milestone of early development is the attachment (or implantation) of the embryo to the wall of the womb through the action of a specialized population of cells known as the trophoblasts. The early conceptus comprises not only cells that make up the embryo but also those (called extraembryonic cells) that later forms the placenta, and the membranes that wrap around the developing fetus. The placenta and the membranes are indispensable for the normal fetal growth by providing the eff ....An important milestone of early development is the attachment (or implantation) of the embryo to the wall of the womb through the action of a specialized population of cells known as the trophoblasts. The early conceptus comprises not only cells that make up the embryo but also those (called extraembryonic cells) that later forms the placenta, and the membranes that wrap around the developing fetus. The placenta and the membranes are indispensable for the normal fetal growth by providing the effective nourishment and protection for the developing fetus. Recent studies in the mouse have revealed that normal development of the recently implanted conceptus depends on the reciprocal interaction of the embryonic and extraembryonic cells. Abnormal embryo may form if the non-embryonic cells do not differentiate normally, as seen in the situation when an X-chromosome is lost from the female embryo (as in 45X0 Turner syndrome) and in early conceptus that carries a gene mutation that affects the production of growth factors by the extraembryonic cells. Functional deficiency of the extraembryonic cells might be a cause for early pregnancy loss where the conceptus has successfully implanted but the embryo fails to form. The remarkable conservation of the molecular mechanism that controls mammalian development allows us to use the mouse embryo as a genetic model for human development. The proposed project is designed to examine in a laboratory mouse model the molecular and cellular factors that regulate the activity of the extraembryonic cells. Specifically, we focus on a gene known as Sox17, which may be involved with the differentiation of the extraembryonic cells. We will study the impact of the mutation of this gene on the development of the early embryo to test the hypothesis that the extraembryonic cells may fulfill an important function in ensuring normal embryo formation, in addition to the other roles of nourishment and mechanical protection of the fetus.Read moreRead less
Head Development: Genetic Determinants And Tissue Potency
Funder
National Health and Medical Research Council
Funding Amount
$947,116.00
Summary
Congenital malformations involving major defects of brain (anencephalus and related anomalies) and facial structures (ear, face and neck) are encountered in 3.4 and 1.4 per 10000 births respectively (Congenital Malformations Australia 1981-1996, National Perinatal Statistics Unit) and they constitute a substantial clinical burden. It is believed that these major structural defects usually result from abnormal development in the first trimester, which coincides with the time frame for the formati ....Congenital malformations involving major defects of brain (anencephalus and related anomalies) and facial structures (ear, face and neck) are encountered in 3.4 and 1.4 per 10000 births respectively (Congenital Malformations Australia 1981-1996, National Perinatal Statistics Unit) and they constitute a substantial clinical burden. It is believed that these major structural defects usually result from abnormal development in the first trimester, which coincides with the time frame for the formation of the basic components of the embryonic head in the mouse. Knowledge of the formation of the head in the mouse model is therefore relevant to the understanding of related developmental processes in early human development. This project which involves the application of sophisticated embryological and molecular analyses on mouse embryos generated by transgenesis and genetic manipulation provides a detailed studies of craniofacial morphogenesis in a mammalian model for early human development. The micro-manipulation procedures, embryo culture, fluorescence microscopy and the in situ hybridization are routinely performed in our laboratory, and most of the mouse lines are well established in my laboratory. Experiments proposed for this project that focus on the embryological and molecular analysis of normal and mutant embryos should discover new information on the cellular and molecular mechanisms that regulate head development. The knowledge will also offer insight into the pathogenesis of similar craniofacial malformations in other mutant embryos.Read moreRead less
Periodontal Mesenchymal Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$358,000.00
Summary
Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characteriz ....Dental diseases affecting the gums (periodontal disease) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised masticatory function. If left untreated, the associated pain and loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Dental diseases affecting the gums (periodontal diseases) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cell ....Dental diseases affecting the gums (periodontal diseases) are extremely prevalent in our society. The effects of periodontal disease can be particularly severe as loss of support for the teeth leads to loose teeth and severely compromised chewing function. If left untreated, the associated loss of function may necessitate extraction of the teeth. We have recently identified cells residing in the periodontal ligament which may be adult stem cells. This project will further characterize these cells and explore whether they can be used to restore periodontal tissues damaged by periodontal disease.Read moreRead less
Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and ....Periodontal disease is an inflammatory disorder leading to tooth loosening and, if untreated, tooth loss. Once bone destruction has occurred around teeth the treatment outcomes are severely compromised and are mainly focussed towards slowing the process of destruction rather than repairing the damage. Over the last decade, treatment of advanced periodontal disease has focussed on ways in which the damaged tissues may be regenerated. We now have gained considerable insight into the molecular and cellular events associated with periodontal regeneration. Despite efforts to induce regeneration through the selective use of growth and differentiation factors it is becoming obvious that the most significant factor in successful clinical outcomes is the recruitment of special cells to the site of damage which have the potential to repair tissue damage. Thus, we intend to engineer different types of periodontal matrices in the laboratory and then transplant these newly formed tissues into sites affected by periodontal disease in an attempt to repair the damage caused by the disease process.Read moreRead less
The Role Of Perlecan In Tensional Connective Tissues
Funder
National Health and Medical Research Council
Funding Amount
$605,037.00
Summary
Musculoskeletal diseases affect tension and weight bearing connective tissues which have notoriously poor repair capabilities. These conditions are difficult to treat clinically and surgical repair in many cases does not provide a return to optimal joint function impinging on the quality of life of afflicted individuals and their carers. Our project aims to better understand the structure and function of these tissues in health and disease with a view to improving repair strategies.
Developing In Vivo Methods Of Adipose Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$374,703.00
Summary
Surgical repair and replacement of soft tissues after tumour removal or to repair existing damage requires fat tissue with a good blood supply. Tissue engineering allows us to create new fat grafts for replacement tissue without causing unnecessary pain or trauma to the patient. We have developed a method for growing fat tissue using a chamber to maintain a space for the tissue to grow into, a blood vessel to supply nutrients to the growing tissue, cells or tissue from the host to encourage cell ....Surgical repair and replacement of soft tissues after tumour removal or to repair existing damage requires fat tissue with a good blood supply. Tissue engineering allows us to create new fat grafts for replacement tissue without causing unnecessary pain or trauma to the patient. We have developed a method for growing fat tissue using a chamber to maintain a space for the tissue to grow into, a blood vessel to supply nutrients to the growing tissue, cells or tissue from the host to encourage cell growth and migration and a matrix or scaffold to support the developing tissue and guide it to form the type of tissue we want (fat, muscle etc). We have shown that the tissue graft may cause fat to grow due to causing an inflammatory reaction and confirmed this by adding a mild inflammatory compound to the chamber instead of a tissue graft. This compound caused the chamber to grow fat tissue. The aim of this project is to determine which of the growth factors or other signaling factors released by the inflammation process is responsible for causing fat tissue production and to identify what cells are being attracted to the chamber to help grow the fat, so that we can further improve our engineering of fat tissue. Understanding the pathways which mediate or stimulate fat growth will provide new opportunities for improving fat growth and allow the engineering of larger fat grafts in larger animals and eventually human clinical application. Beyond that, inflammation is involved in many disease processes (eg. obesity, metabolic syndrome, diabetes, cancer), and these fields of study will also benefit from our research.Read moreRead less