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
Deciphering The Metabolic And Endocrine Profile Of Healthy Adipocytes
Funder
National Health and Medical Research Council
Funding Amount
$563,194.00
Summary
Obesity is associated with the development of metabolic diseases, however, it is becoming clear that it is where the excess fat is stored that is more important when predicting the health risks associated with obesity. This project aims to identify whether adipocyte progenitor cells, which eventually become fat cells, are ‘preprogrammed’ and whether differences in these cells explain the generation of either healthy or unhealthy fat in different locations of the body.
To Repair An Osteo-chondral Defect In An Experimental Rabbit Model Using A Structured 3D Nano-composite Scaffold Loaded With Mesenchymal Stem Cells (MSC)
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
The treatment of cartilage damage is a major problem in orthopaedic practice. The use of a 3D scaffold may overcome many challenges associated with cartilage and bone repair and regeneration. The aim of this research is to culture bone and cartilage cells into a prefabricated scaffold which may then be tested in an animal model. The results of this research may offer a new method of treating post-traumatic and osteoarthritic defects.
A Study Of Various Bone Scaffolds In A Maxillary Sinus Model
Funder
National Health and Medical Research Council
Funding Amount
$61,711.00
Summary
This project investigates using animal derived and artificial bone in regions of the mouth that are deficient and not suitable for replacing missing teeth using dental implants. Traditional techniques of bone replacement require the use of a patient's own bone. These procedures are associated with post-operative morbidity and this bone is present in limited quantity. The use of these bone replacements may overcome these challenges and eliminate the need for using patient's bone.
Comparison Of Periodontal Ligament Stem Cells And Induced Pluripotent Periodontal Ligament Stem Cells For Periodontal Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$831,955.00
Summary
In the first part of this study we will determine whether induced pluripotent stem cells or adult stem cells from the periodontal ligament are better candidates for periodontal regeneration. Secondly, using CAD/CAM technology we will make tissue engineering scaffolds tailored to fit periodontal defects and seeded with stem cells to improve on current techniques used to regenerate damaged tissues around teeth affected by periodontal disease.
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
Development Of Targeted Therapies To Reverse The Effects Of Ageing And Disease On Wound Healing And Tissue Generation
Funder
National Health and Medical Research Council
Funding Amount
$391,228.00
Summary
Despite success with the production of new tissues and organs in laboratory animals, tissue engineering in humans remains elusive. Emerging evidence suggests that ageing and diseases such as diabetes can adversely affect human stem cell regenerative capacity. Characterizing the effects of ageing and disease on stem cells during tissue generation is the first step in reversing these effects, paving the way for the production of new tissues and organs for use in human clinical trials.
Investigating Human Keratinocyte Stem Cells And Their Microenvironmental Niche
Funder
National Health and Medical Research Council
Funding Amount
$570,928.00
Summary
The stem cells in the outer protective layers of the epithelium of the skin (keratinocyte stem cells), possess an intrinsically high capability to regenerate tissue. However, this tissue regenerative ability can be enhanced by interactions with microenvironmental elements i.e. connective tissue cells and proteins. This study seeks to investigate specific keratinocyte-microenvironment interactions which will ultimately be used to improve current methods for generating skin tissue for burns patien ....The stem cells in the outer protective layers of the epithelium of the skin (keratinocyte stem cells), possess an intrinsically high capability to regenerate tissue. However, this tissue regenerative ability can be enhanced by interactions with microenvironmental elements i.e. connective tissue cells and proteins. This study seeks to investigate specific keratinocyte-microenvironment interactions which will ultimately be used to improve current methods for generating skin tissue for burns patients.Read moreRead less