Recycling Of E-cadherin: Implications For Dynamic Cell Adhesion
Funder
National Health and Medical Research Council
Funding Amount
$250,494.00
Summary
E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and ....E-cadherin is one of the major proteins responsible for mediating cell-to-cell adhesion in the body. During embryonic development E-cadherin is essential for establishing the normal body pattern and the cellular architecture of many epithelial organs. Throughout life E-cadherin serves to maintain epithelial barriers, such as the lining of the digestive tract. E-cadherin has been clearly identified as a tumour suppressor molecule: loss of normal E-cadherin function leads to tumour metastasis and cancer invasion. It is therefore essential to understand the physiological function and regulation of E-cadherin in cells. E-cadherin is normally expressed on the surface of cells for adhesion to neighbouring cells. Recently, we found that cells can internalise and recycle this surface E-cadherin: even in mature epithelia, a proportion of the E-cadherin molecules appear to undergo constant movement in and out of the cell. It is likely that this mechanism participates in the dynamic remodelling of adhesive contacts between cells in organs such as the gastrointestinal tract and during wound healing. Corruption of this recycling mechanism could also potentially contribute to tumorigenesis. In this grant we propose to build upon this discovery by investigating molecular and cellular mechanisms that mediate E-cadherin recycling. We will characterize the cellular pathways by which E-cadherin is trafficked. The signaling pathways that regulate recycling will be analysed, since these may be perturbed in cancer and inflammation. Other molecules that interact with E-cadherin will be studied to determine whether they too recycle. The information from these studies will have broad implications for understanding the role of E-cadherin in healthy organs and in common cancers.Read moreRead less
Early Influences Of Obesity And Fat Patterning In Children:critical Periods, Environmental Determinants, And Socio-cultu
Funder
National Health and Medical Research Council
Funding Amount
$1,152,711.00
Summary
Childhood obesity is an escalating public health problem both internationally and within Australia. Rates of childhood obesity in Australia are at one of the highest amongst developed nations. 25% of Australian children are currently overweight or obese. Obesity is a strong risk factor for chronic disease. In children, obesity is of concern because it is highly likely to persist and, during childhood, contributes to serious physical and mental health problems. A quarter of Australian children ar ....Childhood obesity is an escalating public health problem both internationally and within Australia. Rates of childhood obesity in Australia are at one of the highest amongst developed nations. 25% of Australian children are currently overweight or obese. Obesity is a strong risk factor for chronic disease. In children, obesity is of concern because it is highly likely to persist and, during childhood, contributes to serious physical and mental health problems. A quarter of Australian children are now carrying excess body fat. Because of these factors, prevention of obesity is paramount because success of current treatment options is limited and does not last. Especially harmful forms of fatness may originate in early life - the tendency to store fat in the abdominal region and the tendency to accrete fat rather than muscle (at any body size). For this reason, the early life determinants of obesity deserve special attention, even in the presence of society-wide factors conducive to obesity. Professor Moore and a group of researchers from the University of Adelaide will test the proposition that pre-birth and infancy is a ‘critical period’ for the development of obesity. The group aims to investigate whether there is a distinct period in early life for acquiring the predisposition to harmful forms of fatness. The project also aims to identify practical opportunities for prevention, focusing on mothers and their infants.Read moreRead less
Functional Screening Of Novel Genes In Craniofacial Development
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Our faces are central to our ability to communicate, feed, breath and interact with each other. Birth defects that impact on the normal development of the face are common and affect not only the child but have a dramatic impact on the child's family as well. The genetic causes of most facial birth defects are unknown. This project will develop a method for determining how development of the face is controlled and will help identify genes that are responsible for facial birth defects.
Genetic And Molecular Dissection Of Laterality In The Developing Heart
Funder
National Health and Medical Research Council
Funding Amount
$379,370.00
Summary
Vertebrate animals display an external bilateral symmetry. However, most internal organs are located asymmetrically and show profound left-right structural asymmetries during development. For each species, these laterality characteristics are constant. Inherited laterality disorders occur in humans and, although rare, are associated with high mortality rates due to discordant cardiovascular development. Moreover, subtle anomalies of laterality may underlie a host of congenital heart abnormalitie ....Vertebrate animals display an external bilateral symmetry. However, most internal organs are located asymmetrically and show profound left-right structural asymmetries during development. For each species, these laterality characteristics are constant. Inherited laterality disorders occur in humans and, although rare, are associated with high mortality rates due to discordant cardiovascular development. Moreover, subtle anomalies of laterality may underlie a host of congenital heart abnormalities. In early embryogenesis, the newly-formed heart tube loops to the right, an event which establishes the correct alignment of the future cardiac chambers. The direction of heart looping is determined by genetic pathways that establish laterality in the early embryo. A component of this pathway is a TGFbeta-family signalling molecule, nodal, which is activated on the left side of the forming heart and other organs. Nodal then activates the transcription factor gene Pitx2. The aim of this project is to examine the consequences of genetic inactivation of the mouse nodal and Pitx2 genes in the heart, and to discover cardiac genes downstream of these genes. We will specifically test the hypothesis that laterality contributes to heart chamber formation in addition to setting the direction of looping. Ablation of these genes in the whole embryo leads to complex defects that preclude analysis of their functions in the heart. To achieve heart-specific deletion, we will use a conditional gene ablation technology that exploits the bacteriophage recombinase, Cre. Genes downstream of Pitx2 and Nodal will be discovered using microarray technology, which allows us to screen exhaustively for changes in gene expression between different tissues. This project will help us solve the complex genetic basis of congenital cardiac abnormalities in humans, and will contribute to our understanding of how heart chambers form, potentially useful in stem cell-based therapies for the failing heart.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.