The Regulation And Function Of Cadherin-mediated Adhesion Within The Zebrafish Myotome.
Funder
National Health and Medical Research Council
Funding Amount
$436,773.00
Summary
Co-ordinating how cells interact with their neighbours and where different cells are positioned within an organ is the role of proteins termed cell adhesion molecules. They delineate and sort cells into different groups depending on which cell adhesion molecules are expressed on their surface. Cell adhesion molecules are also important during the onset of disease, in particular cancer, where the levels and type of cell adhesion molecules expressed on the surface of a cancer cell can determine ho ....Co-ordinating how cells interact with their neighbours and where different cells are positioned within an organ is the role of proteins termed cell adhesion molecules. They delineate and sort cells into different groups depending on which cell adhesion molecules are expressed on their surface. Cell adhesion molecules are also important during the onset of disease, in particular cancer, where the levels and type of cell adhesion molecules expressed on the surface of a cancer cell can determine how invasive or aggressive the cancer cell will become. However, despite the fundamental importance that cell adhesion plays in sorting out cells in every tissue, the exact basis of cell migratory behaviours that occur within the intact organism remain poorly defined. We have examined the ability of specific members of a particular class of cell adhesion molecules, the classical Cadherins, to control formation of muscle. To do this we have examined muscle formation within embryos of the zebrafish, a small embryologically accessible fresh water fish. We have determined how different cadherin molecules co-ordinate the final pattern of the myotome, the structure that gives rise to the majority of muscle in the early embryo. We have determined that differential cell adhesion drives cell sorting of specific muscle cell types via differential use of members of the classical cadherin family of proteins. This study aims to look further at the way that these proteins are regulated in different muscle cells of the forming body. By understanding how these molecules regulate cell sorting and adhesion within the zebrafish myotome we hope to be able to apply this knowledge to how these molecules control the formation of more complex tissues. Furthermore, we believe the implication of specific signalling pathways in the control of cadherin gene expression has particular implications for the role these proteins play in the progression of metastatic cancer.Read moreRead less
Three Dimensional Ex Vivo Modelling Of Neuromuscular Junction Formation
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
Re-establishing functional connections between neurons and muscle is an important step in the recovery process after neuromuscular injury or surgery. In order to study the connection forming process in isolation a biological model of nerve muscle connection formation is required. This study aims to buid a biological model consisting of neurons and muscles in a three dimensional environment and to assess the quality of the functional connections that develop.
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.
Osteal Macrophages As Therapeutic Targets For Fracture Repair
Funder
National Health and Medical Research Council
Funding Amount
$618,015.00
Summary
Fragility fracture associated with osteoporosis is a substantial health problem costing $1.62 billion to treat in 2012 in Australia. There is no approved therapy to improve and accelerate fracture healing to help reduce this increasing health burden. This research will advance understanding of fracture repair in healthy and osteoporotic bone and progress development of a fracture therapy to improve bone repair by promoting specialised immune cells.
Molecular And Cellular Basis For Muscle Regeneration In Zebrafish.
Funder
National Health and Medical Research Council
Funding Amount
$541,104.00
Summary
Muscle repair occurs via the use of muscle stem cells, which provide skeletal muscle with its regenerative capacity. Muscle stem cells are particularly important in muscle diseases such as muscular dystrophies where muscle regeneration is an important factor in disease progression. We will identify the processes controlling muscle regeneration utilising zebrafish as a model organism. We hope this research will lead to an understanding of how muscle stem cells are generated.
Manipulating The Anabolic And Catabolic Responses For Bone Tissue Engineering
Funder
National Health and Medical Research Council
Funding Amount
$58,202.00
Summary
The repair of large bone defects represents a significant clinical problem. Evolving tissue engineering technologies may lead to significant improvements in orthopaedic treatments for these problems. We plan to compare novel biological approaches designed to maximise new bone formation while preventing bone resorption with existing synthetic graft materials. Our research data will be readily translated from the laboratory to a clinical setting.
The Role Of Scube Genes In Hedgehog Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this ....Cancer often results form the miss-regulation and-or mutation of genes that control tissue formation in the developing embryo. Particular sets of genes combine to form a signal transduction pathway that coordinates the cell's response to its environment during the course of normal fetal growth. One such pathway is called the Hedgehog signal transduction pathway which has been shown to coordinated cell division and patterning within malignant and normal tissues. Genes encoding components of this pathway are mutated in the most common forms of human cancers. Understanding how this pathway is regulated is critical to designing strategies to treat the onset and progression of these cancers. The studies outlined in this grant plan to study a new component of this pathway that we have identified in our laboratory, in an easy to study vertebrate model, the zebrafish embryo. We plan to study how this class of proteins, termed scube proteins, acts to control activation of the pathway. We hope this will lead to a fuller understanding of this process, and at the same time help understand the nature of the end result of the patterning process within the muscle cells that we are studyingRead moreRead less
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
The Role Of Grb10 In The Regulation Of Muscle Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Obesity increases the risk of metabolic diseases such as type 2 diabetes. Muscle is a key tissue for balancing whether energy is used or stored as fat and as we age, muscle mass normally decreases making maintaining a healthy metabolism even more difficult. We have discovered that removing the Grb10 gene from mice produces bigger muscles. This project will investigate the mechanisms of this effect so that strategies can be developed to regulate muscle mass and improve metabolic health