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.
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
Role Of The MicroRNA MiR144 In Haemopoiesis In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
Recently a new form of gene regulation has been discovered involving small RNA molecules called microRNAs (miRNAs). Although vertebrates (like man, mouse and fish) contain many hundreds of miRNAs, the function and true gene targets of each individual miRNA are largely unknown. A better understanding the normal function and targets of miRNAs is needed so that their role in normal biology and disease development can be understood. These studies exploit the technical strengths of zebrafish, an mode ....Recently a new form of gene regulation has been discovered involving small RNA molecules called microRNAs (miRNAs). Although vertebrates (like man, mouse and fish) contain many hundreds of miRNAs, the function and true gene targets of each individual miRNA are largely unknown. A better understanding the normal function and targets of miRNAs is needed so that their role in normal biology and disease development can be understood. These studies exploit the technical strengths of zebrafish, an model of increasing importance in biomedical research, to study the function of a particular miRNA, miR144, and to identify its physiological target genes. Zebrafish have several advantages for studying miRNA function - several simple methods for experimentally altering miRNA levels are standard in zebrafish but not easy in other models like mice. miR144 has been chosen because it has an expression pattern that strongly suggests a role in blood development. Blood development and zebrafish technologies are central themes of the Lieschke laboratory. Preliminary experiments in zebrafish have shown that miR144 expression can be detected in blood cells, that it is functionally active when overexpressed, that its effect can be intercepted, and that there are blood-system effects of its misexpression, particularly in mutant zebrafish with abnormalities of blood development that provide a sensitized background for such studies. These studies will describe the expression of miR144 in detail in normal and abnormal zebrafish blood development. The effects of miR144 overexpression and knock-down of expression will be studied in detail. To identify the targets of mir144, a multifaceted microarray analysis will be performed, and the validity of candidate targets suggested by this will then be systematically tested. When finished, these studies will have characterised the physiology of this new blood regulator and identified the way it exerts its effect.Read moreRead less