Reference number : GC-2017-Q1-02548, amendment number : , agreement type : G, recipient legal name : Pilgrim, David (University of Alberta), recipient country : CA, recipient province : nan, recipient city : Alberta, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : The contractile sarcomere of striated muscle is one of the most complex cellular protein assemblies, and we have studied the major components for decades. In contrast, the precise steps in the assembly of sarcomeres, as well as the homeostatic processes that maintain them during activity are poorly understood at the cellular or molecular level in any system. We know the components of muscle, but little about how they are assembled, or disassembled following damage. Quality control (QC) regulation of protein folding and homeostasis, as well as staged assembly of proteins in time and space, is critically important. Our program is to understand the molecular pathways that assemble and maintain the sarcomere, or allow repair or regeneration after damage. The focus of this proposal will be on the transcriptional control networks that regulate synthesis of sarcomere components, the posttranscriptional QC regulation of thick filament assembly, and the coordination between the two during normal development, as well as when the structure of the sarcomere is perturbed by genetic lesion. The aims are: (i) determine the molecular pathway of sarcomere patterning and assembly in skeletal and cardiac muscle, focusing on Protein Quality Control aspects; (ii) test predictions of this model i n vivo ; and (iii) use genetics to uncover novel components of this pathway. The zebrafish model system provides the power of genetics and genome editing technologies, as well as the ability to follow the process in a living transparent embryo in vivo . The structural and catalytic factors involved in the process of myogenesis are remarkably conserved, and we have been able to build upon our earlier work in C. elegans to provide key insights into these processes., program purpose french : The contractile sarcomere of striated muscle is one of the most complex cellular protein assemblies, and we have studied the major components for decades. In contrast, the precise steps in the assembly of sarcomeres, as well as the homeostatic processes that maintain them during activity are poorly understood at the cellular or molecular level in any system. We know the components of muscle, but little about how they are assembled, or disassembled following damage. Quality control (QC) regulation of protein folding and homeostasis, as well as staged assembly of proteins in time and space, is critically important. Our program is to understand the molecular pathways that assemble and maintain the sarcomere, or allow repair or regeneration after damage. The focus of this proposal will be on the transcriptional control networks that regulate synthesis of sarcomere components, the posttranscriptional QC regulation of thick filament assembly, and the coordination between the two during normal development, as well as when the structure of the sarcomere is perturbed by genetic lesion. The aims are: (i) determine the molecular pathway of sarcomere patterning and assembly in skeletal and cardiac muscle, focusing on Protein Quality Control aspects; (ii) test predictions of this model i n vivo ; and (iii) use genetics to uncover novel components of this pathway. The zebrafish model system provides the power of genetics and genome editing technologies, as well as the ability to follow the process in a living transparent embryo in vivo . The structural and catalytic factors involved in the process of myogenesis are remarkably conserved, and we have been able to build upon our earlier work in C. elegans to provide key insights into these processes., agreement title english : Muscle Protein Complex Assembly and Maintenance, agreement title french : Muscle Protein Complex Assembly and Maintenance, agreement number : RGPIN, agreement value : 28000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2018-2019), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2018-2019), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada