Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Tuesday Speaker Abstracts

MULTISCALE REGULATION OF SARCOMERES IN HEALTH AND DISEASE Leslie A. Leinwand 1 ; 1 BioFrontiers Institute at the University of Colorado, Boulder, Boulder, CO, USA Muscle sarcomeres are complex mixtures of many interconnecting proteins. Our interests have long focused on the myosin motor protein family and how mutations in its members cause a variety of cardiac and skeletal muscle myopathies. With the knowledge gained from decades of study of these motor molecules and mutations in them, it has been possible to develop the first FDA-approved therapy for the most common inherited cardiomyopathy, hypertrophic cardiomyopathy. In this talk, I will describe the rationale for inhibiting MYH7 (AKA β -myosin) and how this same approach might be useful in treating a skeletal muscle myopathy caused by mutations in MYH7. One understudied area of muscle is driven by the fact that our cardiac muscle cells are as old as we are, but the contents of their sarcomeres and the rest of the proteomes need to be repaired and replaced. How are those processes regulated and how are they affected by different diseases, including myosin-based myopathies? We are using several approaches to study protein homeostasis in health and disease. We are pairing stable isotope labeling in wild type and genetic mouse models followed by mass spectrometry and imaging to generate spatial information about ages of sarcomeres, and individual protein by bulk protein half life determination.

WHAT DO MODELERS NEED FROM EXPERIMENTALISTS AND VICE VERSA? Malcolm Irving Kings College London, United Kingdom No Abstract

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