Monday, July 17, 2023

8:15 - 20:00

8:15 - 8:30
Opening Remarks
Michael Regnier, University of Washington, USA and Michael Geeves, University of Kent, United Kingdom

Session I:  MD/BD Simulations of Myofilament Proteins
Co-chairs: Anne Houdusse, Institut Curie, France
                     Matthew Childers, University of Washington, USA

8:30 - 8:50 
Anne Houdusse, Institut Curie, France
Small Molecules Modulating Force Production: A New Perspective Against Muscle-Associated Diseases

8:50 - 9:10 
Matthew Childers, University of Washington, USA
Using 2'-Deoxy-ADP to Probe Stability of the Myosin Interacting Heads Motif at Atomic Resolution

9:10 - 9:30 
Ian Gould, Imperial College, United Kingdom
An In-Silico Investigation of the Effects of Small Molecules that Restore the Effects of Phosphorylation to
Uncoupled Thin Filaments due to Cardiomyopathy-causing TNC G159D Mutation

9:30 - 9:50 
Michael Rynkiewicz, Boston University, USA
Modeling the Troponin Core Domain on Thin Filaments Using Data From Cryoelectron Microscopy and
Fluorescence Approaches

9:50 - 10:00
Brett Colson, University of Arizona, USA*
Hypertrophic Cardiomyopathy Mutations in Cardiac Myosin-Binding Protein C N-Terminal Domains
Cause Local and Allosteric Effects on Protein Mobility and Increase Actin Binding

10:00 - 10:30 | Coffee Break

Session II: Integrating Computational Models at Different Spatial and Temporal Scales
Co-chairs: Daniela Valdez-Jasso, University of California, San Diego, USA
                     Joseph Powers, University of Washington, USA

10:30  - 10:50 
Daniela Valdez-Jasso, University of California San Diego, USA
Multiscale Modeling for Determine Sex Differences in Resting and Active Myocardial Material Properties 
in a Rat PAH Model

10:50 - 11:10 
Joseph Powers, University of Washington, USA
Integrating Multiscale Computational Models and Experimental Biomechanics to Investigate the Contractility
Filamin C Deficient Hearts

11:10 - 11:30 
Srba Mijailovich, Filamentech, USA
Integration of Multiple Experiments by Multiscale Computational Modeling

11:30 - 11:50 
Kyoko Yoshida, University of Minnesota, USA
Multiscale Model Predictions of Heart Growth Applied to Postpartum and Hypertensive Pregnancies

11:50 - 12:00 
Amadeus Gebauer, Technical University of Munich, Germany*
A Constrained Mixture Model of Sarcomere Turnover in Cardiomyocytes for Organ-Scale Cardiac
Growth and Remodeling

12 00- 13:00 | Lunch Break

Session III: Do We Have an Accurate Measure of Ca2+ Transients - Does it Matter?
Co-chairs: Ana Maria Gomez, INSERM, France
                     Josine deWinter, Amsterdam UMC, The Netherlands

13:00 - 13:20 
Ana Maria Gomez, INSERM, France
CA2+ Dynamics in Cardiac Pathological Models

13:20 - 13:40 
Josine deWinter, Amsterdam UMC, The Netherlands
KBTBD13 is a Novel Cardiomyopathy Gene

13:40 - 14:00 
Corrado Poggesi, University of Florence, Italy
Excitation-Contraction Coupling Alterations in Hypertrophic Cardiomyopathy and Arrhythmia Propensity

14:00 - 14:20 
Leonardo Sacconi, European Laboratory for Non-Linear Spectroscopy, Italy
Correlating Electrical Disfunction and Structural Remodeling in Arrhythmogenic Mouse Hearts by Advanced
Optical Methods

14:20 - 14:30
Sage Malingen, University of Washington, USA*
Molecular Dynamics Simulations Reveal Functional Changes in Troponin Resulting From Mutations Implicated in Cardiomyopathies

14:30 - 15:00 | Coffee Break

Session IV: What's New in Thin Filament Regulation and What Cryo-EM Doesn't Tell Us
Co-chairs:  Jil Tardiff, The University of Arizona, USA
                    Ivanka Sevrieva, Kings College London, United Kingdom

15:00 - 15:20 
Jil Tardiff, The University of Arizona, USA
Walking a Thin (Filament) Line: Integrating Time-Resolved Fret and Computation to Identify Novel Pathogenic
Mechanisms in Hypertrophic Cardiomyopathy

15:20 - 15:40 
Ivanka Sevrieva, Kings College London, United Kingdom
Comparison of the Cardiac Troponin Conformation Determined by Polarized Fluorescence AD CRYO-EM

15:40 - 16:00 
William Lehman, Boston University, USA
TROPONIN-I Induced Tropomyosin Pivoting Defines Cardiac Thin Filament Structure in Relaxed Muscle

16:00 - 16:20
Yuichiro Maeda, Okayama University, Japan
Structures and Mechanisms of Actin ATP Hydrolysis

16:20 - 16:30
Joseph Chalovich, ECU Brody School of Medicine, USA*
The Unstructured C-Terminal Region of Troponin T Retards Calcium Activation of Striated Muscle

16:30 - 18:00
Poster Session I

18:00 - 18:45
Keynote Address | Steven Schwartz, The University of Arizona, USA
Model Building Challenges and the Time-Scale Problem in the Computational Study of Muscle Biophysics


Tuesday, July 18, 2023

8:15 - 14:45

8:15 - 9:00
Keynote Address | Leslie Leinwand, University of Colorado, USA
Multiscale Regulation of Sarcomeres in Health and Disease

Session V: What do Modelers Need from Experimentalists and Vice Versa? 
Chair: Malcolm Irving, Kings College London, United Kingdom

9:00 - 9:15
Stuart Campbell, Yale University, USA
Predicting Clinical Phenotypes of TPM1 Missense Mutations

9:15 - 9:30
Martin Pfaller, Stanford University, USA
FSGE: A Computational Model for Equilibrated Cardiovascular Fluid-Solid-Growth Interaction

9:30 - 10:30
Panel Discussion
Chair: Malcolm Irving, King's College London, United Kingdom

10:30 - 10:45 | Coffee Break

Session VI: Small Molecule Therapeutics for Muscle Disease
Chair: Michael Regnier, University of Washington, USA 

10:30 - 10:50
Michael Regnier, University of Washington, USA
Experimental and Computational Approaches for Mechanistic Analysis and Therapeutic Development
of 2-Deoxy ATP to Treat Heart Failure

10:50 - 11:10
Allan Russell, Edgewise Therapeutics, USA
Modulating Fast Skeletal Muscle Contraction as a Novel Strategy for the Protection of Skeletal Muscle
in Muscular Dystrophy

11:10 - 11:30
James Hartman, Cytokinetics, USA
Preclinical Characterization of CK-4021586, A New Class of Cardiac Myosin Inhibitors for the Treatment of
Hypertrophic Cardiomyopathy

11:30 - 11:50
Andras Malnasi-Csizmadia, Eötvös Loránd University, Hungary
Drug Design Targeting Myosin Blebbistatin Binding Site

11:50 - 12:00
Marcus Hock, University of California, San Diego, USA*
Multiscale Simulations of the Effects of 2'-Deoxy-ATP and Myosin Mutations on Actomyosin Interactions

12:15 - 13:15 | Lunch Break

13:15 - 14:45
Poster Session II

Wednesday, July 19, 2023

8:15 - 18:00

8:15 - 8:45
Keynote Address | Elisabetta Brunello, King’s College of London, United Kingdom
Structural Dynamics of the Thick Filament During the Physiological Cardiac Cycle

Session VII: What's New in Thick Filament Regulation
Co-chairs: Samantha Harris, The University of Arizona, USA
                     Christopher Toepfer, University of Oxford, United Kingdom

8:45 - 9:05
Samantha Harris, The University of Arizona, USA
Cut and Paste of Myosin Binding Protein-C in Skeletal Muscles

9:05 - 9:25
Christopher Toepfer, University of Oxford, United Kingdom
Understanding Hypertrophic Cardiomyopathy (Hcm) Across the Thick and Thin Filament, Bridging In-Vitro and
In-Silico Models of Disease to Accelerate Pathomechanism Discovery

9:25 - 9:45
Thomas Irving, Illinois Institute of Technology, USA
Myosin Based Regulation: The Plot Thickens

9:45 - 10:05
Neil Kad, University of Kent, United Kingdom
Single Molecule Imaging Approaches Towards Understanding Dual Filament Regulation in Muscle

10:05 - 10:15
Charles Chung, Wayne State University, USA*
Ramp-Stretches During Relaxation of Twitching Intact Cardiac Traecula Suggest a Need for Dynamic Models of
Myofilament Function

10:15 - 10:45 | Coffee Break

Session VIII: Cross-Bridge Recruitment and Dynamics: New and Unresolved Questions
Co-chairs: Michael Geeves, University of Kent, United Kingdom
                     Mamta Amrute-Nayak, Medical School of Hanover, Germany

10:45 - 11:05
Michael Geeves, University of Kent, United Kingdom
Are the DRX and SRX Sates in Thermal Equilibrium a Paradox?

11:05 - 11:25
Mamta Amrute-Nayak, Medical School of Hanover, Germany
Evidence for Two Distinct Actomyosin Cross-Bridge Stiffness for Human Beta Cardiac Myosin

11:25 - 11:45
David Warshaw, University of Vermont, USA
Myosin-Binding Protein C/H: Impact on Muscle Contractility and Development

11:45 - 12:05
Edward Debold, University of Massachusetts, USA
Recent Biophysical Approaches to Investigate the Coupling Between Force-Generation and
Phosphate-Release in Myosin

12:05 - 12:15
Matvey Pilagov, University of Kent, United Kingdom*
Super-Resolution Single-Molecule Imaging of ATP Usage in Myofibrils to Study Thick Filament Regulation

12:15 - 13:15 | Lunch Break

Session IX: What is on the Horizon from Modellers and Experimentalists?
Chair: Andrew McCulloch, University California, San Diego, USA

13:15 - 13:30
Andrew McCulloch, University of California, San Diego, USA
Multi-scale Modeling of Muscle Biophysics: From Molecules to Populations

13:30 - 13:45
Farah Sheikh, University of California, San Diego, USA
CONNEXIN43 Restoration Alleviates End-Stage Alterations in Arrhythmogenic Right Ventricular

13:45 - 14:30
Panel Discussion
Andrew McCulloch, University of California, San Diego

14:30 - 15:00 | Coffee Break

Session X: Passive Tension in Muscle Cells: Protein Players and Plasticity
Co-chairs: Jolanda van der Veldon, Amsterdam University, The Netherlands
                     Matthew Caporizzo, University of Vermont, USA

15:00 - 15:20
Jolanda van der Veldon, Amsterdam University
Modulators of Cardiac Muscle Relaxation, and their Role in Cardiac Pathology

15:20 - 15:40
Matthew Caporizzo, University of Vermont, USA
Microtubules are Viscous Regulators of Myocardial Motion

15:40 - 16:00
Michael Gotthardt, Max Delbruck Center, Germany
Regulating Titin Based Stiffness in Health and Disease

16:00 - 16:20
Jennifer Davis, University of Washington, USA
Fibroblast-Mediated Regulation of Cardiac Structure and Stiffness

16:20 - 16:30
Bradley Palmer, University of Vermont, USA*
Contribution of Thick Filament Stiffness to Length Dependent Activation in Cardiac Muscle

16:30 - 18:00
Poster Session III

Dinner Banquet

Thursday, July 20, 2023

8:15 - 12:45

8:15 - 8:45
Keynote Address | Thomas Daniel, University of Washington, USA
Multiscale Models of Muscle Melding Molecular and Myofilament Levels of Organization

Session XI: Sarcomere and Muscle Cell Models of Contractile Dynamics
Co-chairs: Kenneth Campbell, University of Kentucky, USA
                     Cheavar Blair, University of California, Santa Barbara, USA

8:45 - 9:05
Kenneth Campbell, University of Kentucky, USA
Multiscale Modeling of Pathological Cardiac Growth

9:05 - 9:25
Cheavar Blair, University of California Santa Barbara, USA
Sarcomere Dynamics Simulation to Uncover Mechanisms in Hypertrophic Cardiomyopathy

9:25 - 9:45
Michael Greenberg, Washington University in St. Louis, USA
Harnessing Multiscale Models to Understand Dilated Cardiomyopathy Thin Filament Mutations

9:45 - 10:05
Farid Moussavi-Harami, University of Washington, USA
Machine Learning for Building Classifiers and Rate Estimates in Simulated Twitches

10:05 - 10:15
Howard White, Eastern Virginia Medical Center Physiological Sciences, USA*
Structure of Prepowerstroke Actomyosin by Cryoelectronmicroscopy at 10 MS and 5A

10:15 - 10:45 | Coffee Break

Session XII: Upscale Modeling: Myofilaments to Movement
Co-chairs: Silvia Blemker, University of Virginia, USA
                     Kiisa Nishikawa Northern Arizona University, USA

10:45 - 11:05
Silvia Blemker, University of Virginia, USA
Multi-Scale Modeling Across Muscles, Contexts, and Diseases

11:05 - 11:25
Kiisa Nishikawa, Northern Arizona University, USA
Multiscale Muscle Modeling: An Organismal Approach

11:25 - 11:45
Madhusudhan Venkadesan, Yale University, USA
Emergent Rheology of Actomyosin Ensembles

11:45 - 12:05
Anne Silverman, Colorado School of Mines, USA
Modeling Muscle Coordination in Whole Body Movement

12:05 - 12:15
Bertrand Tanner, Washington State University, USA*
An Experimental Approach to Manipulate the Multi-Scale Components of Whole-Body Movement
That Influence Single Muscle Fiber Work and Power Output

12:15 - 12:45
Closing Remarks and Biophysical Journal Poster Awards

*Selected Short Talks