Sarah and Sam present their work at the Biophysical Society Annual Meeting
Sarah Clippinger had a talk and Sam Barrick presented a poster at the Biophysical Society Annual Meeting in Baltimore.
New preprint from the Greenberg Lab – Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy
https://www.biorxiv.org/content/10.1101/555391v1 Sarah R Clippinger, Paige E Cloonan, Lina Greenberg, Melanie Ernst, W. Tom Stump, Michael J Greenberg Familial dilated cardiomyopathy (DCM) is a leading cause of sudden cardiac death and a major indicator for heart transplant. The disease is frequently caused by mutations of sarcomeric proteins; however, it is not well understood how these molecular mutations lead to alterations in cellular organization and contractility. To address this critical gap in our knowledge, we studied the molecular and cellular consequences of a DCM mutation in troponin-T, ΔK210. We determined the molecular mechanism of ΔK210 and used computational modeling to predict that the mutation should reduce the force per sarcomere. In mutant cardiomyocytes, we found that ΔK210 not only reduces contractility, but also causes cellular hypertrophy and impairs cardiomyocytes ability to adapt to changes in substrate stiffness (e.g., heart tissue fibrosis that occurs…
New preprint from the Greenberg Lab – Computational tool to study perturbations in muscle regulation and its application to heart disease
https://www.biorxiv.org/content/10.1101/548404v3 Samantha K Barrick, Sarah R Clippinger, Lina Greenberg, Michael J Greenberg Striated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., β-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the mechanism of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work…
Michael presents lab data at Duke
Michael presented the lab's work at Duke for the Computational Biology and Bioinformatics program.
Sarah and Sam present their data at the Gibbs Conference
Sarah Clippinger and Sam Barrick presented their data at the Gibbs Conference on Biothermodynamics.
Sarah is recognized with the Elliot L. Elson Education and Training Award
Congratulations to Sarah Clippinger for being recognized with the Elliot L. Elson Education and Training Award! This award supports educational opportunities for outstanding students and post-doctoral trainees in the Department of Biochemistry and Molecular Biophysics. More information about the award can be found here.
Michael has a new publication dissecting the mechanism of a heart failure drug
Michael has a new publication that was recently accepted to Nature Communications entitled, "Positive Cardiac Inotrope, Omecamtiv Mecarbil, Activates Muscle Despite Suppressing the Myosin Working Stroke". This work was done with the labs of Yale Goldman, Don Winkelmann, and Mike Ostap. The preprint can be found here. The publication can be found here.
The Greenberg lab has a new publication on engineering models of heart failure
The Greenberg lab, in collaboration with the Wakatsuki lab, has a new publication in Frontiers in Cardiovascular Medicine entitled, "Genetic and Tissue Engineering Approaches to Modeling the Mechanics of Human Heart Failure for Drug Discovery". See the paper here.