Date(s) - 09/13/2010
5:00 pm - 6:00 pm
Engineers and physiologists are alike in that they both are interested in trying to understand and control the function of complex physical/biological systems. Quantitative characterizations are essential for this purpose. Phenomenological or “black-box” approaches are frequently used to develop these characterizations (or models), especially in the biological world where modeling based on first principles (ab intio modeling) is often not possible. The utility of these phenomenological models is significantly increased if they possess predictive (i.e., prediction of system function under circumstances other than those used to construct the model) and interpretive (i.e., connection between model parameters and underlying physical/biological processes) abilities. Although our research efforts are in both cardiac and vascular systems, this presentation is limited to the cardiac system only. Specifically, three examples will be discussed to illustrate the point that quantitative analyses coupled with novel experiments can be a powerful tool to address both basic biological questions and clinical problems: (1) Contractile proteins (myosin isoenzyme composition) and left ventricular (LV) mechanical function under normal and pathological conditions (e.g., hypertensive hypertrophy and transition from compensated stage of hypertrophy to heart failure); (2) Phosphorylation of regulatory proteins (especially, troponin I) and LV mechanical function, with an emphasis on developing novel forms of inotropic therapy using molecular perturbations; and (3) Myofilament acetylation-mediated regulation of cardiac muscle contraction.