Ran Zalk, PhD

   My goal is to design biochemistry experiments to obtain results that can be structurally and functionally interpreted using Cryo-EM and crystallography tools. This way I aim to obtain important insight into the molecular-level regulatory processes such as the control of RyR1 channel activity by post-transnational modifications, which are major regulatory modulators of skeletal and cardiac muscle contraction.

   This has also therapeutic implication. Under conditions of chronic stress, including heart failure and muscular dystrophy, ryanodine receptor/calcium release channels become “leaky” as a result of post-translational modifications such as phosphorylation and oxidation and nitrosylation.  This intracellular calcium leak can drive progressive heart failure, trigger fatal cardiac arrhythmias, and promote muscle damage and decrease exercise capacity in muscular dystrophy animal models. Thus, gaining new understandings of how the RyR/calcium release channels are regulated, and how drugs that fix the calcium leak bind to the channels has important implications for developing novel therapies for heart and skeletal muscle diseases.