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Drug Discovery: From worms to fish to mice

  1. Guy M Benian  Is a corresponding author
  2. Hyojung J Choo
  1. Department of Pathology, Emory University, United States
  2. Department of Cell Biology, Emory University, United States
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Cite this article as: eLife 2020;9:e57481 doi: 10.7554/eLife.57481
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Muscle contraction and a 'multi-species discovery pipeline' for drug screening.

(A) Ryanodine receptor 1 (RyR1; blue) is a channel protein that releases calcium ions (yellow) from the sarcoplasmic reticulum (SR) when activated by a dihydropyridine receptor (DHP; green). Muscle tissue contains thick filaments (blue) and thin filaments (orange) arranged in units called sarcomeres. The calcium ions cause structures on the thick filaments called myosin heads (not shown) to bind to the thin filaments and pull them so that the muscle contracts. The DHP receptor is activated by action potentials (red spikes) travelling along a structure called a T-tubule (blue). (B) Drug screening was performed sequentially using null mutants in C. elegans (top), zebrafish (middle), and mouse myotubes (bottom). A screen of 3700 compounds in C. elegans identified 74 compounds that enabled the mutants to grow. Testing many of these 74 compounds on zebrafish revealed two compounds that improved the swimming performance of the mutant animals. Both compounds were known to be inhibitors of a protein kinase called p38, and both were found to induce the release of calcium ions in mutant mouse muscle cells.

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