In the project, the Virtual Cell will be used to predict a cell's response of the association between FKBP and the rvanodine receptor in calcium signaling (Barbara E. Ehrlich, Yale University, NIH funded): In the project, the Virtual Cell will be used to predict a cell's response to changes in the interaction between FKBP and the ryanodine receptor (RyR). In single channel experiments it is possible to replace the FKBP with a different isoform and/or mutant FKBP, but the same experiment in an intact cell is quite difficult. The experimentally derived single channel behavior and cellular response predicted by the Virtual Cell will allow them to select the appropriate avenues for investigation. FKBP and its homologs have been shown to modulate the gating of RyR. The hypothesis to be studied here is that removal of FKBP from lipid bilayer preparations of RyR will allow the RyR to open at lower Ca2+. The basic data will be collected in the laboratory of the applicant by patch clamp record ing. The Resource will provide imaging data to show in intact cardiac and skeletal muscle cells, the distribution of SR and RyR. These data, in combination with patch clamp results, will be fed into the Virtual Cell to predict the role of FKBP on RyR activity in intact cells. 13816-01A1
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