Development of novel myofilament-specific indicators for Ca2+ and protein mobility

We set out to design and target genetically encoded calcium sensors to the contractile apparatus of a living cardiomyocyte for the first time. To this end, we have used our Oxford BHF CRE pump-priming award to design, deliver and test this novel reagent in both human IPSc and guinea pig adult cardiac cells. In short, these experiments were successful and the molecular tool has given detailed mechanistic information on multiple drug screens and the effect of cardiomyopathy causing mutations on myofilament calcium handling. 

Publication linked to this award:

1. Robinson, P., Liu, X., Sparrow, A., Patel, S., Zhang, Y., Casadei, B., Watkins, H. and Redwood, C. (2018). Hypertrophic cardiomyopathy mutations increase myofilament Ca2+buffering, alter intracellular Ca2+handling, and stimulate Ca2+-dependent signaling. Journal of Biological Chemistry, 293(27), pp.10487-10499.

2. Robinson, P., Sparrow, A., Broyles, C., Sievert, K., Chang, Y., Brook, F., Zhang, X., Watkins, H., Abassi, Y., Geeves, M., Redwood, C. and Daniels, M. (2018). Measurement of myofilament calcium in living cardiomyocytes using a targeted genetically encoded indicator. doi: 10.1101/268003.