Florescence Calcium Sensors

To meet the pressing demand for probing calcium signaling with rapid dynamics, we have designed Ca2+ sensors (CatchERs, Calcium sensor for detecting high concentration in the ER) with the fastest kinetics. The developed sensors have been widely applied to monitor >100 cellular signaling events in real time and identify novel drugs against specific pathways under physiological and pathological conditions. They have strong capabilities in probing calcium dynamics, signaling and disease states in high calcium concentration environment with enhancement in both fluorescence and lifetime. CatchER enables us to monitor SR luminal Ca2+ in flexor digitorum brevis (FDB) muscle fibers to determine the mechanism of diminished SR Ca2+ release in aging mice for molecular imaging. Using CatchER, we observed that young and old mice have similar resting ER Ca2+ concentrations, while Ca2+ release significantly decreases in aging mice. CatchER enabled this first direct demonstration that impaired ER Ca2+ release occurs in the absence of significant changes in ER Ca2+ content with aging. Our Ca2+ sensors enable us to effectively elucidate the influence of luminal proteins on ER Ca2+ dynamics directly and are sensitive enough to detect differences in ER Ca2+ concentration between various cell types and physiological and pathological states. As a genetically encoded calcium indicator with lifetime changes, CatchER allows long-term observation and high targeting specificity and provides further opportunities for tagging multiple channels in the membrane with minimal perturbation. It will potentially elucidate novel signaling pathways and disease mechanisms by monitoring the activity of targeted receptors or channels with high specificity and precision.

Publications

  • 1) Shen Tang, Hing-Chueng Wong, Zhong-Min Wang, Yun Huang, Jin Zou, Andreas Pennati, Giovanni Gadda, Osvaldo Delbono, Jenny J. Yang Proc Natl Acad Sci U S A (2011). Sep 27; 108(39):16265-70. PMID: 21914846.
  • 2) Zhong-Min Wang, Shen Tang; Maria Messi, Jenny J. Yang, Osvaldo Delbono. Pflugers Archiv-European Journal of Physiology (2011). 463(4):615-24 [Epub ahead of print] PMID: 22249494.
  • 3) You Zhuo, Kyril M. Solntsev, Florence Reddish, Shen Tang, and Jenny J. Yang. Journal of Physical Chemistry B (2014). Jun 5. [Epub ahead of print] PMID: 24836743
  • 4) (45). Jin Zou, Aldebaran M. Hofer, Monica Lurtz, Giovanni Gadda, April L. Ellis, Ning Chen, Yun Huang, Angela Holder, Yiming Ye, Charles Louis, Kristy Welshhans, Biochemistry 2007 Oct 9; [Epub ahead of print]. Oct 30; 46(43):12275-88. PMID: 17924653.

Patents

  • Patent No.: 9,151,767; 2015-10-06, Issued
  • Patent No.: EP 1784753; 2013-03-20, Issued
  • Patent No.: US8,420,327B2; 2013-04-16, Issued
  • Patent No.: US9,201,012B2; 2015-12-01, Issued
  • Patent No.: EP2097507B1; 2015-05-06, Issued
  • Patent No.: US8.865,416B2; 2014-10-21, Issued
  • Patent No.: WO2012/054648 A2; 2012-04-26, Application
  • Patent No.: WO 2008/076365 A2; 2008-06-26, Application
  • Patent No.: WO2015021143 A1; 2015-02-12, Application
  • Patent No.: WO 2006/020550 A2; 2006-02-23, Application
  • Apps in US (con.), AU, CA, CN, EP & JP