CaBLAM: a high-contrast bioluminescent Ca2+ indicator derived from an engineered Oplophorus gracilirostris luciferase. Lambert, G. G., Crespo, E. L., Murphy, J., Turner, K. L., Gershowitz, E., Cunningham, M., Boassa, D., Luong, S., Celinskis, D., Allen, J. J., Venn, S., Zhu, Y., Karadas, M., Chen, J., Marisca, R., Gelnaw, H., Nguyen, D. K., Hu, J., Sprecher, B. N., Tree, M. O., Orcutt, R., Heydari, D., Bell, A. B., Torreblanca-Zanca, A., Hakimi, A., Czopka, T., Shoham, S., Nagel, K. I., Schoppik, D., Andrade, A., Lipscombe, D., Moore, C. I., Hochgeschwender, U., & Shaner, N. C. Nature Methods, 23(1):205–215, January, 2026.
CaBLAM: a high-contrast bioluminescent Ca2+ indicator derived from an engineered Oplophorus gracilirostris luciferase [link]Paper  doi  abstract   bibtex   
Abstract Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM (‘calcium bioluminescence activity monitor’), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.
@article{lambert_cablam_2026,
	title = {{CaBLAM}: a high-contrast bioluminescent {Ca2}+ indicator derived from an engineered {Oplophorus} gracilirostris luciferase},
	volume = {23},
	issn = {1548-7091, 1548-7105},
	shorttitle = {{CaBLAM}},
	url = {https://www.nature.com/articles/s41592-025-02972-0},
	doi = {10.1038/s41592-025-02972-0},
	abstract = {Abstract
            Monitoring intracellular calcium is central to understanding cell signaling across nearly all cell types and organisms. Fluorescent genetically encoded calcium indicators (GECIs) remain the standard tools for in vivo calcium imaging, but require intense excitation light, leading to photobleaching, background autofluorescence and phototoxicity. Bioluminescent GECIs, which generate light enzymatically, eliminate these artifacts but have been constrained by low dynamic range and suboptimal calcium affinities. Here we show that CaBLAM (‘calcium bioluminescence activity monitor’), an engineered bioluminescent calcium indicator, achieves an order-of-magnitude improvement in signal contrast and a tunable affinity matched to physiological cytosolic calcium. CaBLAM enables single-cell and subcellular activity imaging at video frame rates in cultured neurons and sustained imaging over hours in awake, behaving animals. These capabilities establish CaBLAM as a robust and general alternative to fluorescent GECIs, extending calcium imaging to regimes where excitation light is undesirable or infeasible.},
	language = {en},
	number = {1},
	urldate = {2026-09-09},
	journal = {Nature Methods},
	author = {Lambert, Gerard G. and Crespo, Emmanuel L. and Murphy, Jeremy and Turner, Kevin L. and Gershowitz, Emily and Cunningham, Michaela and Boassa, Daniela and Luong, Selena and Celinskis, Dmitrijs and Allen, Justine J. and Venn, Stephanie and Zhu, Yunlu and Karadas, Mürsel and Chen, Jiakun and Marisca, Roberta and Gelnaw, Hannah and Nguyen, Daniel K. and Hu, Junru and Sprecher, Brittany N. and Tree, Maya O. and Orcutt, Richard and Heydari, Daniel and Bell, Aidan B. and Torreblanca-Zanca, Albertina and Hakimi, Ali and Czopka, Tim and Shoham, Shy and Nagel, Katherine I. and Schoppik, David and Andrade, Arturo and Lipscombe, Diane and Moore, Christopher I. and Hochgeschwender, Ute and Shaner, Nathan C.},
	month = jan,
	year = {2026},
	pages = {205--215},
	file = {Full Text PDF:/Users/justineallen/Zotero/storage/MPLJD388/Lambert et al. - 2026 - CaBLAM a high-contrast bioluminescent Ca2+ indicator derived from an engineered Oplophorus gracilir.pdf:application/pdf},
}

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