You may remember during the first lockdown of 2020; social media platforms blew up with images and videos of bioluminescence lighting up the Southern Californian coast at night. Surfers took to surfing glowing waves in the evening and it made for some great media content to keep people busy during lockdown. But what is bioluminescence? And how is it being harnessed to develop lifesaving technology in medicine? Today bioluminescence is being used for a wide variety of innovations, from lighting up structures inside the brain to illuminating the progression of cancer cells.
There is evidence that as far back as 500 BCE, sailors have been writing about luminous and sparkling seas in the darkness [1]. Bioluminescence is an amazing phenomenon that happens when the emission of light by living organisms takes place [2]. The release of light is caused by the oxidation of a small organic molecule called luciferin, which is catalysed by the enzyme luciferase [2].
A vast range of in vitro and in vivo analytical techniques have been developed using bioluminescent proteins [2]. Some of these include immunoassays, gene expression assays, drug screening, cancer studies, bioimaging of live organisms, and the investigation of infectious diseases and environmental monitoring [2]. Green fluorescent protein from the crystal jellyfish Aequorea Victoria amongst other fluorescent proteins has revolutionised research fields from neuroscience to immunology [3]. Neurobiologist Vincent Pieribone from the Yale University School of Medicine has said these proteins are allowing researchers to do what was once considered science fiction: understand, manipulate, and even interact with the living brain [3]. For many years it was thought that green was the most reliable fluorescence colour for live brain imaging [3]. However, a new fluorescent protein has been identified which allows live neurons to glow red once they have been activated [3, 4]. The new protein, voltage-activated neuronal activity monitor (VARNAM), changes its fluorescence intensity as an electrical impulse moves through a live neuron and its discovery is a significant advancement in our ability to monitor the electrical activities of brain cells less invasively and more comprehensively [4].
Bioluminescence has also contributed to the development of cancer immunotherapies. Previously the gold standard to evaluate whether an immunotherapy was working was a complicated and expensive radioactive chromium release assay [3]. However, researchers at the University of Southern California’s Keck School of Medicine have developed a more accurate assay using luciferase, named the Matador assay. Bioluminescent Pacific Ocean crustaceans were used to develop this test of immunotherapy, and the assay has been named after the El Matador State Beach in Malibu, California. It works by first introducing luciferase into cancer cells, the enzyme then leaks out as the cells die, leaving behind a visible glow that is measured. More specifically, luciferase is used to measure the expression of chimeric antigen receptors on the surface of a patient’s disease-fighting T cells. The assay has been tested in multiple cancers including chronic myelogenous leukaemia, acute myelogenous leukaemia, and Burkitt lymphoma. The Matador assay can detect cell death in 30 minutes which will enable faster treatments for patients receiving immunotherapies like CAR-T cells, says Preet Chaudhary, one of the senior researchers.
So, there you have it, not only does luciferase produce one of the most amazing natural phenomena that take place in our oceans, but this enzyme is also being harnessed to change the future of brain imaging methodologies and the way immunotherapies are assessed. In addition, Bioluminescence is also being used to develop; novel, more comprehensive bioimaging sensors to characterise cell signalling pathways and aid in drug development, new photodynamic immunotherapies from firefly-light based on the bioluminescence activated destruction of cancer to reach even the deepest lying cancers, and lastly, a newly discovered form of luciferin may have the potential to monitor cancer cells and identify infectious diseases. Bioluminescence is clearly making waves in biomedical science and we cannot wait to see what else is possible from harnessing this beautiful source of natural light.
Mia Georgiou
Bibliography:
[1] Rosenfeld, J., 2016. 7 Ways Bioluminescence Has Revolutionized Medical Research. [online] Mentalfloss.com. Available at: <https://www.mentalfloss.com/article/80813/7-ways-bioluminescence-has-revolutionized-medical-research> [Accessed 14 January 2021].
[2] Kaskova, Z., Tsarkova, A. and Yampolsky, I., 2016. 1001 lights: luciferins, luciferases, their mechanisms of action and applications in chemical analysis, biology and medicine. Chemical Society Reviews, 45(21), pp.6048-6077.
[3] Cheryl Lyn Dybas, Illuminating New Biomedical Discoveries: Bioluminescent, biofluorescent species glow with promise, BioScience, Volume 69, Issue 7, July 2019, Pages 487–495, https://doi.org/10.1093/biosci/biz052
[4] Kannan, M., Vasan, G., Huang, C. et al. Fast, in vivo voltage imaging using a red fluorescent indicator. Nat Methods 15, 1108–1116 (2018). https://doi.org/10.1038/s41592-018-0188-7
[5] Matta, H., Gopalakrishnan, R., Choi, S., Prakash, R., Natarajan, V., Prins, R., Gong, S., Chitnis, S., Kahn, M., Han, X., Chaudhary, V., Soni, A., Sernas, J., Khan, P., Wang, D. and Chaudhary, P., 2018. Development and characterization of a novel luciferase-based cytotoxicity assay. Scientific Reports, 8(1).
