With bioluminescence imaging techniques, as with emotions, it can be difficult to look beyond the surface and see what’s going on deep inside. Inspired by fireflies, this imaging method makes use of green-yellow light emitted when an enzyme called luciferase reacts with d-luciferin. Light of this wavelength doesn’t travel far through tissue, which has limited the technique’s depth of visualization. Now, researchers in Japan have engineered a synthetic bioluminescence system that emits red-shifted light that is up to 1,000 times as bright as light emitted by existing systems and can penetrate through the deep tissue of mice and marmosets (Science 2018, DOI: 10.1126/science.aaq1067). The researchers installed their new imaging system in the animals’ striatum, an area deep in the brain, in two steps. First, they injected a virus containing their improved luciferase, an enzyme called Akaluc discovered through directed evolution. Then they fed the animals or injected them with a synthetic luciferin compound called AkaLumine-HCl, which is better able to penetrate the blood-brain barrier than d-luciferin is. As the enzyme reacted with AkaLumine-HCl, they observed the bioluminescence using a special camera. This system’s increased brightness lets scientists circumvent the longer exposure times previously required, allowing them to study the animals while they move freely, instead of under anesthesia, which is important for understanding brain activity.