In 1954 he began a long collaboration with Beatrice M. Sweeney, who was then at the Scripps Institution of Oceanography, in elucidating the cellular and biochemical mechanisms of luminescence in the unicellular dinoflagellate Lingulodinium polyedrum (formerly known as Gonyaulax polyedra).

Once the concentration of this substance reaches a critical level (a measure of the number of bacteria in a limited area), transcription of specific other genes that had been repressed are turned on.

They elucidated the structures of the luciferins and luciferases,[17] the organization and regulation of their associated genes, temporal control mechanisms,[18] and the actual sub-cellular identity and location of the light emitting elements, which they termed scintillons.

[19] They demonstrated that the reaction is controlled by a drop in pH when an action potential leads to the entry of protons via voltage-activated membrane channels in the scintillons.

[20] Through immunolocalization studies the Hastings lab showed that scintillons are small peripheral vesicles (0.4 μm) that contain both the luciferase and the luciferin-binding protein.

[21] More recently, the lab found that the luciferase gene in Lingulodinium polyedrum and other closely related species contains three homologous and contiguous repeated sequences in a kind of "three-ring circus with the same act in all three.

[29] In other work when he was in the McElroy lab he examined the basic biochemical mechanism of firefly luciferase and demonstrated that coenzyme A stimulates light emission.

[9] Once characterized and cloned, GFP has become a crucial molecule used as a reporter and tagging tool for studying gene activation and developmental patterns.

[10] Osamu Shimomura, Martin Chalfie and Roger Tsien received the Nobel Prize in Chemistry in 2008 for their work on this remarkable molecule.