It is summer time again and nature’s little tea lights-the fireflies- can be spotted everywhere. Many of us have fond memories of collecting them in a jar to make a lantern and awing at their glow.
Bioluminescent organisms produce light as a result of a reaction of a specific chemical with oxygen in the presence of a dedicated molecular catalyst, or enzyme. A vast variety of organisms exhibit this phenomenon, including insects, flies, fungi, snails, worms, and even microorganisms like dinoflagellates and bacteria. While many of these organisms can be found on land, most live in the ocean, where in the deep, dark waters, a little light can take them quite far. These incredible animals use their light to attract mates, communicate danger or other signals to their kin, startle, intimidate, and even fight predators.
Through decades of research on this fascinating phenomenon, scientists have achieved an impressive understanding of the key players involved in the production of light in a variety of bioluminescent organisms. The generated knowledge is now being applied to solve rather complex challenges facing biomedical research aimed at drug discovery as well as the development and treatment of cancer.
The application is called bioluminescence imaging (BLI), and is based on a simple idea: Use recombinant DNA technology to produce target cells expressing bioluminescence-effecting enzymes, provide the chemical substrate, and track target cells in a live animal by imaging the production of light.
The uses of this non-invasive technology are innumerable. For example, human brain tumor cells can be genetically modified to express firefly luciferase, the enzyme responsible for catalyzing the production of light by luciferin (the chemical), transplanted into mice brain, and visualized using a specialized camera upon deliverance of luciferin. The resulting light signals the presence of tumor cells. Using this study design, scientists can assess the effect of various chemotherapy drugs on the size of the tumor, and determine parameters such as dosage and efficacy of the drugs, and the time a particular drug takes to stall a neoplastic growth.
BLI is also tackling metastasis, or the spread of cancer from one part of the body to the other. Luciferase-expressing tumor cells can be injected in the tail veins of mice and their migration tracked by following the emission of light from the body of the mice. Another exciting avenue is exploiting the ability of bacteria to preferentially colonize tumor cells by injecting specially engineered bioluminescent bacteria into mice models of cancer to track the presence of cancerous lesions in the mice. Scientists hope that these bacteria can be engineered to serve as targeted drug delivery vehicles to the site of cancer lesions, to prevent damage to bystander cells, as is often the side-effect of chemotherapy. Other areas of application include “cell signaling, transcriptional promoters, gene expression, protein-protein interactions” and many more.
As with any technology, BLI has its limitations and drawbacks. Thus, efforts are being made every day to improve the technology by engineering enzymes with longer half-lives and better stability, more sensitive detection methods, and efficient experimentation techniques.
One of the basic challenges with biomedical research is differentiating a cell or tissue of interest from the rest. Visualization offers a viable solution. Being able to differentially visualize the cell or tissue of interest can allow one to make targeted interventions. It’s like walking in a room and having a specific switch to only turn on the light of a lamp in one of the many rooms with many lamps of a mansion- a complex task, simplified elegantly by the promise of BLI.
Badr CE. Bioluminescence Imaging: Basics and Practical Limitations. Methods Mol Biol. 2014;1098:1-18
Haddock, S.H.D.; McDougall, C.M.; Case, J.F. “The Bioluminescence Web Page”, http://lifesci.ucsb.edu/~biolum/ (created 1997; updated 2011; accessed 06/27/14).