Luminescence is one of the most powerful technologies for imaging the processes and structures within a cell or organism. By using a light-emitting luciferin along with a luciferase catalyst, researchers can cause cells to emit light under the appropriate conditions. For example, tumors can be made to light up and reveal their extent and location, or pathogens can be caused to glow. Presently, however, it is only possible to insert the genes for the luciferase component of this system. Luciferin, the small molecule which emits the light, has to be industrially synthesized and then added by injection or perfusion. One of the most widely used light-emitters in reporting systems is the luciferin called coelenterazine, which is naturally produced by some marine invertebrates. The genes responsible for its production have never been identified. The goal of this research is to characterize and isolate the coelenterazine luciferin biosynthesis pathway and develop it as a powerful new reporter system for luminescent imaging of cellular processes. Successful completion of this project would enable a wide range of new approaches to cellular and molecular imaging, since it would allow modified cells to become self-luminous. This is a high-risk/high-benefit research project, but its eventual success will enable a powerful new generation of molecular reporter capabilities.

Public Health Relevance

Research Narrative: This project will provide a powerful new tool for molecular, cellular, and diagnostic imaging by allowing researchers to light up whatever cells they are interested in. Adding a bit of DNA to a cell will give it the ability to make its own luminescence. The possible applications are nearly limitless, but include making tumors reveal themselves by glowing, detecting contamination by causing pathogens to emit light, and following the time course of gene expression in organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM087198-04
Application #
8296563
Study Section
Microscopic Imaging Study Section (MI)
Program Officer
Deatherage, James F
Project Start
2009-06-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$323,836
Indirect Cost
$82,441
Name
Monterey Bay Aquarium Research Institute
Department
Type
DUNS #
178341772
City
Moss Landing
State
CA
Country
United States
Zip Code
95039
Francis, Warren R; Powers, Meghan L; Haddock, Steven H D (2014) Characterization of an anthraquinone fluor from the bioluminescent, pelagic polychaete Tomopteris. Luminescence 29:1135-40
Powers, Meghan L; McDermott, Amy G; Shaner, Nathan C et al. (2013) Expression and characterization of the calcium-activated photoprotein from the ctenophore Bathocyroe fosteri: insights into light-sensitive photoproteins. Biochem Biophys Res Commun 431:360-6
Chudakov, Dmitriy M; Matz, Mikhail V; Lukyanov, Sergey et al. (2010) Fluorescent proteins and their applications in imaging living cells and tissues. Physiol Rev 90:1103-63