NEWS OF THE W EEK
CHEMICAL BIOLOGY: RNAbased detector monitors molecules in live cells
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AGGING NONFLUORESCENT molecules in live
biological cells with fluorescent proteins has allowed researchers to visualize the hustle and bustle taking place in these membrane-bound metropolises and was an innovation that garnered the 2008 Nobel Prize in Chemistry. Now, researchers led by Samie R. Jaffrey at Weill Cornell Medical College in New York City have developed a new sensor, based on RNA instead of protein, that can also use fluorescence to image small molecules and proteins in living cells (Science, DOI: 10.1126/science.1218298). The new RNA sensors can likely be modified to detect a broad range of metabolites, including some that cannot currently be visualized with protein-based fluorescent tags. This “alternative approach to image and study small-molecule metabolites is an important piece of work and will potentially have broad applications,” comments Taekjip Ha, who develops fluorescencebased imaging methods at the University of Illinois, Urbana-Champaign. The sensor could find application in a wide range of research, from screening metabolites in cells involved in diabetes, neurodegenerative disease, or cancer to helping drug developers evaluate how their medicines are metabolized, Jaffrey says. The new sensor relies on an RNA-fluorophore complex that Jaffrey and his colleagues reported last
summer in Science (DOI: 10.1126/science.1207339). When an engineered RNA called Spinach interacts with the fluorophore 3,5-difluoro-4-hydroxybenzylidene imidazolinone(DFHBI), the complex produces a bright green color. To make a sensor that can report the presence of specific biological molecules, Jaffrey’s team extended Spinach by adding a second RNA component that can bind different biological molecules or metabolites of interest, such as adenosine diphosphate, guanine, or S-adenosylmethionine. When the molecule of interest is not bound, the sensor is unfolded and therefore cannot form a fluorescing complex. When the analyte is bound, the sensor is
folded, binds DFHBI, and shines green. Geoffrey F. Strouse, a chemist at Florida State University, notes that this new sensor faces a stumbling blockinherenttomanyfluorescence-imagingmethods— that inserting the RNA into cells may alter the production of metabolites one wishes to measure, a biological version of the Heisenberg uncertainty principle that observing a system inherently changes it. Nevertheless, he says the new approach is“a truly transformative development in molecular beacon technology.”—SARAH EVERTS SCIENCE
NEW SENSOR FOR CELL METABOLITES
Escherichia coli cells emit little fluorescence when analytes are not bound to the RNA sensors they contain (left) but turn green when analytes bind (right).
RESEARCH SUPPORT New ventures aim to advance innovation in drug discovery Institutional support for drug research has advanced with the formation of a venture sponsored by Cleveland’s University Hospitals (UH) to support independent scientists and a collaboration between the Boston area’s two National Cancer Institute-designated cancer centers. UH has launched a $250 million initiative called the Harrington Project for Discovery & Development to support drug research by independent physicianscientists. The project will be funded by UH, independent investors, and a $50 million gift from the local family for
which it is named. It will include a not-forprofit clinical research group and a forprofit company that will commercialize drugs that it develops. The Harrington Project, according to UH, is a first-of-its-kind venture to support researchers who lack access to government and investor funding or partnerships with major drug companies. “The current system nationally has been flawed, and we believe this new initiative is the solution,” says Achilles A. Demetriou, UH’s chief operating officer. Meanwhile, in a first-time collaboration,
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the David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology and Dana-Farber/ Harvard Cancer Center have formed the Bridge Project to tackle two of the most lethal cancers: pancreatic cancer and glioblastoma, a form of brain cancer. The Bridge Project has awarded grants to four teams made up of biologists, bioengineers, and clinical researchers representing both cancer centers. The project aims to raise $50 million over the next three to five years to fund additional research teams.—RICK MULLIN
