combine their knowledge of chemistry, The fellowships are open to full-time graduate students working toward a Ph.D. biology, physics, surface technology, and in analytical chemistry who will have com- electronics to create devices that can be used for drug screening. In the June 1 pleted their second year of graduate studissue of Analytical Chemistry (p. 1979)7 ies by the time their fellowship begins. they used their techniques to immobilize The applicant's graduate advisor must be green fluorescent protein from the jellya member of the Division, and only one fish Aequorea victoria on a quartz surface. nomination per advisor will be accepted. To control the molecular orientation, the Applicants from previous years should protein was modified by genetic engineerreapply. In addition to the application ing: The mutant protein carries a continuforms, nominees must submit three letous sequence of several histidines (a "Histers of recommendation and undergraduate and graduate transcripts. Applications tag"). The histidines bind specifically to nitrilotriacetic acid—which is covalently available from Robert A Libby, Divibound to the quartz surface and loaded sion of Science Truman State University 100 East Normal Kirksville MO 63501with divalent cations such as Ni2+ and 4221 (816-785-7499- fax 816-785-4045; immobilize the protein The kinetics and libby@truman edu) binding constant of the process and the fluorescence properties of the protein are Drobed by a laser beam that enters the RESEARCH UPDATE auartz slide and the layer of bonded molecules at an anrie suitable for internal reThe art of arranging flection The ODtical properties of the proreceptors on a tein investigated by total internal reflection
surface The drug industry is constantly seeking new therapeutic agents that can bind to a receptor and thus influence central biological signaling reactions. Combinatorial chemistry has multiplied the number of compounds that can be synthesized, increasing the need for rapid (and cheap) methods of screening for biological activity. Nevertheless, many of the functional tests of promising molecules are still done with animal experiments. A different approach is being explored at the Swiss Federal Institute of Technology in Lausanne. Horst Vogel and his coworkers—30 graduate students and postdocs—are incorporating biological receptor molecules into artificial membranes on solid sensor surfaces. The ultimate goal is to build sensors with fully active membrane receptor proteins that could be used for drug screening. "Once you know how to do it, such a device can be built easily, and it will be cheap and rugged," Vogel predicts. The young scientists in Vogel's group
Total internal reflection fluorescence monitors jellyfish protein.
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Vogel seeks cheap and rugged devices.
The group is now concentrating on several methods to create membranelike, self-assembled mono- or bilayers on various surfaces (gold, quartz, optical waveguides). Recently the Lausanne group incorporated the photoreceptor rhodopsin, a member of the class of G-proteincoupled receptors, into an artificial membrane immobilized on a gold surface. The rhodopsin molecules are transmembrane proteins that receive extracellular signals and transmit them across the cellular membrane into the cell. The interaction of the activated receptor with its G proteins and the subsequent signal amplification steps were investigated by surface plasmon New Text "We expect to observe similar biologically important cascade reactions with other G-protein-coupled receptor proteins embedded within artificial membranes on solid surfaces This would be the
ecules can be bound in an ordered and directed manner on a surface. Although this setup is not yet a drug screening device, Vogel's group is moving closer to this goal. The researchers were successful in immobilizing Histagged neuroreceptors by the same technique and subsequently were able to screen different agonist and antagonist ligands for receptor binding by fluorescence measurements. Fast drug screening will require an ultimate breakthrough for using- functional array of sensors, each carrying an artifiassavs in novel drug screening devices " cial membrane with a different receptor New Text protein. The various compounds syntheCollaborations with the pharmaceutisized by combinatorial chemistry would cal industry and the financial support of flow over individual sensors. Molecules new funding sources for applied research that interact with the protein would give rise to a change in conformation and even- (so-called priority programs) of the Swiss National Science Foundation help drive tually to an ion current, features that can these projects. Another factor is the proxbe detected by a multitude of analytical imity of the laboratory to the industry and methods such as the above-mentioned research centers in microtechnology in fluorescence spectroscopy (and related the western part of Switzerland: in Lautechniques), IR spectroscopy on thin laysanne at the Swiss Federal Institute of New Text surface plasmon resonance, or elecTechnology and in Neuchatel at both the trochemistry. Depending on the equilibUniversity and the Center for Electronics rium constant between protein and ligand and Microtechnology. as few as 1000 molecules of a potential Vogel says that his research group is new drug could be sufficient to give a dean example of how interdisciplinary retectable signal A bilayer with incorposearch can help answer a seemingly simrated proteins can be built auicklv and ple question: How can one identify a easilv then used for several hours Bepromising molecule from a multitude of cause'the sensor's properties can change compounds synthesized by a machine? over time the researchers recommend makino- afresh one each day Veronika R. Meyer Analytical Chemistry News & Features, September 1, 1997 5 2 7 A
