June 20, 1995, NIH Record, Vol. XLVII, No. 13
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June 20, 1995 Vol. XLVII No. 13 "Still U.S. Depanment of Health The Second and Human Services Best Thing About Payday" National Institutes of Health IH Recori Widespread Concern Here Protein Folding Mystery Bomb Threat to Employees Explored in Seminar Unfolds, Say Grantees By Rich McManus By Alisa Zapp crowd ofNIH'ers goc a gri m tutorial in handling bomb threats and s.uspicious letters or packages on June 6 as a bomb expen from che Maryland fire marshal's office gave ciencists are now one seep closer co A cwo talks on campus, sponsored by che Division of Security Operations (DSO). Sso lving a problem char they've struggled Employees here find themselves the unformnate targets of cwo modes of social unrest at the with for 40 years-determining how proteins moment, observed Jim Sweat, DSO director: antigovernment militias and the so-called fold into the three-dimensional shapes crucial Unabomber, an individual whose letter-bombing campaign has extended into the ranks of for their function. scientists. Proteins control nearly every syscem in our Deputy Fire Marshal Warren Gott, assistant commander of the 15-person bomb squad and a bodies. Antibodies, enzymes, and many 23-year veteran of the fire marshal's office, co ld his audiences-one in Masur Auditorium, the hormones are proteins. A procein's three ocher in Naccher's _conference center-how co handle a bomb rhreac, how to cooperate during a dimensional structure decermines which search and evacuanon, and how co identify potential explosives. molecules it binds, which reactions ic "April 19 is a dace char no one will ever forget," he began, referring to the Oklahoma City catalyzes, and, to some excenc, where it is bombing of a federal office building. "There has been a great, great increase in the number of located in che cell. calls for service to our office, and throughout the country, since then. People are more aware, le is much easier co determine the order, or more suspicious of items now. All the kooks in the world are coming out of che woodwork sequence, of amino acids in a protein than it with their hoax devices and threats. Life has not been enjoyable lately." is co determine the protein's three-dimen Should a bomb threat come to an employee by phone, Gott said, it's important co ask sevecal sional structure. Although the sequence key questions: When is the bomb going to explode? Where is it right now? What does it look contains all the information necessary for like? Whac kind of bomb is it? correct folding, scientists still cannoc predict a "You should ask these questions in a smooch, continuing, rolling manner," he counseled. protein's final shape from its sequence. "The less information a caller provides, the less likely it's a credible threat." "If we could decipher the strucrures of Mose, but not all, bombers don't intend personal injury, he continued, and will call in a proteins from rheir sequences, we could better warning co avoid casualties. "They wane co destroy property co make a point, or puc fear into understand all sores of biological phenomena, you." The Unabomber, on the ocher hand, has never warned an eventual victim, he said. from carcinogenesis to AIDS," said Dr. James Ic's imporcanc for the recipient of a bomb threat co note not only che exact wording of the Cassatt, director of che Division of Cell threat but also such qualiries as rone of voice. background sounds, emotional state of the caller, Biology and Biophysics, N IGMS. "Then we and the kind of language used- irrational, well-spoken, raped, including some message? might be able co do more about these (See BOMB THREA T, Page 4) (See PROTEIN FOLDING, Page 2) Diane Shartsis Wax Named Teachers Learn About AIDS, ELISAs, and More Chief of Legislative Policy By Ruth Levy Guyer By Carla Garnett ne day of science will nor turn a kid into a scientist. T his was one iane Sharcsis Wax recently was 0 small demonstration for teachers, D appointed NIH associate director for one lesson plan. Bue if the teachers go back legislative policy and analysis, a position she to the classroom, do the experiment we did had held in an acting capacity since July today, and 'wow' the kids, then a workshop 1994. like chis will have served an imporcanc In her new pose, Wax provides leadership in funccion." all aspects of legislative activities for NIH, These were some of che comments of Dr. acts as a liaison Randall Ribaudo, a research scientist in the between agency Laboratory oflmmune Cell Biology, officials and Biological Response Modifiers Program, members of NCI, who ran one of chree recenc workshops Congress and at NIH in a series for Montgomery County develops strategies middle and high school teachers. The and policies to deal program is cosponsored by the Howard wirh Capirol Hill's Hughes Medical Instirure, Montgomery everchanging County Public Schools, and NIH. envHonment. Ribaudo scarred his session with a lecture "In chis office," about HIV, the AIDS virus, and the deadly she explained, "we disease ir causes. He explained how che work to ensure viruses attach to specific molecules on the chat proposed surfaces of cells in the immune system, then Diane Shartsis Wax legislative changes enter the cells and eventually destroy chem, will not have an leaving the immune system weakened and untoward impact on NIH activities. We vulnerable co attack by other infectious work co see chat NIH has the legislative agents. Rockville High School Teacher Edgar Walker authority it needs ro carry out its mission." Ribaudo went on co explain che theory and practices lab activities that he can take back to (See DIANE WAX, Page 5) (See TEACHERS, Page 6) his students. page 2 The Record June 20, 1995 PROTEIN FOLDING crystal structure. (Continued from Page 1) "Right now LINUS gives the same benefit disorders." as a poor crystal structure," Rose said. Now, NIGMS grantee Dr. George Rose "What is that useful fo r? A lot of chin gs." and postdoctoral fellow Rajgopal Srinivasan For example, he said, it could be used in ar Johns Hopkins Universit,., have developed conjunction with rhe Human Genome a method rhat promises co come closer than Projecr to classify proteins that might be ever before co cracking che protein-folding involved in generic disorders. Or it could be code. Rose and Srinivasan describe rhe used co speed the progress of targeted drug method, a computer program called LINUS, design. in a paper in Proteins: Structure, Function, "The most surprising thing about this work and Genetics due out in mid-June. is how these exceedingly simple ideas, crudely "There are a loc of programs to predicr expressed, can do so well in giving you the secondary structure-small-scale, localized gross conformation of the protein," Rose rwisrs in rhe protein-from sequence said. Of che seven structures he examined in information," said Cassatt. "Bur somehow his paper, LINUS predicted the gross overall Rose gees the overall structure. T har makes shape for all bur one. The predicted length his program unique." The LINUS computer program, which is "The most surp rising thing about Dr. Clair Francomano, chief, Medical Genetics named after chelate Nobel laureate Dr. Linus Branch, NCHGR, and associate professor, Pauling, is based on very simple assumptions. this work is how these exceedingly medicine and pediatrics, Center for Medical No two atoms are allowed to be in the same simple ideas, crudely expressed, can Genetics, johns Hopkins University Schoof of space ar the same time; amino acids are Medicine, has been selected as an Executive encouraged co be in the conformations most do so well in giving you the gross Leadership in Academic Medicine (ELAM) commonly seen in proteins; and hydropho conformation ofthe protein. " fellow. ELAM, a program sponsored by the bic, or "water-fearing," amino acids are Institute for Women's Health at Medical encouraged co cluster in the protected center and location of the more localized struc College ofPennsylvania and Hahnemann of the protein. tures-the helices and sheets-were almost University in Philadelphia, is the only indepth In its calculations, LINUS doesn't even use identical to known structures determined by national program that focuses on preparing the true structure for amino acids in the x-ray crystallography. women faculty in academic medicine for senior protein. Instead, it makes a gross approxima With further refinements, Rose expects the leadership positions. Francomano is one of25 tion. Every amino acid has rwo parts: a accuracy of che program ro increase dramati women chosen from a pool ofapplicant; from backbone char is common co all amino acids, cally. For example, in the research reported academic medical centers across the country. and a side chain unique to chat type of amino in his paper, Rose rold LINUS ro take bites ELAM fellows complete 3 weeks ofstudy and acid. LINUS replaces each side chain no larger than 50 amino acids. Now he is interaction, and work on independent projects which can range from 1 to 18 atoms-with a modifying rhe program to produce accurate throughout the academic year. single sphere chat varies in size depending on structure predicrions using much larger the type of amino acid. chunks. He also plans to enable LINUS to To predict a protein's structure, LINUS predict special prorein features such as divides rhe protein sequence into overlap disulfide bonds, prosthetic groups, and The NIH Record ping, bite-sized chunks. Starting with multiple subunits. Evencually, he hopes that Published biweekly ar B«hesda, Md.. by rhe Edirorial chunks only six amino acids long, LINUS LINUS will be useful co researchers all over Operations Branch, Division of Public Information, for randomly twists rhe amino acids into any of the world.