Medicine@Yale U

Medicine@Ya le Advancing Biomedical Science, Education and Health Care Volume 1, Issue 2 August/September 2005 New look at how resistant bugs dodge drugs Yale biologists have opened a new Many widely used antibiotics mined the atomic-level structure of front in the war on antibiotic- work by latching onto and inhibiting five common antibiotics when the resistant bacteria by creating the first ribosomes, the protein factories drugs were bound to the ribosomes high-resolution pictures that show present in all cells. Using X-ray crys- of sensitive or resistant bacteria. how some resistant bacterial strains, tallography, Thomas A. Steitz, .., Although the antibiotics used in which threaten to undo years of Sterling Professor of Molecular the study have quite different chemi- progress against infectious disease, Biophysics and Biochemistry and a cal structures, Steitz and Moore thwart commonly used antibiotics. Howard Hughes Medical Institute found that they all bind to the same The new research, published in investigator, and Peter B. Moore, site on the ribosome’s large subunit In the ribosome of a resistant bacterium the April issue of Cell, provides .., Sterling Professor of and that resistance to all of them is (lower left), a “bulge” (red area at center) scientists with a fresh battle plan for Chemistry and professor of molecular generated by the same change in just keeps the antibiotic erythromycin (upper right) from binding tightly. creating new antimicrobial drugs. biophysics and biochemistry, deter- Ribosome, page 8 YALE PROJECTS FOR GLOBAL HEALTH RECEIVE MAJOR FUNDING Using laser light, team guides flies by remote control Researchers at the School of Medicine Richard Flavell will have created a high-tech puppet show, spearhead a new only their marionettes are alive and approach to vaccine development with a have no strings attached. With the $17 million grant from help of some genetic tweaking, the the Grand Challenges in team got fruit flies to walk, jump and Global Health initiative, fly on command—simply by flashing which is supported by a light at them. the Bill and Melinda Gates Foundation, the Over centuries, to better under- Wellcome Trust and the stand the brain’s normal functions Canadian Institutes of and the roots of disease, scientists Health Research and have devised many methods of managed by the manipulating animal behavior, but Foundation of the National Institutes they have had to rely on invasive tech- of Health. Flies, page 7 Mouse breakthrough will speed vaccines Fund will honor mentor, aid students All progress in biomedicine is made been subjected to over evolutionary on the horns of a dilemma. The Foiling malaria mosquitoes, p. 6 time, not the same set of pathogens This spring, when Applera Corp. of testing of drugs or other therapies that infect humans. And, as its Foster City, Calif., asked members of in humans before they are shown gap in knowledge, and only a small name implies, the immune system its board of directors to suggest likely to be safe and therapeutically fraction of the drugs that enter isn’t a unitary organ like the liver, worthy recipients for gifts from the promising in preclinical studies is clinical testing are eventually but a multifaceted mechanism dis- corporation, Carolyn W. Slayman, prohibited by ethical considera- approved for use in medicine. tributed throughout the body, .., the medical school’s deputy tions. But the tools available for This state of affairs has pre- which is difficult to emulate faith- dean for academic and scientific preclinical work—laboratory sented particular challenges in fully in a petri dish. affairs, suggested a grant that would animals or isolated cells in a dish— immunology research, says Richard “You don’t really want to be do double duty to promote her ideals are no substitute for testing in the A. Flavell, .., chair and Sterling studying mouse cells; you want to in biomedical education. living human body. Professor of Immunobiology. Mice, study human cells, and ultimately Slayman, a director of Applera— Bringing a potential cure from the most commonly used research you study humans, in clinical the parent company of Applied laboratory science to human clini- animal, have immune systems that trials,” says Flavell, who is also a Biosystems, a manufacturer of scien- cal trials often requires an unset- are tailored to deal with the bacte- Howard Hughes Medical Institute tific equipment, and Celera, which tling leap across an unavoidable ria and viruses that the species has Flavell, page 6 played a major role in sequencing the Fund, page 6 Non-Profit Org. Inside this issue Medicine@Yale U. S. Postage Lifelines Strength in numbers P.O.Box PAID Arthur Horwich, seeking what’s Adding up proteins brings power New Haven, CT New Haven, CT never been seen, p. 2 to ovarian cancer test, p. 5 www.medicineatyale.org Permit No. In praise of talented teachers A demand for supplies Faculty are feted at Medical equipment reaches Commencement, p. 2 the needy,p.5 Tracking down autism Also A hunt for childhood disorder’s Advances, pp. 3, 5; Out & About,p.4; first traces, p. 3 Grants, p. 7; Awards, p. 8 Want to find out more about medicine at Yale? E-mail us at [email protected] or phone (203) 785-5824. Notable teachers Form leads receive high honors to function at Commencement At the medical school’s Commence- Solving the puzzles of ment ceremony on Harkness Lawn in protein folding may shed May, the Class of enjoyed their new light on Alzheimer’s day in the sun, basking in the admira- tion of family and It’s true that biologist Arthur L. friends. But faculty, Horwich, m.d., received last year’s too, were honored for Gairdner International Award for their many contribu- having “revolutionized our under- tions to education. standing about basic cellular func- For the first time, tions,” but to hear him talk, he’s not the Bohmfalk Prize Peter Aronson much different for teaching basic sci- from the twenty- Lifelines ences was awarded to something post- a husband-and- doctoral re- Arthur L. wife team, Marie- searchers who Horwich Arthur Horwich (third from right) in his element—amongst the graduate students, postdoc- Louise Landry, .., staff his lab. toral fellows and research scientists with whom he shares the lab bench. “I just have never matured beyond professor of labora- postdoc,” says Horwich, the Eugene Christian B. Anfinsen, ph.d., who P. Lifton, m.d., ph.d., an hhmi tory medicine, and Higgins Professor of Genetics, profes- showed in the early 1960s that the investigator who is chair and Peter S. Aronson, Marie-Louise Landry sor of pediatrics and a Howard Hughes sequence of amino acids in a nascent Sterling Professor of Genetics at .., the ...Long Medical Institute (hhmi) investigator. protein contains all the information it the medical school. Professor of Medicine and professor “I still work at the bench every day. I needs to fold from a chain into the Colleagues are amazed that, at of cellular and molecular physiology. still like to do my own experiments. I three-dimensional sheets and helices 54, Horwich still enjoys the rigors of The Bohmfalk Prize for teaching like to be able to live with and suffer of a functioning protein. running experiments. “He seems to clinical science went to Michael K. through the problems of understand- But in 1987, Horwich and col- have retained the enthusiasm for O’Brien, .., .., assistant clini- ing how things work side by side with leagues discovered that sometimes science that people who are more my own people, and I always have one proteins need help from other special- senior seem to lose—the day-to-day cal professor of surgery. or two things for myself that I consider ized proteins, aptly known as “chaper- excitement,” says Tony Hunter, ph.d., a Sharon K. Inouye, .., ..., my own laboratory struggle.” onins,” which serve as intracellular cell biologist at the Salk Institute and a professor of medicine, received the In his first-floor lab at the Boyer protein-folding machines. Horwich fellow Gairdner winner who was one Leonard Tow Humanism in Medicine Center for Molecular Medicine, was impressed to discover that these of Horwich’s early mentors. Award, while Catherine Chiles, .., Horwich has helped to solve, bit by bit, molecular chaperones will try up to 20 In his spare time, Horwich enjoys associate clinical professor of psychia- one aspect of what has long been times to properly fold an intractable fly-fishing, tennis and backpacking. try, won the Leah M. Lowenstein known as “the protein-folding protein. In terms of the energy the cell But after a few days on the river or in Prize, for excellence in the promotion problem,” the question of how newly must expend, Horwich notes,“it’s a the mountains, he’s eager to get back of egalitarian medical education. The made proteins transform from long very expensive process,” but misfold- to the Boyer Center. Each day in the first annual Alvin R. Feinstein Award chains of amino acids into three- ing is costly, too: misfolded proteins lab holds out the chance, however for outstanding clinical skills was dimensional structures. This folding are linked to hundreds of devastating small, he says,“to see something that’s . step is essential, because the shapes of disorders, including Alzheimer’s, not been seen before. There’s no sub- awarded to Ronald R. Salem, ., folded proteins determine their func- Parkinson’s and mad cow disease. stitute for it.” associate professor of surgery. tions; for proteins, loosely speaking, “This work is as basic to biology as Robert D. Auerbach, .., lec- anatomy is destiny. understanding the nature of genes turer in obstetrics, gynecology and Lifelines profiles the people who carry out the sci- Horwich’s work has built upon and how genes are expressed and entific, educational and clinical missions of the Yale reproductive sciences, was awarded that of Nobel laureate and biochemist translated into proteins,” says Richard School of Medicine.

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