Inside this issueCover storiesYALE PROJECTS FOR GLOBAL HEALTH RECEIVE MAJOR FUNDINGMouse breakthrough will speed vaccinesFinding new perfumes to foil a femme fataleA new front in the war on antibiotic-resistant bacteriaNew look at how resistant bugs dodge drugsFrom the pages of Cell to The Tonight Show’s stageUsing laser light, team guides flies by remote controlApplera Corp. boosts educationFund will honor mentor, aid studentsPartnershipsA quest to detect earliest signs of autismYale visit brings hope to paralyzed veteransGrants and contractsPeopleLifelines: Arthur Horwich, seeking what’s never been seen.New president of alumni body sees a bright future aheadOut & aboutAwards & honorsScienceConnecticut’s $100 million stem cell program good news for YaleAdvances: Taking a toll on parasitic infections | New kidney discovery may help heart | A chink in malignant melanoma’s armor?HealthOvarian cancer test exposes quiet killerFrom humble start at Yale, REMEDY thrivesAdvances: Patient to surgeon: I hear a symphonyEducationStudent explorations in the world of researchNotable teachers receive high honors at Commencement
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Lifelines: Arthur L. HorwichForm leads to functionSolving the puzzles of protein folding may shed new light on Alzheimer’s Arthur Horwich (third from right) in his element—amongst the graduate students, postdoctoral fellows and research scientists with whom he shares the lab bench. It’s true that biologist Arthur L. Horwich, M.D., received last year’s Gairdner International Award for having “revolutionized our understanding about basic cellular functions,” but to hear him talk, he’s not much different from the twenty-something postdoctoral researchers who staff his lab. “I just have never matured beyond postdoc,” says Horwich, the Eugene Higgins Professor of Genetics, professor of pediatrics and a Howard Hughes Medical Institute (HHMI) investigator. “I still work at the bench every day. I still like to do my own experiments. I like to be able to live with and suffer through the problems of understanding how things work side by side with my own people, and I always have one or two things for myself that I consider my own laboratory struggle.” In his first-floor lab at the Boyer Center for Molecular Medicine, Horwich has helped to solve, bit by bit, one aspect of what has long been known as “the protein-folding problem,” the question of how newly made proteins transform from long chains of amino acids into three-dimensional structures. This folding step is essential, because the shapes of folded proteins determine their functions; for proteins, loosely speaking, anatomy is destiny. Horwich’s work has built upon that of Nobel laureate and biochemist Christian B. Anfinsen, Ph.D., who showed in the early 1960s that the sequence of amino acids in a nascent protein contains all the information it needs to fold from a chain into the three-dimensional sheets and helices of a functioning protein. But in 1987, Horwich and colleagues discovered that sometimes proteins need help from other specialized proteins, aptly known as “chaperonins,” which serve as intracellular protein-folding machines. Horwich was impressed to discover that these molecular chaperones will try up to 20 times to properly fold an intractable protein. In terms of the energy the cell must expend, Horwich notes, “it’s a very expensive process,” but misfolding is costly, too: misfolded proteins are linked to hundreds of devastating disorders, including Alzheimer’s, Parkinson’s and mad cow disease. “This work is as basic to biology as understanding the nature of genes and how genes are expressed and translated into proteins,” says Richard P. Lifton, M.D., Ph.D., an HHMI investigator who is chair and Sterling Professor of Genetics at the medical school. Colleagues are amazed that, at 54, Horwich still enjoys the rigors of running experiments. “He seems to have retained the enthusiasm for science that people who are more senior seem to lose—the day-to-day excitement,” says Tony Hunter, Ph.D., a cell biologist at the Salk Institute and a fellow Gairdner winner who was one of Horwich’s early mentors. In his spare time, Horwich enjoys fly-fishing, tennis and backpacking. But after a few days on the river or in the mountains, he’s eager to get back to the Boyer Center. Each day in the lab holds out the chance, however small, he says, “to see something that’s not been seen before. There’s no substitute for it.” Lifelines profiles the people who carry out the scientific, educational and clinical missions of the Yale School of Medicine. 
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Medicine@Yale Magazine
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August/September 2005 Volume 1 Issue 2
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