• • Purdue College of Science | Spring 2017 MICHAEL ROSSMANN: HIS PATH TO PURDUE & DECADES OF DISCOVERY @PurdueScience INSIDE: ARTIFICIAL INTELLIGENCE :: ALUMNUS’S NEXT NASA MISSION Dr.JD For more than 50 years, Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences, walked to his labs in Lilly Hall and Hockmeyer Hall of Structural Biology from his West Lafayette home. It was a leisurely 30 -minute stroll, at just over a mile to the southern tip of the Purdue campus. However, if one adds up all of his trips, he has traveled a distance equal to a round trip to Rio de Janeiro, Brazil, and back again to Rio. During those walks down Grant Street — past the blocks of homes built in the early 20th century as Purdue University grew and through an expanding campus — Rossmann’s mind stormed with ideas. Ideas mulled on these walks have led to monumental discoveries in the field of structural biology. Rossmann’s discoveries have helped doctors under - stand, treat and even cure infections from alpha viruses, coxsackievirus B3, flaviviruses like dengue and Zika, and even the rhinovirus that causes the common cold. His latest work has been a collaborative effort with Richard Kuhn, professor of biological sciences and director of the Purdue Institute for Inflammation, Immunology and Infectious Disease, to study Zika virus. The virus has received widespread attention because of an increase in microcephaly — a birth defect that causes brain damage and an abnormally small head in babies born to some mothers infected during pregnancy — and reported transmission of the mosquito -borne virus in 33 countries. On March 31, 2016, Rossmann and Kuhn’s team was the first to determine the structure of Zika virus and, in January, the team also revealed the structure of Zika’s immature form. Both are critical steps in the development of effective antiviral treatments and vaccines. “The virus goes through a certain life cycle during its infection process,” Rossmann says. “Therefore, pro - cedures that interrupt this process are likely to block “I HAVE TOO MUCH WORK, TOO MANY PROJECTS viral replication.” Rossmann, a spry octogenarian, has published nearly 600 papers and received numerous awards and honors, THAT I WANT TO DO.” but his life has been more than these accomplishments. It has been a journey through 20th century science history. — ROSSMANN ON WHAT DRIVES HIM TO CONTINUE HIS RESEARCH He has learned from legends, met some of history’s greats and boosted Purdue Biological Sciences. EUROPEAN SON Rossmann’s family emigrated from Frankfurt, Germany, to England in 1939, as World War II ignited. Rossmann clearly remembers the Blitz, the Nazi bombing campaign of London from 1940 to ’41. “There were bombs every night,” he recalls. The family resided near London, but as the war raged, By Tim Brouk Rossmann spent many of his years at an English boarding Photo by / Charles Jischke Spring 2017 | 13 TIMELINE school, where his talents for mathematics and physics were first realized. MICHAEL At home he built radios and played with chemistry sets. In high school, Rossmann had the advantage of meeting some of the 20th century’s top scientists. Pioneering crystallographer Kathleen Lonsdale met with a teenage Rossmann after a talk. Lonsdale, the first woman inducted into the British Association for the Advancement of Science, inspired him to 19 19 pursue structural science throughout his academic career. Soon after the Allies’ victory, Rossmann enrolled in Regent Street Polytechnic and obtained bachelor’s and master’s degrees in math and physics ROSSMANN 56 59 from the University of London. OBTAINS PHD from University of With Max Perutz, is on the Then, while seeking a doctorate at the University of Glasgow, he heeded Glasgow; PUBLISHES THESIS “A Study second team ever to determine Lonsdale’s influence to jump into the quickly growing field of chemical crystal­ of Some Organic Crystal Structures ” the structure of a PROTEIN AT lography. The roots of defining the structures of viruses started here. NEAR-ATOMIC RESOLUTION Crystallography was a hot field in the 1950s, as atomic theory was becoming atomic structure. “We students were given crystals of small organic compounds and were expected to determine their structures,” Rossmann says. “The X-ray pattern is a bunch of spots, and from those spots, we deduced what the structures were like.” Rossmann’s thesis is titled simply “A Study of Some Organic Crystal Structures.” It was the beginning of a tremendous career that would yield 19 19 19 19 numerous accomplishments. After finishing the doctorate, Rossmann had his first taste of America 99 85 84 73 during a two-year postdoctoral stint under William Lipscomb, who would Becomes a fellow of AMERICAN Maps the structure Inducted into Discovers what would become later win a Nobel Prize for his work on boron chemistry. ASSOCIATION FOR THE of the COMMON NATIONAL ACADEMY known as ROSSMANN FOLD, Then it was back to the United Kingdom for a research associate position ADVANCEMENT OF SCIENCE COLD VIRUS OF SCIENCES a nucleotide -binding motif at the University of Cambridge found in enzymes under Max Perutz, who was to “I HAD COFFEE WITH obtain a Nobel Prize in 1962 for his work on the struc­ FRANCIS [CRICK] tures of hemoglobin. AND OTHERS EVERY Rossmann wrote most MORNING. HE WAS A of the computer pro­ grams on an early VERY STIMULATING electronic computer 20 20 20 FIGURE. LIFE IS A SET and worked closely with OF CIRCUMSTANCES.” Perutz to interpret many of the results. 02 03 10 “I believe I got there Maps the structure of a DENGUE Rossmann and Kuhn’ s team Rossmann CLUSTER because I was interested in solving VIRUS — the first of multiple col- is first to determine the SUPERCOMPUTER the mathematics of protein structures,” he says. “I saw it as a mathematical laborations with Purdue Biological STRUCTURE OF WEST NILE ESTABLISHED at Purdue problem.” Sciences colleague Richard Kuhn VIRUS Also during this time, Rossmann had another fortuitous meeting with a name that has been in textbooks for decades — Francis Crick. The Crick who with James Watson discovered the double-helix structure of DNA in 1953. “I had coffee with Francis and others every morning. He was a very stimulating figure,” Rossmann remembers. “Life is a set of circumstances.” After much success with Perutz and a new direction into biology, in 1964 20 20 it was time to leave the nest for his first stop as a professor: Purdue University. 17 16 Rossmann works on a brass model of the Rossmann and Kuhn’ s team determines Rossmann and Kuhn’ s team is first molecular structure of a virus. Photo circa the STRUCTURE OF IMMATURE STATE to determine the STRUCTURE OF 1973 courtesy of the College of Science. OF ZIKA VIRUS and the mechanism of ZIKA VIRUS ANTIBODY neutralization of Zika virus 14 | insights ‘SOME’ BECOMES MANY technology to the department, includ- push the boundaries of discovery and ing the Titan Krios [cryo-electron who continuously gets excited about Built in 2009, Hockmeyer Hall is a microscope] and K2 Summit direct new data that is generated in the lab. sleek space for Rossmann and the detector [camera], which have trans- But there is much more to his per- Purdue Structural Biology program. formed the field of structural biology sonality than simply being driven to Rossmann had spent thousands of by greatly increasing the speed and push the limits of structure resolu­ sunless days in the Lilly Hall base- resolution by which we view viruses tion. He is a passionate mentor who ment. His current office contains a and large macromolecular takes great pride in the successes of Michael Rossmann uses an tall, wide window with a view of an complexes.” his students, postdocs and research electron microscope in the Purdue Cryo-EM Facility. For open area of campus. Plans for devel- The multimillion-dollar FEI scientists. He still gets in early every most of his past 50 years of opment for the area circulate, but Titan Krios cryo-electron microscope morning with the same passion that research, X-ray inside his office, it’s a cozy, warm allows “2-D electron crystallography, he has shown for the 30-plus years I crystallography was the atmosphere. single particle analysis, cryo-electron have known him.” standard method to determine virus structure. Rossmann had eight tall book- microscopy, and dual-axis cellular Hockmeyer Hall displays sev- Now cryo-electron cases moved in. The shelves are filled tomography of frozen hydrated cell eral of Rossmann’s brass-and-steel microscopy can be used to with tomes of his field along with its organelles and cells.” The K2 Summit viral structure models in glass cases view some viruses in a more mathematical, chemical and physical camera brings ultra-high resolution about as big as your grandparents’ native state. building blocks. Just to the right of for cryo-electron microscopy. old television. Decades ago, a room his desk are three shelves with A binding mechanism is named would be dedicated to the structure simple black bindings. On each, after Rossmann, although he prefers so his colleagues could gather around years 1956 to 2016 are scrawled. to call it by its original name, the to study it, Rossmann says. Brass These are the theses of his many PhD nucleotide binding fold. Regardless rods, metal fastenings and colorful students. Structural biology evolves of the name used, the fold can be seen yarn showed the virus at the molecu­ with each title. The latest is throughout Rossmann’s structure lar level. It was like stepping into a “Structural Studies on Cell Entry of visualizations — whether they were bloodstream and seeing a virus Respiratory Enteroviruses” by Yue rendered through crystals, digitally, coming at you, he says.