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Dr.JD

Purdue College of Science | Spring 2017

MICHAEL ROSSMANN: HIS PATH TO PURDUE & DECADES OF DISCOVERY @PurdueScience

INSIDE: ARTIFICIAL INTELLIGENCE :: ALUMNUS’S NEXT NASA MISSION

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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 viral replication.”

Rossmann, a spry octogenarian, has published nearly 600 papers and received numerous awards and honors, but his life has been more than these accomplishments. It has been a journey through 20th century science history. 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,

Rossmann spent many of his years at an English boarding

“I HAVE TOO MUCH WORK, TOO MANY PROJECTS THAT I WANT TO DO.” — ROSSMANN ON WHAT DRIVES HIM TO CONTINUE HIS RESEARCH

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school, where his talents for mathematics and physics were first realized. 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 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 from the University of London.

Then, while seeking a doctorate at the University of Glasgow, he heeded Lonsdale’s influence to jump into the quickly growing field of chemical crystal­lography. The roots of defining the structures of viruses started here. 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 numerous accomplishments.

After finishing the doctorate, Rossmann had his first taste of America during a two-year postdoctoral stint under William Lipscomb, who would later win a Nobel Prize for his work on boron chemistry.

Then it was back to the United Kingdom for a research associate position at the University of Cambridge

under Max Perutz, who was to obtain a Nobel Prize in 1962

for his work on the struc­tures of hemoglobin. Rossmann wrote most of the computer pro­grams on an early electronic computer

and worked closely with Perutz to interpret many

of the results. “I believe I got there

“I HAD COFFEE WITH FRANCIS [CRICK] AND OTHERS EVERY MORNING. HE WAS A VERY STIMULATING FIGURE. LIFE IS A SET OF CIRCUMSTANCES.”

because I was interested in solving the mathematics of protein structures,” he says. “I saw it as a mathematical problem.”

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 it was time to leave the nest for his first stop as a professor: Purdue University.

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59 OBTAINS PHD from University of

Glasgow; PUBLISHES THESIS A Study of Some Organic Crystal Structures

MICHAEL

ROSSMANN With Max Perutz, is on the

second team ever to determine the structure of a PROTEIN AT NEAR-ATOMIC RESOLUTION

Inducted into NATIONAL ACADEMY

OF SCIENCES

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73 Discovers what would become known as ROSSMANN FOLD,

a nucleotide binding motif found in enzymes

TIMELINE

Maps the structure of the COMMON

COLD VIRUS

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03 Rossmann and Kuhn s team

is first to determine the STRUCTURE OF WEST NILE

VIRUS

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16 Rossmann and Kuhn s team is first to determine the STRUCTURE OF

ZIKA VIRUS

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10 Rossmann CLUSTER SUPERCOMPUTER

ESTABLISHED at Purdue

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02 Maps the structure of a DENGUE

VIRUS — the first of multiple col laborations with Purdue Biological Sciences colleague Richard Kuhn

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99 Becomes a fellow of AMERICAN

ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE

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17 Rossmann and Kuhn s team determines

the STRUCTURE OF IMMATURE STATE OF ZIKA VIRUS and the mechanism of ANTIBODY neutralization of Zika virus

Rossmann works on a brass model of the molecular structure of a virus. Photo circa 1973 courtesy of the College of Science.

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‘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 resolu­sunless 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 la rge macromolecu lar takes great pride in the successes of Michael Rossmann uses an

electron microscope in the tall, wide window with a view of an complexes.” his students, postdocs and research 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 r e s e a r c h , X - r a y cr y s t al logr aphy w as the s t a n d a r d m e t h o d t o

inside his office, it’s a cozy, warm allows “2-D electron crystallography, he has shown for the 30-plus years I atmosphere. single particle analysis, cryo-electron have known him.”

determine virus structure. Rossmann had eight tall book- microscopy, and dual-axis cellular Hockmeyer Hall displays sev- N o w c r y o - e l e c t r o n cases moved in. The shelves are filled tomography of frozen hydrated cell eral of Rossmann’s brass-and-steel microscopy can be used to

view some viruses in a more native state.

with tomes of his field along with its organelles and cells.” The K2 Summit viral structure models in glass cases mathematical, chemical and physical camera brings ultra-high resolution about as big as your grandparents’ 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 molecu­with 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. Liu, now a postdoctoral researcher. or by hand with brass and steel Today, Rossmann’s work is His office is kitty-corner to three-dimensional models. The digitally rendered. Rossmann and Rossmann’s. Rossmann fold touches on the motif Kuhn’s work on Zika was seen in

Liu can give insight into life as found in enzymes like dehydroge- hundreds of mainstream media a postdoctoral researcher or gradu- nases or kinases that connect mol- outlets just 24 hours after the spheri­ate student under Rossmann. First, ecules such as adenosine triphos- cal virus structure was released. you get published fast. There are a phate or nicotinamide adenine Like his colleagues in the lot of human viruses out there that dinucleotide. Department of Computer Science, need more precise imaging. He Konieczny says he was familiar Rossmann knew to embrace digital believes that a fast research accom- with the Rossmann fold when he technology early. Before computers plishment gets graduate students’ came to Purdue in 1986. While con- were available, he would perform three or four years, there has been a STILL WALKING Also, his dedication to his PhD careers rolling. centrating on the cancer and genetic written calculations, often ending the big change in the way we study students makes him want to keep

“He’s really supportive. He arms of biology, Konieczny and his day with aching hands and strained structure as a consequence of detec- Rossmann now lives at University working. He beams with pride when wants you to explore everything,” wife, Elizabeth Taparowsky — a eyes. He was happy — and relieved tors for electrons. Place, a retirement community in he speaks of these successful scien­says Liu, who received his under- fellow biological sciences professor — when computers started rolling “We can use an electron micro- West Lafayette, significantly farther tists. His current crop of students and graduate degree in chemistry at the and College of Science associate dean into research in the 1950s. scope, which is just like a light from Purdue than his old home. He postdoctoral researchers represents Beijing Institute of Technology. of research and graduate education He used computers in his microscope, but instead of light it accepts vehicular transportation to India, China, Indonesia, Germany,

Rossmann’s presence has — were excited to join a department research so much that in 2010, uses electrons. Electrons have a work these days, but he still carves Russia and Nepal. They are all work-become a recruitment tool for attract- that contained a researcher like Rossmann was given the honor of much shorter wavelength. So with out about 30 minutes per day to walk ing on solving different viruses — ing young faculty, graduate students Rossmann. having a new Purdue supercomputer electron microscopes, we can see around Discovery Park. Ideas and like a global all-star team. and postdocs. “Having someone of Michael’s cluster named after him. That year, atoms. Light microscopes, you can’t solutions to problems are still being “I feel very fortunate having an

“Michael’s research career has stature in the department definitely the Rossmann cluster was ranked because the light wavelength is too worked out during these strolls. international family of students all elevated the status of our department played into our decision to join the 126th most powerful computer in long. You get direct imaging of what What drives him to continue his over the world,” Rossmann says. in innumerable ways,” says Stephen Purdue,” he remembers. “We all enjoy the world by the TOP500 project, you want to look at, but to do that, we research at the age of 86 is the ever- And the admiration is mutual. Konieczny, interim head of the working around talented individuals, which ranks supercomputers and is still have enormous computing prob- evolving nature of viruses. Humans Liu is happy to still be in Hockmeyer, Department of Biological Sciences and Michael certainly is one such l inked to the International lems because we have to take hun- must stay a step ahead of these just several steps away from a struc­and eukaryotic molecular biology example. Supercomputing Conference. dreds of thousands of images of the organisms. tural biology icon. professor. “He has put the depart- “Michael is the ultimate role “We needed powerful computers virus in different orientations. Saving “I have too much work, too many “He’s always positive,” Liu says. ment on the map … . He also has model for anyone who is passionate and we still need powerful comput­ all of that data in systematic ways projects that I want to do,” he says. “He always loves challenges, and he been a leader in bringing amazing about science, who always wants to ers,” Rossmann says. “In the last takes tremendous resources.” never gives up.”

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