Remembering Michael Rossmann

05-16-2019

Read the full version of the 2017 Insights interview (PDF)

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, procedures 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 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 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.

'Some' Becomes Many

Build in 2009, Hockmeyer Hall is a sleek space for Rossmann and the Purdue Structural Biology program. Rossmann had spent thousands of sunless days in the Lilly Hall basement. His current office contains a tall, wide window with a view of an open area of campus. Plans for development for the area circulate, but inside his office, it's a cozy, warm atmosphere.

Rossmann had eight tall bookcases moved in. The shelves are filled with tomes of his field along with its mathematical, chemical and physical building blocks. Just to the right of his desk are three shelves with simple black bindings. On each, years 1956 to 2016 are scrawled. These are the theses of his many PhD students. Structural biology evolves with each title. The latest is "Structural Studies on Cell Entry of Respiratory Retroviruses" by Yue Liu, now a postdoctoral researcher. His office is kitty-corner to Rossmann's.

Liu can give insight into life as a postdoctoral researcher or graduate student under Rossmann. First, you get published fast. There are a lot of human viruses out there that need more precise imaging. He believes that a fast research accomplishment gets graduate students' careers rolling.

He's really supportive. He wants you to explore everything," says Liu, who received his undergraduate degree in chemistry at the Beijing Institute of Technology.

Rossmann's presence has become a recruitment tool for attracting young faculty, graduate students and postdocs.

Michael's research career has elevated the status of our department in innumerable ways," says Stephen Konieczny, interim head of the Department of Biological Sciences and eukaryotic molecular biology professor. "He has put the department on the map . . . He also has been a leader in bringing amazing technology to the department, including the Titan Krios [cryo-electron microscope] and K2 Summit direct detector [camera], which have transformed the field of structural biology by greatly increasing the speed and resolution by which we view viruses and large macromolecular complexes."

The multi-million-dollar FEI Titan Krios cryo-electron microscope allows “2-D electron crystallography, single particle analysis, cryo-electron microscopy, and dual-axis cellular tomography of frozen hydrated cell organelles and cells." The K2 Summit camera brings ultra-high resolution for cryo-electron microscopy.

A binding mechanism is named after Rossmann, although he prefers to call it by its original name, the nucleotide binding fold. Regardless of the name used, the fold can be seen throughout Rossmann's structure visualizations - whether they were rendered through crystals, digitally, or by hand with brass and steel three-dimensional models. The Rossmann fold touches on the motif found in enzymes like dehydrogenases or kinases that connect molecules such as adenosine triphosphate or nicotinamide adenine dinucleotide.

Konieczny says he was familiar with the Rossmann fold when he came to Purdue in 1986. While concentrating on the cancer and genetic arms of biology, Konieczny and his wife, Elizabeth Taparowsky — a fellow biological sciences professor and College of Science associate dean of research and graduate education — were excited to join a department that contained a researcher like Rossmann.

“Having someone of Michael’s stature in the department definitely played into our decision to join Purdue," he remembers. "We all enjoy working around talented individuals, and Michael certainly is one such example.

"Michael is the ultimate role model for anyone who is passionate about science, who always wants to push the boundaries of discovery and who continuously gets excited about new data that is generated in the lab. But there is much more to his personality than simply being driven to push the limits of structure resolution. He is a passionate mentor who takes great pride in the successes of his students, postdocs and research scientists. He still gets in early every morning with the same passion that he has shown for the 30-plus years I have known him."

Hockmeyer Hall displays several of Rossmann's brass-and-steel viral structure models in glass cases about as big as your grandparents' old television. Decades ago, a room would be dedicated to the structure so his colleagues could gather around to study it, Rossmann says. Brass rods, metal fastenings and colorful yarn showed the virus at the molecular level. It was like stepping into a bloodstream and seeing a virus coming at you, he says.

Today, Rossmann's work is digitally rendered. Rossmann and Kuhn's work on Zika was seen in hundreds of mainstream media outlets just 24 hours after the spherical virus structure was released.

Like his colleagues in the Department of Computer Science, Rossmann knew to embrace digital technology early. Before computers were available, he would perform written calculations, often ending the day with aching hands and strained eyes. He was happy — and relieved — when computers started rolling into research in the 1950s.

He used computers in his research so much that in 2010, Rossmann was given the honor of having a new Purdue supercomputer cluster named after him. That year, the Rossmann cluster was ranked the 126th most powerful computer in the world by the TOP500 project, which ranks supercomputers and is linked to the International Supercomputing Conference.

"We needed powerful computers and we still need powerful computers," Rossmann says. "In the last three or four years, there has been a big change in the way we study structure as a consequence of detectors for electrons.

"We can use an electron microscope, which is just like a light microscope, but instead of light it uses electrons. Electrons have a much shorter wavelength. So with electron microscopes, we can see atoms. Light microscopes, you can't because the light wavelength is too long. You get direct imaging of what you want to look at, but to do that, we still have enormous computing problems because we have to take hundreds of thousands of images of the virus in different orientations. Saving all of that data in systemic ways takes tremendous resources."

Still Walking

Rossmann now lives at University Place, a retirement community in West Lafayette, significantly farther from Purdue than his old home. He accepts vehicular transportation to work these days, but he still carves out about 30 minutes per day to walk around Discovery Park. Ideas and solutions to problems are still being worked out during these strolls.

What drives him to continue his research at the age of 86 is the ever-evolving nature of viruses. Humans must stay a step ahead of these organisms.

"I have too much work, too many projects that I want to do," he says.

Also, his dedication to his PhD students makes him want to keep working. He beams with pride when he speaks of these successful scientists. His current crop of students and postdoctoral researchers represents India, China, Indonesia, Germany, Russia and Nepal. They are all working on solving different viruses — like a global all-star team.

"I feel very fortunate having an international family of students all over the world," Rossmann says.

And the admiration is mutual. Liu is happen to still be in Hockmeyer, just several steps away from a structural biology icon.

"He's always positive," Liu says. "He always loves challenges, and he never gives up."

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