Ramakrishnan: Nobel-winning work started in Utah

Published October 11, 2009 8:24 am

Science » Biochemist tips hat to U. colleagues who helped map ribosome structure.
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William Clemons recalls sitting in an empty lab with his mentor and friend, former University of Utah biochemist Venkatraman "Venki" Ramakrishnan, when they brewed up a plan to go boldly where no scientist had gone before -- deep into the structural heart of ribosomes, the protein-building equipment in the nuclei of all cells.

The idea was to crystallize bacteria ribosomes, then shower them with X-rays, said Clemons, a graduate student at the time in 1995 and now an assistant professor of biochemistry at Caltech. By analyzing how the rays scattered, they hoped to map the million of atoms -- give or take -- that make up a ribosome molecule.

Both were new to Utah, their pricey lab equipment had yet to be installed. Neither could have imagined that 14 years later this plan, whose objective seemed almost out of reach, would garner Ramakrishnan and two other ribosome mappers a Nobel prize.

His path from the small Tamil town of Chidambaram, India, to the top prize in science, passed through the U.'s Maxwell Wintrobe Research Building. This is where Ramakrishnan toiled in the late 1990s, making key breakthroughs, before moving to England to step up his research.

"I started the whole project in Utah because it was the important question in my field. I had so many years in my career and I didn't want to waste it on little things. I wanted to go for the real questions," Ramakrishnan said in a phone interview from his lab at the Medical Research Council (MRC) in Cambridge.

Unraveling the ribosome is one of science's Holy Grails. Were God a molecule, he or she would be a ribosome, a veritable galaxy of atoms whose job is to translate genetic code into the stuff of life--protein. Mapping the ribosome's structure is the kind of basic research whose potential applications take years to become apparent, but already others are using this knowledge to improve antibiotics.

At Utah he could study big picture

Ramakrishnan started his career in physics, but early on he found the research being done in the life sciences much more engaging. He began picking at ribosome structures while a researcher at the Brookhaven National Laboratory, but Utah came knocking, offering him a chance to examine the big picture.

"I was doing pieces of the ribosome, a little at a time. When I came to Utah, I wanted to work on the whole thing. The technology developed to a point where it became possible," he said.

"If you want to know how a car works you need a picture of the whole engine. You can't know from a picture of a cylinder out of context," Ramakrishnan continued. "A ribosome is a machine just like a car -- it uses energy and it moves -- except it's a molecule."

In 1991 he spent his sabbatical at the MRC, where he shared a lab bench with Wesley Sundquist, then a post-doctoral fellow who would soon be heading to the U.'s biochemistry department. He encouraged Ramakrishnan to consider joining him in Utah.

"At that time it was clear he was a special scientist," said Sundquist, now the department co-chair. "He solved the crystal structures of two proteins that year. That was an amazing accomplishment, but it was even more amazing because he had never done crystallography before."

Utah had an accomplished protein crystallographer on board, Christopher Hill, who had already put together an X-ray facility, as well as Brenda Bass and other top researchers in RNA, one of the key components in ribosomes.

Ramakrishnan visited and liked what he saw. A few years later he was on the faculty chasing his dream.

"I found it a dynamic place and I like the outdoors and hiking," Ramakrishnan said. But his stay proved short.

Visit to SLC planned by end of year

Scientists regard the MRC's Laboratory of Molecular Research in Cambridge as "the Mecca" for structural biology and its ability to guarantee long-term funding is what lured Ramakrishnan from Utah in 1999, despite a big salary cut.

"If I was very bold and been in Utah a long time with a lot of credibility, I could have stayed and done it," Ramakrishnan said. The National Institutes of Health, which pays for most health-science research on U.S. campuses, issues grants in funding cycles of three to five years. Ramakrishnan feared his project would exceed that funding window before he could demonstrate sufficient progress to secure an extension.

"I had brilliant colleagues and good friends [in Utah]. I went to an institution with a long reputation of doing exactly this thing, not huge funding, but stable funding," he said. Clemons and Utah colleague Brian Wimberly followed Ramakrishnan to England and co-authored key papers on ribosomal structures.

Ramakrishnan feels so indebted to the U. and his former colleagues here that he said he intends to visit Salt Lake City by the end of the year to pay homage to both his friends and the institution that supported him.

Likewise, the news out of Stockholm cheered Ramakrishnan's old colleagues, who fondly recall him as a strong hiker with an affinity for Wasatch trails and a warm friend who played a mean game of Trivial Pursuit. But...

"He ate, drank and slept ribosomes. His kids didn't like it when I came around for family events because we would end up talking science," Clemons said.

Unlocking the key to life

Venkatraman Ramakrishnan shares the Nobel Prize in Chemistry with Thomas A. Steitz, of Yale University, and Israeli scientist Ada Yonath for their atom-by-atom description of ribosomes. Regarded as the key to life, ribosomes use instructions from genes to make thousands of proteins that control what happens in the body. He started this work at the University of Utah in the late 1990s with colleagues William Clemons, Brian Wimberly, Joanna May, John McCutcheon and others. Since 1999, Ramakrishnan has worked at the Laboratory of Molecular Biology of the Medical Research Council in Cambridge, England, where he used X-ray crystallography to map the atomic structures of ribosomes.

Ramakrishnan is married to the illustrator Vera Rosenberry, known for her "Vera" children's books. They have two grown children. Daughter Tanya is a physician and son Raman is a professional musician and holds a degree in physics from Harvard.



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