‘solving’ biology’s most important molecule
According to microbiologist “Venki” Ramakrishnan, “We all have imposter syndrome,” a phenomenon described as self-doubt of intellect, skills, or accomplishments among high-achieving individuals.
In a much-anticipated lecture at the College of Science’s Frontiers of Science September 27, Ramakrishnan detailed “My Adventures in the Ribosome.” With a warm reminder to the standing-room-only crowd at the Natural History Museum of Utah (NHMU) he explained that there were setbacks, re-directs and moments of doubt for the microbiologist who helped solve the structure of biology's most important molecule yet shrouded in mystery ever since the discovery of the double-helix structure of DNA fifty years earlier. “Everything in the cell is either made by the ribosome or made by enzymes that are themselves made by the ribosome,” he says. The event was co-sponsored by the U's Department of Biochemistry, U Health and NHMU.
Whatever syndrome Ramakrishnan once suffered from, the Nobel Prize laureate learned to value change, whether it was pivoting from his early studies in physics — a discipline that dates back to Galileo in the 16th century — to that of biology, now in the midst of a resurgence, supercharged with the advent of genetics. (To the PhD physicist “lambda” was a wavelength, not a virus, he shared with the audience, garnering laughs.)
In his new life science digs, he soon gravitated to capturing the essence of an enormous molecular machine made up of a million atoms — wherein large, complex protein molecules are produced, turning the genetic code into organisms.
If you want to see the world
Finding the structure of the ribosome wasn’t easy. For one thing, it entailed uprooting his family. In his presentation, Ramakrishnan repeatedly displayed a travel map with dotted lines to illustrate how, if you want to see the world, study the ribosome. He and eventually his family traveled from his home in India to Ohio to San Diego before beginning his postdoctoral work with Peter Moore at Yale University in Connecticut, and then a sabbatical in Cambridge, England, to Utah, where he was on the biochemistry faculty for more than four years. (A U lab staff photo projected at the event prompted Ramakrishnan to refer to himself, heavily-bearded in the 1990s photo, as being his “bin Laden days.”)
From Utah he returned to Cambridge, England and the MRC Laboratory of Molecular Biology where he is currently group leader.
The race for solving the ribosome turned into a four-way contest of labs and turned on securing the right level of detail to see how the ribosome actually works–from x-ray technology to eventually crystallography facilitated by the U’s own Chris Hall and others determined to solve a fundamental problem regardless of the challenges.
Fifteen years after the first crystals and there was still no apparent progress towards determining the actual structure of the ribosome. In Utah, Ramakrishnan and his lab focused on what had earlier been identified as the smaller subunit of the ribosome, but it wasn’t until his return to the UK that the goal of bagging atomic resolution crystals of both ribosome units was accomplished. This with the help of electron microscopy as well as circular particle accelerators known as synchrotrons used by his team and his Yale colleagues.
Finally, there was enough detail to hazard a “mission accomplished,” and in 2009 Ramakrishnan, now elected to The Royal Society, shared the Nobel prize in chemistry with Thomas A. Steitz and Ada Yonath for research on the structure and function of ribosomes. In 2012 he was knighted.
Not bad for someone who claims to be subject to sometimes crippling self-doubt, and he was eager to share some take-aways to the audience for not only scientific research success, but life success. In addition to his recurring refrain that we all suffer from imposter syndrome, Ramakrishnan referenced the late Max Perutz, the Austrian-born British molecular biologist who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of hemoglobin and myoglobin. Perutz charted the variables at play for success in the scientific realm beyond just talent: money, skill, patience and luck.
And Ramakrishnan's advice?
- Keep your options open, even if it means learning completely new techniques, moving, or even changing fields
- Never be afraid to ask for help or show your ignorance
- Talk to people but not all the time
Of course, “success” is never final for a scientist, perhaps especially for one traversing the mysterious inner galaxies of molecules. And this is where Ramakrishnan brought his journey back to a recognizable metaphor for the uninitiated. In a series of slides, he showed the structure of this mighty molecular machine, including where antibiotics bind to the molecule which has advanced our understanding of how the ribosome works and how antibiotics inhibit it.
It took ten to fifteen years of taking snapshots of the ribosome to get a full complement of intricate, uniquely shaped moving images at an atomic resolution that could then be fitted together like a jigsaw puzzle. Finally, biologists could see and render the long-enigmatic process that takes place from the blueprint of DNA to protein: where exactly mRNA entered, how other proteins attached, and where the amino acid chain exited from the ribosome.
Each of the slides at the Tuesday night event presented a progressively more detailed model of the ribosome, until it was three-dimensional. In his visual piece de la resistance, Ramakrishnan put up an animation of the completed jigsaw puzzle designed by Janet Iwasa and the U’s animation lab. The frenetic choreography of multi-colored components wowed the audience, especially when the good scientist put it up to speed and the illustrated ribosome seemed to go kinetically cosmic before everyone’s very eyes.
The animation is featured in a new exhibit dedicated to the ribosome on the fourth floor of the Natural History Museum of Utah.
It was a stirring finish for Venki Ramakrishnan who brought it all up to scale when he closed the evening by saying, “During the time you've been listening to me, the thousands of ribosomes in each of your cells have been churning out tens of thousands of proteins as we speak."
Read Michael Mozdy’s post about Dr. Ramakrishnan and the new Ribosome exhibit at the NHMU.
By David Pace
About Frontiers of Science
The College of Science Frontiers of Science lecture series was established in 1967 by University of Utah alumnus and Physics Professor Peter Gibbs. By 1970, the University had hosted 10 Nobel laureates for public Frontiers lectures. By 1993, when Gibbs retired, the Frontiers organizers had hosted another 20 laureates. Today, it is the longest continuously running lecture series at the U.
The next event in the series takes place March 19, 2024 and will feature Maureen Raymo, American paleoclimatologist and marine geologist.