Events

April 1, 2019 at 4:00 pm

Nobel Winner Ramakrishnan: Quest for Structure of Biological Machine that Reads Our Genes, May 2

Nobel Prize laureate and Ohio University alumnus Dr. Venki Ramakrishnan will give a public lecture on “The Quest for the Structure of the Biological Machine that Reads Our Gene” on Thursday, May 2, at 7:30 p.m. in Walter Hall Rotunda.

“Everyone has heard of DNA. But by itself, DNA is just an inert blueprint for life. It is the ribosome—an ancient and enormous molecular machine made up of half a million atoms—that makes DNA come to life by turning our genetic code into proteins and therefore into us,” says Ramakrishnan, who works at the MRC Laboratory of Molecular Biology in Cambridge, England, one of the world’s leading research institutes.

Ramakrishnan won the 2009 Nobel Prize in Chemistry for his work on the structure and function of the ribosome, jointly with Thomas A. Steitz and Ada E. Yonath. He also received the Louis-Jeantet Prize for Medicine.

He was knighted in Great Britain in 2012 and in 2015 was elected President of the Royal Society for a five-year term. He is a member of the U.S. National Academy of Sciences, Leopoldina and EMBO, and a foreign member of the Indian National Science Academy.

Ramakrishnan earned a Ph.D. in Physics from the College of Arts & Sciences at Ohio University.

In addition to the public lecture, Ramakrishnan’s book will be for sale, and he will be available to sign them. Light refreshments will be served.

About the Race to Discover the Gene Machine

He recently authored the book Gene Machine: The Race to Decipher the Secrets of the Ribosome.

Colorful book cover for Gene Machine: The Race to Decipher the Secrets of the Ribosome“My book Gene Machine is a frank insider account of the race for the structure of the ribosome, a fundamental discovery in molecular biology, but one that could also lead to the development of better antibiotics against bacterial infections.

“But the book is also about the human messiness of science: the twists and turns of my career, initially being an outsider who gave up on physics to become a biologist, and then being the dark horse in a fierce competition with well-established groups,” he says.

“Gene Machine is also a frank and gossipy account of how science is done, with its mixture of insights and persistence as well as blunders and dead ends. It is also honest about how scientists behave, especially when the stakes are high, with their personalities, egos, insecurities and jealousies but also their kindness and generosity,” Ramakrishnan adds.

The book’s website notes that the “fascinating insider account … charts Ramakrishnan’s unlikely journey from his first fumbling experiments in a biology lab to being at the centre of a fierce competition at the cutting edge of modern science.”

Currently in his lab, Ramakrishnan is “interested in translational initiation in both bacteria and eukaryotes, as well as how certain viral sequences disrupt the process in eukaryotes. The control or deregulation of translational initiation in eukaryotes has been implicated in phenomena as disparate as cancer, memory and viral infection, and involves about a dozen initiation factors that bind to the small subunit of the ribosome at various stages, allowing it to scan along mRNA and eventually associate with the large subunit. We are also interested in termination in eukaryotes, and in quality control in translation. Although we have mainly used x-ray crystallography in the past, we are now mainly using high-resolution electron microscopy,” according to his website.

Dr. Venki Ramakrishnan, portrait with ribosome art from bookcover.

Dr. Venki Ramakrishnan. Photo by Max Alexander at emax@maxalexander.com.

About Venki Ramakrishnan

In his Nobel Prize biography, Ramakrishnan chronicles his life, starting with his birth in India to parents who were both professors and his decision not to pursue a medical career.

“I had made an agreement with my father, who wanted me to study medicine, that if I was awarded (the National Science Talent Scholarship) I could choose to study basic science. That decided, there was the further question of where to do my undergraduate studies. I briefly considered going to Madras, which would have reconnected me with my Tamil roots, but a faculty member in the physics department in Baroda, S.K. Shah, told me about a brand new curriculum they were introducing for their undergraduate course. It began with the Berkeley Physics Course, and was supplemented by the Feynman Lectures on Physics before moving on to more specialized areas,” he writes.

When it came time for graduate school, “my chairman N.S. Pandya brought to my attention a letter from the physics department at Ohio University, which said they were looking for qualified students for their graduate program. I wrote them a letter of inquiry and soon afterwards was accepted with a fellowship. I was living alone when the acceptance arrived, and was absolutely thrilled to be going to graduate school in the U.S.A., a land I associated with many of the great scientists whose textbooks I had studied, including Feynman, Purcell and others.”

At Ohio University, Ramakrishnan chose to work in solid-state theory with Tomoyasu Tanaka. “For my proposal, I had considered doing some theoretical work on biological systems, but since neither he nor I knew any biology, this did not go anywhere,” he writes, noting that while he pursued theoretical inquiries in ferroelectric phase transitions in potassium dihydrogen phosphate, he was drawn to experimental discoveries in biology.

It was getting married and becoming a stepfather that propelled Ramakrishnan to complete his physics thesis after some time at OHIO “on extracurricular activities. I went hiking and hopped on freight trains with my good friend and classmate Sudhir Kaicker, learned about western classical music from another friend, Anthony Grimaldi, played on the chess team, read literature, and went to concerts,” he writes.

“It was during this time that I met Vera Rosenberry (’74 BFA), who was majoring in painting and was introduced to me by mutual friends because, unusually for the early 1970s in Ohio, we were both vegetarian. After an intermittent courtship that lasted only 11 months in total, we were married in 1975. She has been my companion and friend ever since, and has not only done most of the work of raising our children but uprooted herself many times to move with me all over the U.S.A. and to England. The emotional support and stable home environment she provided has been invaluable to me and my work. During that time, in addition to painting, she also became a children’s book writer and illustrator, and has published over 30 books.”

Before finishing his thesis, Ramakrishnan “had already decided I was going to switch to biology.” Rethinking his earlier decision about medical school, he took the MCAT and interviewed at Yale, but he told them his true interest lay in research. He ended up in graduate school again, this time at the University of California, San Diego.

He also found himself back in some undergraduate biology courses and lab rotations. But after two years he determined he didn’t need another Ph.D. and took a post-doctoral position at Yale’s Molecular Biophysics and Biochemistry Department, where he said he felt his research and career “finally beginning to take shape.” But his physics-to-biology transition proved to be a non-traditional career path when he applied for faculty positions and he didn’t get any interviews.

He ended up at Oak Ridge National Laboratory’s new neutron-scattering facility. But it was Brookhaven National Laboratory that would provide the opportunity to pursue independent research.

“I began working with Steve (White) by helping to grow large amounts of bacteria in a Yale fermentation facility, but when I saw the low yields that were obtained by purifying proteins from native ribosomes from Bacillus stearothermophilus, I felt that there had to be a better way. Indeed there was, and I could not have been in a better place to find it,” he writes. His work soon turned to crystallography, or the arrangement of atoms in crystal solids. He was off to Cambridge for a sabbatical. And his passion for solving the ribosomal protein structures took shape.

Ramakrishnan nearly didn’t take his next job–at the University of Utah–out of fears of failing to secure external research grants. But he got his lab there up and running, focusing on solving ribosomal protein structures.

“Even before coming to Utah, I had ideas of solving the structure of the ribosome, beginning with its small or 30S subunit. These ideas and their scientific consequences are outlined in my Nobel lecture,” he said.

“As soon as we started, my insecurities about funding again set in. I could just imagine writing a grant application to NIH saying that we had no good crystals of the 30S subunit but had some ideas about how to get them, and that although a group had been working on good crystals of the 50S subunit for almost a decade, we had some ideas for how to solve our structure if we got good crystals. Having served on study sections myself, I could just imagine the peals of laughter that would go around the table as my application was considered. On the other hand, I knew that the LMB, where I had done my sabbatical, had a longstanding tradition of supporting exactly this kind of difficult but fundamentally important project. Apart from funding issues, I felt I would have access to world leaders in crystallographic methodology who could help me if I ran into technical problems.”

Soon Ramakrishnan was headed back to the Laboratory of Molecular Biology in Cambridge, taking a huge pay cut to tackle “the ribosome problem.” He soon found out that “instead of having a quiet niche to myself, we were in a flat-out race.”

Read more in his book, Gene Machine: The Race to Decipher the Secrets of the Ribosome.

 

 

 

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