Proteins, as everyone knows, are essential to life. They perform myriad tasks within the body, from carrying oxygen in our blood, to forming antibodies against infection, even working in our eyes to sense light. Fewer people, however, have heard of ribosomes – these are the microscopic factories within each cell that build each protein from amino acids, using information contained in the genes in our DNA that encode the order of amino acids that make up any given protein. An interesting curiosity is that ribosomes, which make proteins, are themselves made up of many proteins along with large pieces of RNA, and it is thought that very early in life, ribosomes contained just the RNA component.
Sir Venki (he was knighted in 2012 but seldom uses the title, being more familiarly known as just ‘Venki’) along with his fellow winners Thomas Steitz, of Yale University, and Ada Yonath, of the Weizmann Institute, Jerusalem, have between them worked out the structure of the ribosome.
"I knew the ribosome was going to be the focus of Nobel prizes. It stands at the crossroads of biology, and explains how information in our DNA is transformed into the proteins that make up a living being,” says Venki, who defined the structure of a key part of the ribosome between 2000 and 2002 and then went on to solve the entire ribosome in many states. Although delighted that the award puts this important bodily component on the front pages of the world’s press, his first act as a recipient was typically egalitarian – he criticised the Nobel selection process that sets a limit of three recipients per category, saying this overlooks the important work of many contributors.
Biochemistry is, quite literally, in Venki’s blood. His father, CV Ramakrishnan, was also a biochemist. Indeed, when Venki was born, in 1952 in the ancient Tamil Nadu temple town of Chidambaram, his father was in America, working with enzymologist David Green. Work often took both parents away, and in his early years Venki was raised by his aunt and grandmother. At the age of three, he moved with his parents to the Gujarati town of Baroda (now Vadodara). Shortly afterwards, his father encouraged his mother, R. Rajalakshmi to go and get a Ph.D. from McGill University in Canada, and agreed to take care of Venki during her absence. In Baroda, because of language difficulties, Venki was enrolled in the local English-speaking Catholic school but also spent a year and a half in Adelaide, Australia which he found both carefree and educational.
Returning to India he was inspired by a dedicated science and maths teacher, TC Patel. He enrolled in a one-year pre-science course at the local Maharaja Savajirao University of Baroda, and at the age of 16 was offered the National Science Talent Scholarship to study for a degree in physics in Baroda.
After graduating in 1971, Venki was offered a fellowship to study at Ohio University in the US, where he met his wife, the artist and children’s author Vera Rosenberry. They married in 1975 and Venki found himself, at 23, with a wife, step-daughter and soon a son on the way. He gained his PhD in 1976 and then, after some searching for a post that almost led to him working with fellow laureate Thomas Steitz, ended up studying biology for two years at the University of California, San Diego. In his second year, Venki came across an article in Scientific American by Don Engelman and Peter Moore about using neutron scattering for locating the proteins in the ribosome and was “fascinated." He wrote to Engelman and in 1978 was drafted into Moore’s team at Yale.
After a brief stint at Oak Ridge National Laboratory in Tennessee, in 1983 Venki moved to Brookhaven National Laboratory, New York, under Benno Schoenborn. Neutron scattering was not useful to obtain detailed atomic structures of biological molecules, so Venki took a crystallography course at Cold Spring Harbor in 1988, and in 1991 took a year’s sabbatical to the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge to learn crystallography under the sponsorship of Aaron Klug (1982 Chemistry Nobel Laureate) who was world famous for his work on chromatin and large molecular assemblies.
Shortly after returning from Cambridge, Venki left Brookhaven to accept an offer to join the University of Utah as Professor of Biochemistry. His team continued to solve the structure of proteins but Venki was determined to obtain a detailed structure of the ribosome’s 30S subunit. Due to the way that universities are funded and the high risk and uncertainties of the project, he approached the LMB which was well known for supporting long term challenging work on important problems. Thus in 1999, he moved back to Cambridge, despite a 40% pay cut. The first breakthrough came when they could see a somewhat fuzzy picture of the 30S subunit that was nevertheless detailed enough for Brian Wimberly to place several proteins and trace the central domain of the 30S subunit.
There then followed a race against Ada Yonath’s team to create a high-resolution structure of the 30S subunit (Steitz’s team at Yale was concentrating on a 50S subunit). Luckily, the team was offered use of the high-intensity Advanced Photon Source in Argonne. The results, says Ramakrishnan, were “stunning”, allowing the team to build a model within weeks and perform studies with antibiotics.
Venki is a member of the Royal Society (he was recently elected to succeed Sir Paul Nurse as its President) and the US National Academy of Sciences. Among other awards, he received the 2007 Louis-Jeantet prize for medicine as well as India’s second highest civilian award, the Padma Vibhushan.