The 2009 Nobel Prize in Chemistry was awarded to three scientists for mapping the ribosome at the atomic level. The pioneering work was performed by the Israeli crystallographer Ada Yonath, who dedicatedly and persistently continued to reveal the large and complex ribosome structure at a time when many believed it was impossible.
I met Ada Yonath for a chat in the beautiful Thavenius parlor at the Grand Hotel in Stockholm on 5 December 2009. She then had a couple of busy and eventful days ahead of her, holding lectures, doing interviews, maybe some sightseeing and of course, preparing for the grand finale; the prize-giving ceremony and the banquet held on 10 December.
Ever since the Nobel Prize winners were announced in October, Ada Yonath’s phone has been ringing a lot and meeting reporters has almost become her daily work, she says and laughs. Despite the fact that she probably has answered the questions I ask her several times before she is passionate and engaging when she tells me about the research that led to the Nobel Prize.
“It is a great honor and recognition of my work to receive a Nobel Prize and I was very excited and happy when I got the telephone call from Sweden,” she says. “However, recognition should not be a scientist’s everyday goal, there must be a passion for science and a dedication and determination beyond prizes and recognition. Also, you should not be afraid to fail.”
Perhaps this passion and determination is what made her go on and continue working on the mapping of the ribosome structure although colleagues were skeptical.
It is an interesting story how Ada Yonath first began to work on the ribosome structure. At the end of the 1970’s she had a bicycle accident. She suffered from a brain concussion and had to rest from work for quite a long time.
“I took the opportunity to read a lot and I particularly took a liking to an article describing the polar bears and what happens when they hibernate. In order to start their metabolism in spring there must be some kind of arrangement in the ribosomes. I got the idea that the ribosomes can be packed in an orderly way, that there is a way to preserve active ribosomes, by close-packing them,” she says.
By studying extremely durable bacteria from the Black Sea, which could tolerate both high temperatures and high salt amounts, she found a way to preserve their activity and integrity during crystallization.
In 1987, Ada Yonath and her colleagues developed a cryogenic technique, cryo bio-crystallography, a technique which has contributed a lot to the mapping of the ribosome structure and also to the entire field of structural biology. Before, only a few hundred protein structures were determined, and after 2000, 27 000 have been added.
She cracked the ribosome structure
Mapping and understanding the structure of the ribosome is an important and fundamental achievement of our time in our efforts to understand more about ourselves and where we come from.
“The ribosomes are the machinery of the cells. They get their instructions from the genetic code and operate chemically to produce proteins, i.e. translate the genetic code into proteins. The ribosomes work fast and accurately and they proofread their results and protect the proteins until they are capable of protecting themselves,” explains Ada Yonath.
From her work, she showed that the ribosome is a ribozyme that places substrates in stereochemistry suitable for peptide bond formation and for substrate mediated catalysis.
“We used X-ray crystallography to map the position for each and every one of the hundreds and thousands of atoms that make up the ribosome and finally, after almost 20 years, we had the complete three-dimensional atomic structure of the ribosome mapped,” she says
This was the most joyful and exciting moment ever in Ada Yonath’s career she says and her eyes sparkle. She had started the work in 1979 and the final complete structures were published in 2000 and 2001.
“I doubted many times that we would succeed, but we finally did,” she says and smiles.
The mapping of the structure has, and will, lead to several important applications and new discoveries. The most concrete and perhaps most clinically important application is the development of new antibiotics. One of the most central medical challenges of the 21st century is the increasing antibiotic resistance among bacteria. There are today super bugs like MRSA and over a third of all bacteria in hospitals have become resistant.
“Over 50% of all antibiotics target the ribosome and if it is effective it should attach to structures that are only present on the bacteria and not the affected patient. Usually, the antibiotic only has one attachment site and resistance can occur quite easily. We try to find new sites on the ribosome where the antibiotics can attach. The three-dimensional models show how different antibiotics can bind to ribosomes,” says Ada Yonath.
“We have investigated the modes of binding of over a dozen antibiotics by crystallography, elucidated the structural basis for their actions as well as their selectivity, and illuminated possible pathways for acquiring resistance by pathogenic bacteria.”
Ada Yonath’s work might also explain the origin of life.
“Many believe that life began with RNA and a machinery consisting of RNA. We have found evidence of this kind of structure in the most active site of the ribosome,” she says.
A curious lady
Ada Yonath is at present 70 years old and she is the head of a laboratory at the Weizmann Institute of Science in Rehovot, south of Tel Aviv in Israel. She is still very involved in research.
“Growing up in Jerusalem I was very curious and fond of experiments early on. Once I broke my arm falling down from our balcony when I was trying to measure the height of it,” she recalls.
She received her PhD in X-ray crystallography in 1968 from the Weizmann Institute and did postdoctoral work in the US, at the Massachusetts Institute of Technology (MIT) and the Carnegie Mellon University during 1969-1970. In 1970, she established a laboratory at the Weizmann Institute, and for nearly a decade it was Israel’s only protein crystallography laboratory. After a sabbatical year as visiting professor at the University of Chicago she headed a research unit at the Max Planck Institute in Hamburg for 17 years, in parallel to her activities at the Weizmann Institute. Ada Yonath is the first female Nobel Prize laureate in Chemistry in 45 years and the ninth Israeli to be awarded a Nobel Prize.
Ada E. Yonath
Born: 1939, in Jerusalem
1962 Bachelor’s Degree in chemistry, Hebrew University of Jerusalem
1964 Masters Degree in biochemistry, Hebrew University of Jerusalem
1968 PhD in X-ray crystallography, Weizmann Institute of Science
1969 Post doc, Carnegie Mellon University
1970 Post doc, MIT
1970 Established the protein crystallography laboratory at the Weizmann Institute of Sciences
1979-1984 Group leader at the Max Planck Institute for Molecular Genetics in Berlin
1977-1978 Visiting professor at Chicago University
1986-2004 Head of a research unit at the Max Planck Institute in Hamburg in parallel to her research activities at the Weizmann Institute
Family: daughter and granddaughter
Curiosa: The first Israeli biologist to work with NASA, sending research material into outer space. She contributed her expertise to 12 NASA missions.
Photo Credits: iucr.org