Ada Yonath
Nobel Prize in Chemistry 2009
Wednesday, 4th February, 3 pm
Auditorium of the FCT-UNL Library
Department of Structural Biology, Weizmann Institute, Rehovot, Israel
http://www.weizmann.ac.il/sb/faculty_pages/Yonath/
http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2009/yonath-facts.html
Resistance to Antibiotics and Preserving the Microbiome
Striving to understand the fundamental process of the translation of the genetic code, a basic and most important process of life, we developed innovating methodologies and determined the structure and deciphered its mode of function of the ribosome, the universal cellular “factory” that performed the formation of the proteins (the cell workers) according to the genetic code. Owing to their vital role in cell life, the ribosomes are paralyzed by many antibiotics. Consequently, once we understood the basic issues in ribosome function, we focused on the inhibitory actions and synergism pathways of almost all ribosomal antibiotics. The results of these studies indicated the principles of differentiation between patients and disease carrying bacteria, suggested mechanisms leading to bacterial resistance and paved ways for improvement of existing antibiotics as well as for the design of advanced therapeutics capable of minimizing antibiotics resistance.
However, as species specific diversity was detected in susceptibility to infectious diseases and in developing specific resistance mechanisms, we extended our structural studies to ribosomes from genuine pathogens. By determining the high resolution structures of the first ribosomal particle from a genuine multi-resistant pathogen with several antibiotics, we identified subtle, albeit highly significant structural elements in the antibiotics binding pockets that can account partially or fully for species specificity in resistance; revealed elements of species specificity and paved ways for improvement of existing antibiotics. Furthermore these studies and provided structural tolls for the design of “species specific antibiotics”, each of which targeting a specific bacterium, thus preserving the microbiome including the gut flora.
Biography
Professor Ada Yonath was born in Jerusalem and earned her B.Sc (1962) and M.Sc. (1964) degrees at the Hebrew University of Jerusalem. In 1968, she completed her Ph.D. at the Weizmann Institute of Science. She continued postdoctoral studies at Carnegie Mellon University and at the Massachusetts Institute of Technology, where she first learned about protein crystallography. In 1970, she returned to the Weizmann Institute and established what was, for almost a decade, the only protein crystallography laboratory in Israel.
Dr. Ada Yonath is the pioneer of ribosome crystallography. She began this work in the late 1970s, long before most others thought it possible to crystallize such a large, irregular structure. In 1980, she created the first ribosome crystals from thermophilic and halophilic bacteria. Dr. Yonath was also a pioneer in the use of cryocrystallography--flash-freezing crystals--to minimize damage caused by intense X-rays. Dr. Yonath was the first to observe that the ribosome is riddled with internal channels and chambers, including a cavern that hosts translation and a tunnel that protects newly synthesized proteins. These findings remained controversial for nearly a decade until they were confirmed by cryo-electron microscopy.
Dr. Yonath also used controlled heating and an mRNA analog to trigger protein biosynthesis in ribosomal crystals. She then preserved the activated ribosomal crystals using various chemical compounds. In 2000, she published the 3.3 Angstrom structure of the small (30S) ribosomal subunit.
Among many other awards and honors, in 2009, she received the Nobel Prize in Chemistry along with Venkatraman Ramakrishnan and Thomas A. Steitz for her studies on the structure and function of the ribosome, becoming the first Israeli woman to win the Nobel Prize out of ten Israeli Nobel laureates, the first woman from the Middle East to win a Nobel prize in the sciences, and the first woman in 45 years to win the Nobel Prize for Chemistry.