Antibiotics have transformed our ability to treat many infectious diseases that were killers only a few decades ago. But with increasing use, many bacteria are becoming resistant to the most commonly prescribed antibiotic treatments – so much so, that resistance to antibiotics has become one of the world’s most pressing health problems. There is therefore a need to develop new and potent antibiotics with novel modes of action. To design such drugs, however, it is very important to solve the 3-D crystal structures of the bacterial target proteins, since they are the templates with which the drug interacts, just as a key fits into a lock.
This has been, for many years, the aim of Weizmann Institute graduate Prof. Osnat Herzberg, who continues her endeavor at the Center for Advanced Research in Biotechnology (CARB) of the University of Maryland, USA.
For her Ph.D. research, Herzberg chose to specialize in protein X-ray crystallography. “Although structural biology was a relatively young subject, many great scientific breakthroughs were being made, and I just had to be in the forefront of this field,” says Herzberg.
Herzberg received her master’s degree in geo-isotope research from the Weizmann Institute in 1976 and then, under the guidance of Prof. Ada Yonath and Prof. John Moult (a visiting scientist at the time), went on to pursue her Ph.D. studies in what was then the Institute’s Structural Chemistry Department, receiving her degree in 1982. Her research focused on understanding the structural basis for the action of beta-lactamases – enzymes produced by some bacteria that give them resistance to certain antibiotics such as penicillin. During her postdoctoral studies, carried out at the University of Alberta, Edmonton, Canada, she eventually managed to solve the structure of the enzyme in 1987.
Among a number of research topics that she pursues at CARB, where she has now been for almost 20 years, Herzberg maintains her interest in determining the structure of beta-lactamases as a means of understanding their function and mechanism of action. But something about the Weizmann Institute keeps drawing her back. Herzberg jumped at the opportunity to work in the Weizmann Institute’s Israel Structural Proteomics Center, headed by Prof. Joel Sussman, which is equipped with state-of-the-art instumentation for protein production, crystallization and 3-D structure determination, and develops high throughput approaches for determining the 3-D structures of human protein targets of medical importance. For two three-month periods in 2004 and 2005, she took sabbatical leaves, supported by the Weizmann Institute’s Weston Visiting Professorship and the Helen and Milton A. Kimmelman Center, respectively, in which she immersed herself in “hands-on” bench work.
“I felt the best way to really understand and appreciate the work carried out by my students was to place myself in their shoes, and I am now able to provide better guidance and to adopt innovative techniques that I myself learned at the Weizmann Institute.”
The Israel Structural Proteomics Center is funded by the Ministry of Science and Technology; the EU Structural Proteomics in Europe (SPINE) project; and the Divadol Foundation for Technology Development.