Affiliations: Structural Biology Department, Weizmann Institute of Science
Biography
Dr. Shalev Ben-Ami is a post-doctoral fellow at the Weizmann institute of Science in Israel, working in Prof. Ada Yonath’s research group on structural and biochemical aspects of antibiotic resistance. Dr. Shalev Ben-Ami holds a Ph.D in Chemistry from the Technion Institute of Technology in Israel, focusing on structural investigations of eukaryotic and prokaryotic ribosomes for rational development of ribosome-targeted drugs aimed at treatment of bacterial and protozoan infections and nonsense-mediated genetic disorders. For her work, Dr. Shalev Ben-Ami has received the prestigious Chateaubriand fellowship awarded by the French ministry of science as well as the Schulich prize for scientific excellence among research students, the Klartag memorial prize for excellence in biochemistry research and the Sir Charles Clore Fellowship for her postdoctoral studies.
Abstract
The Ribosome as a Drug Target: Insights from Structural Investigations - Towards Structure Based Drug Design
Moran Shalev Ben-Ami, Charles L. Jaffe, Noam Adir and Timor Baasov
Ribosomes are giant ribonucleoprotein machineries residing within all living cells that translate the genetic code unto protein, thus play an important role in cellular maintenance and viability. The key function and abundance of these machineries makes them an effective target for various therapeutic approaches. The most prominent example of this is the bacterial ribosome which has been the target of a large assortment of clinically used antibiotics for the past 4 decades. In recent years, small molecules that target eukaryotic ribosomes were suggested as novel therapeutic approach for the treatment of parasite related infections and nonsense-mediated genetic disorders. Nevertheless, although recent structural and biochemical studies shed light on the mechanisms of action of such compounds in bacterial ribosomes, the molecular details underlying their differential effects in eukaryotes are still unclear. Our research was dedicated to the biochemical and structural investigation of the differential selectivity of a large family of therapeutic compounds, called aminoglycosides, in eukaryotic ribosomes. Our obtained results revealed aminoglycosides’ mechanisms of action in eukaryotic ribosomes and highlighted the molecular attributes important for their selective effects towards distinct species. These studies set the ground for the structure based design of novel and highly specific derivatives that are now being sought as potential therapeutics for parasite related infections such as leishmaniasis as well as for the treatment of genetic disorders.
