Prof. Schraga SchwartzBy Dr. Sara Zaccara  Dr. Schraga Schwartz is a professor and group leader at the Weizmann Institute of Science in Rehovot, Israel. Dr. Schwartz obtained a B.Sc. in Medicine from Tel-Aviv University, where he also finished his PhD with Dr. Gil Ast. He completed his post-doctoral training first with Dr. Rotem Sorek at the Weizmann Institute and then with Dr. Aviv Regev and Dr. Eric Lander at the Broad Institute in Boston, USA. During his research career, Dr. Schwartz has revolutionized our knowledge of RNA modifications. RNAs possess chemical modifications that expand their vocabulary beyond adenosine, guanosine, cytidine and uridine, and these modifications serve crucial roles in ensuring RNA structure, dynamics, function and regulation. By developing precise experimental methodologies coupled with analytic pipelines, Prof. Schwartz and his group have quantified, mapped, and characterized an array of RNA modifications and increased our understanding of their functions. Prof. Schwartz's path to becoming a leading RNA modification researcher was not straightforward. After finishing his PhD with Prof. Gils Ast, Dr. Schwartz returned to medical school and started a rotation in an internal medicine ward. He explained, "In practice, as is true for so many aspects of my academic career, chance played a significant role. I quickly realized that a medical career and I were not meant to be, so after a bit less than a year, I decided to quit the medical school. Given that I hadn't really planned for a post-doc abroad, I thought I'd join a local lab in Israel for a year, to give myself some time to figure out where to do a post-doc. Earlier, I heard an exciting talk from Dr. Rotem Sorek, from the Weizmann Institute, about his endeavors to sequence the first microbial transcriptomes. So, I applied and joined his lab for a year. One of the dimensions I explored in Dr. Sorek's lab was whether or not we could find evidence for A to I editing events in microbes." In parallel, he was also working on other RNA modifications, such as N⁶-methyladenosine (m6A) and 5-methylcytosine (m5C). "By the time the year was up, and I was ready to begin my post-doc at the Broad Institute with Profs. Aviv Regev and Eric Lander, I was completely hooked on RNA modifications."
In remembering one of his recent scientific breakthroughs, Prof. Schwartz described the "thrilling moment in science sitting together with my post-doc, Dr. Aldema Sas-Chen, and looking together for the first time at RNA acetylation maps that we had acquired for an archaeal hyperthermophile. The background to this is that, working together with Jordan Meier from the NIH, we had developed an approach for mapping of acetylated cytidine (ac4C), in the hope of characterizing acetylation sites in human mRNAs. The method worked very well, but to our great consternation, we were unable to find any evidence for the existence of acetylated sites beyond its known repositories in tRNA and rRNA. We tried looking at other eukaryotes or bacteria, and again - couldn't find anything. We got desperate, at which point we applied our approach to an archaeal hyperthermophile, Thermococcus kodakarensis, which in all honesty I had never even heard about before. Anyway, Aldema and I were sitting together, and the data had just gotten in, so we quickly aligned it and loaded it in a genome browser to eyeball it a bit. Amazingly, a super-quick glance made it clear that acetylations were all over the place in this organism. We saw it on dozens of sites on basically any class of RNA - mRNAs, tRNAs, rRNAs. It was clear that whatever was going on, it was unique and quite unprecedented, and we were seeing this for the first time." He is very excited about "the role of RNA modifications in modulating the structure and function of ribosomes. For years it was assumed that all ribosomes within our cells are the same. However, in recent years it is becoming clear that ribosomes, even within the same cell, can be different from each other, in terms of sequence, protein composition, and - of particular interest to us - RNA modifications." Prof. Schwartz believes that helping trainees to become independent scientists is an important aspect of his role as a mentor. He said, "A challenge I continuously face with my trainees is balancing their independence with my supervision. On the one hand, I feel that it is critical to instill a sense of independence in my trainees and to empower them to pursue any scientific questions that they find to be of interest or that they are being driven into based on their science. On the other hand, I often also have my thoughts regarding the merits of choosing a particular direction, or the likelihood that it will prove to be successful or insightful. Whether and when to voice my opinion or to remain silent is an ongoing dilemma." He relies heavily on his experiences as an early career scientist as he guides his trainees, "I feel that I've learned by example. I've been privileged to have super-supportive and generous mentors, who were able to establish wonderful working environments, and did their utmost to support my success. I am deeply grateful to them, and I try to establish a similar environment in my lab." When asked about his key advice for trainees, Dr. Schwartz remarked, "A main recurrent theme I am seeing in my own trainees is a tendency to accept published literature as 'truth'. I think it is crucial to understand that science is pursued by people. And just as we can, at times, err in our thinking or interpretation, the same may hold for published literature, even in the best of journals. Be critical - both of your own results and of those reported by others." In acknowledgement of his contributions to RNA science, Prof. Schwartz was named the winner of the 2021 Early-Career Research Award. "I am very grateful to the RNA Society for this recognition. In general, I feel fortunate to be conducting science in an area that is brought together by such an active society. One of the challenges of a career in science is that significant parts of it are conducted, to a large extent, in isolation - within the four walls of one's lab or office. Being able to receive such recognition from the broad community is both motivating and uplifting." At the moment his favorite RNA molecules are the ribosomal RNAs. "They are beautifully and intricately structured, they interact among themselves via a delicate and intimate dance, they are catalytically active, and they lie at the molecular center of all forms of life." Twitter: @schragaSchwartz |