Dr. Shira Weingarten-Gabbay

Dr. Shira Weingarten-Gabbay, a postdoctoral researcher with Dr. Pardis Sabeti at the Broad Institute (Cambridge, USA) and Dr. Charles Rice at the Rockefeller University (New York, USA), has taken on the daunting task of illuminating the “dark matter” of viral proteomes. During the first part of her postdoctoral studies, Dr. Weingarten-Gabbay discovered “potent T-cell targets that originated from non-canonical ORFs in the SARS-CoV genome. Strikingly, some of the non-canonical epitopes triggered stronger T cell responses in COVID-19 patients, yet they remained unknown for the first 18 months of the pandemic.” This finding underscored the importance of examining viral genomes for as-yet-undiscovered actively translated regions to gain a full understanding of antiviral immunity, thereby forming the basis of her research program.

Dr. Weingarten-Gabbay was first drawn to the world of systems biology as a graduate student with Dr. Eran Segal at the Weizmann Institute of Science (Israel), where she used massively parallel reporter assays to identify new human and viral Internal Ribosome Entry Sites (IRESes). She recalled, “the Segal lab was an amazing environment for acquiring skills in systems biology and computational biology needed to embark on this mission. Eran’s mentorship and the brilliant colleagues at the Segal lab have shaped how I approach biological questions to date.” Following her graduate studies, she sought to combine her background in systems biology with postdoctoral training in virology. “The Sabeti lab had a rare combination of teams working on developing high-throughput approaches to functionally characterize the human genome on one hand, and ground-breaking research in viral genomics on the other hand.” She also highlighted the importance of seeking out supportive mentors, describing Dr. Sabeti as “a true role model who is deeply passionate about providing a nurturing place for postdocs to grow and develop their independent research program.”

Dr. Weingarten-Gabbay considers herself very fortunate to have benefited from rigorous, diverse training and as such, is quick to note the importance of all stages of scientific training. She advises trainees to “embrace [each step] and make the most out of it, as you will not get this time back!” She recommends that undergraduate students take advantage of opportunities to “learn the fundamentals in mathematics, statistics, physics, and organic chemistry. While you may not use this knowledge in your day-to-day research, it will be invaluable for in-depth understanding of your biological questions and interpretation of your findings.” Building on this, she believes that the key to innovative research is when people bring different perspectives into a new field. For trainees who choose to transition fields for their postdoctoral research, she suggested to “remove the phrase ‘hit the ground running’ from your vocabulary. Remember that postdoctoral training is a marathon! Redefine productivity as the sum of your achievements over time and not by how many hours you spend at the bench. This is the time to develop your research program and get to know your field.” Dr. Weingarten-Gabbay recognizes that transition periods can be difficult and recommends “choosing a supportive mentor and lab that will prepare you for the next independent step in your career.”

“Remember that postdoctoral training is a marathon! Redefine productivity as the sum of your achievements over time and not by how many hours you spend at the bench.”

Like many current trainees, Dr. Weingarten-Gabbay encountered difficulties during the COVID-19 pandemic that impacted her postdoctoral training. “Our lab was shut down for months and my main project took a hit,” she shared. “I was a young mother to a 1-year-old with no daycare, and I was just starting a new project on SARS-CoV-2 in the very unusual circumstances of conducting research while the people of Boston were sheltering in place.” She credited the support that came from “being frank with my spouse, my mentor, and my collaborators. Keeping communication channels open and actively seeking advice was the key.” But despite the frustrations of COVID-19, Dr. Weingarten-Gabbay reflected on the unique opportunities the pandemic afforded virologists. “Joining the global community to research SARS-CoV-2 during this critical time in history was one of the most rewarding experiences in my career.” She also noted the importance of establishing collaborations, especially regarding COVID-19 research. “My research spans various fields, including virology, systems biology, proteomics, and immunology. I wholeheartedly believe that I could not pursue it if it weren’t for the partnerships with talented scientists in these fields and learning from their vast knowledge.”

Understanding the importance of establishing global connections, another highlight of Dr. Weingarten-Gabbay’s career has been co-founding the Systems Virology Journal Club with her colleague Dr. Bill Schneider from the Rice lab. “The journal club showcases cutting-edge research at the interface of virology and systems biology,” she shared. “But even more importantly, I have had the opportunity to get to know many peers from across the globe who share my passion for this fascinating emerging field.” Dr. Weingarten-Gabbay has also found a supportive, engaging community within the RNA Society, and looks up to many Society members across generations. “Among her many contributions to RNA biology, Joan Steitz identified ribosome footprints using RNA protection assays in the late 1960s. This discovery paved the way for the development of ribosome profiling by Nicholas Ingolia and Jonathan Weissman [which] completely revolutionized our understanding of translated regions in many organisms. I believe it’s a beautiful demonstration of how combining curiosity-driven basic science with high-throughput methods can lead to ground-breaking scientific discoveries.”

In recognition of her significant advances in systems biology and virology, Dr. Weingarten-Gabbay was honored at this year’s RNA Society meeting with the Eclipse Award for Innovation in High Throughput Biology. Inspired by this, she plans to continue using systems biology tools to discover the secrets hidden within viral genomes. Her current work involves “developing high-throughput methods that combine ribosome profiling with a synthetic oligonucleotide library to experimentally measure translated region in approximately 700 human viruses. We recently uncovered thousands of new viral ORFs, and I’m very excited about using this wealth of data to shed light on the function of “hidden proteins” across various aspects of the viral life cycle.”

Dr. Weingarten-Gabbay’s favorite RNAs are positive-strand RNA viruses, which “serve not only as the virus’s genome, but also as the template for replication and protein translation. Consider the diverse properties required to support each of these functions. How is all this information encoded within a single RNA molecule?” You can reach her (and discuss the wonders of viruses) on social media @WeingartenShira and find out more at shiraweingartengabbay.com.