Quick Q&A with NCBI’s Evolutionary Genomics Research Group

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Quick Q&A with Svetlana Shabalina, Yuri Wolf, and Michael Galperin
Question Svetlana Shabalina, PhD Yuri Wolf, PhD Michael Y. Galperin, PhD
headshot of Svetlana Shabalina  casual headshot of Yuri Wolf  
In lay terms, what is the focus of your NLM research?
My research focuses on the comparative analysis of the transcriptome, the set of all RNA sequences (transcripts) in a cell. I study the complexity and diversity of the mammalian transcriptomes, in which multiple alternative transcripts can be produced from a single gene and their functions are largely unknown.

The goal is to understand how the transcriptome evolves and works in various cells, tissues, and conditions, focusing on non-coding RNAs and alternative transcripts in mammals.

My research interests also include understanding how RNA molecules fold after being transcribed and processed, associating genomic variations with the architecture and function of the human transcriptome, and estimating the rate at which populations accumulate mutations.

Genomes of living organisms constantly change, acquiring mutations, gaining and losing genes, and rearranging their DNA. I quantify these changes, look for emerging patterns in the data, and try to infer the underlying mechanisms and relationships. I look at bacterial genomes to try to catalog and analyze proteins whose functions still remain unknown. I also study how bacteria sense environmental and intracellular parameters and use this information to adjust their metabolism and make lifestyle decisions (run—stay—attack the host—grow a biofilm).
Why is your research significant, in your opinion? Our efforts are increasingly focusing on comparative analysis and understanding the functions of transcribed non-protein-coding regions under different physiological conditions.

Growing evidence suggests that the architecture of the transcriptome in mammals is important for many vital processes such as cell growth, survival, and DNA damage in cancer and other diseases.

These concepts are important not just for understanding genomics and the biology of life, but also for medicine. For example, how do human genome variations influence the alternative transcripts architecture and function through the modification of RNA secondary and 3D structures? The answer might have a medical application because of the associations between many different diseases and specific gene and transcript variations.

The whole living world we deal with is, ultimately, a result of billions of years of evolution at the genomic level and what we see now bears an indelible imprint of history. By trying to unravel the twisting paths of the past, we try to improve our understanding of life now. It is important to understand what makes the bacteria feel (un)comfortable. For example, how could we dissuade them from harming their human hosts?
What or who inspired you to pursue your career? Ever since childhood, growing up in the Ural Mountains of Russia, I was curious about how living organisms adapted to nature and the mechanisms through which different organisms could survive in dangerous and severe climate conditions. My parents had an incredible love for nature and instilled the same in me. I grew up with a connection to nature, which inspired me to pursue science and research. Later when I moved to Moscow, I met dedicated scientists and enthusiastic researchers in mathematics, physics, biology, and medicine. The scientific community has always felt like home. Somehow I knew I wanted to be a biologist since the age of five. Books of natural history were always my favorites. In my early teens, I read about the chemical mechanisms of enzymatic activity, and since then, understanding life at the molecular level has been the focus of my interest. My mother spent many years working on a drug or vaccine against diphtheria using the trial-and-error approach. (This was long before the current DPT vaccine.) I loved the general idea but felt that understanding bacterial physiology could allow us to do better.
How did you get started in your career? My career began when I was a student at Kolmogorov’s special boarding school for advanced studies in math and physics (affiliated with the Moscow State University). There, I studied math, physics, and computer science and learned how to pursue a scientific career. I got my master’s degree in genetics from Moscow State University and my doctorate in computational biology. I got my professional start at the Institute of Mathematical Problems in Biology, which is part of the Russian Academy of Science. I later moved to the Evolution and Ecology Department at Cornell University. I joined NCBI in 1999. I spent a year between high school and college working as a technician with field biologists. There I got my first experience turning quantitative data into biological insights. Then, while an undergraduate, a combination of lucky circumstances and some good advice led me to what is now called computational biology, where I have stayed ever since. I started my undergraduate research at the Moscow State University as an experimental biochemist studying how various bacteria store and use the energy of the proton-motive force. This was a terrific group of people who are now spread from Boston to Winnipeg to Jerusalem. Then I got interested in the regulation of these processes and have kept this focus ever since.
What really gets you jazzed about science and research? The most attractive part of any study is solving a puzzle or finding an answer to an open-ended question. The solution could be expected or may be completely unpredictable, but the process of looking for the answer is engaging and fun. Unsatisfied curiosity is one of the strongest driving forces in research.

The second very important component of scientific life, especially in interdisciplinary fields, such as bioinformatics and computational biology, is the collaboration and communication with dedicated researchers and colleagues of various educational and vocational backgrounds. I have many collaborators with different areas of expertise who have helped me with new techniques, methods, and most importantly, discussion of new questions and hypotheses.

Seeing numbers turning into trends and then into understanding is a thrill that has kept me going all these years. With all the genome sequences, we still have a very vague understanding of bacterial signaling and cannot use this knowledge to ward off syphilis, Lyme disease, MRSA, and other nasty infections.
If you weren’t doing what you’re doing now, what else might you be doing? When I was a child, I tried hard to answer this question. I came up with two choices—I thought I would be happy as a mathematician or as a doctor. This might explain why I work in the field of computational biology, combining a bit of each profession. Marine biologist if not a computational biologist, geologist if not a biologist, engineer if not a scientist, metalworker if having a blue-collar job. I could be a science teacher, a librarian, or a political consultant.
Tell us something surprising about yourself. I do not like to read newspapers, especially political news. Instead, I usually go through the biotechnological news, new releases from the FDA and clinical trials, and the daily news on GenomeWeb. I realized long ago that this focus not only helps me improve my knowledge of the field of medicine, it keeps me positive and focused. According to a former postdoc from our group, I tend to explain situations at work using quotes from Winnie-the-Pooh. I thought of going to med school but almost fainted at the sight of blood. Having to wear a tie didn’t seem that attractive either. My college life was largely dedicated to table tennis and Frisbee.

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