Professor Nils Walter

by Dr. Vidhyadhar Nandana

“I have a dream. I have been hooked on this dream ever since 30 years ago when I prepared for my German diploma exam by reading a chapter in Lubert Stryer’s Biochemistry textbook about catalytic RNAs” enunciated Dr. Nils G. Walter, a Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry at the University of Michigan. He heads the Single Molecule Analysis Group, which integrates cutting edge single molecule microscopy methods, biochemistry, and computational approaches to study dynamics of RNA molecules. Dr. Walter, originally from Germany, obtained his PhD with Nobel Laureate Manfred Eigen in 1995 at the Max Planck Institute for Biophysical Chemistry, Göttingen. He then gained four years of postdoctoral experience studying the biophysics of the hairpin ribozyme with Professor John M. Burke at the University of Vermont before becoming an Assistant Professor and starting his own research group in 1999 at the University of Michigan. He has received numerous awards for his work on RNA, including the RNA Society Mid-Career award in 2017.

RNA has been studied for over 100 years and is connected to the origin of life but “we are still limited in the mechanistic understanding of RNA functions by our incomplete picture of its kinetics,” according to Dr. Walter. He believes that single-molecule tools are perfect to measure these kinetics since they can explicitly observe and measure the folding and unfolding behavior of individual RNA molecules. Owing to his long-standing interest in single-molecule RNA analysis, Dr. Walter has been at the forefront of developing RNA single-molecule tracing techniques in live cells to probe gene regulation. He is the principal scientist in developing single-molecule recognition through equilibrium Poisson sampling (SiMREPS) for the amplification-free digital counting of single unlabeled RNA, DNA and protein biomarker molecules in complex biofluids, which laid the foundation of the biotech startup company, aLight Sciences Inc. Dr. Walter founded and is now directing University of Michigan’s Single Molecule Analysis in Real Time (SMART) Center and the Center for RNA Biomedicine, through which single molecule experiments and RNA research have been accelerated across the university.

Currently Dr. Walter is excited about a research idea that he is hopeful will address both the ongoing pandemic created by SARS-CoV-2 and the” shadow pandemic” of multi-drug resistant bacteria. Many riboswitches pause bacterial RNA polymerase right after they are transcribed, giving the RNA a longer time window to bind its ligand and manipulate the outcome of transcription and translation. Dr. Walter sees an opportunity here to find novel antibacterial agents directed against the RNA polymerase. By applying single molecule and cryo-electron microscopy, he is confident he will also gain insight into the RNA-dependent RNA polymerase of SARS-CoV-2. This work is currently funded by an NIH R35 Maximizing Investigators' Research Award (MIRA) award.

Dr. Walter took an unusual path into the US academic system. When he started applying for faculty positions, both his PhD and Postdoc mentors were either retiring or no longer fully research active. But the confidence instilled into him by his mentors, including his parents, helped Dr. Walter navigate the process, persevere, and become successful. Immigrating to the USA from Germany and adapting to the new culture was the biggest challenge that Dr. Walter encountered. That being said, he has always been prepared to take on challenges as he feels they build up self-confidence and broaden one’s perspective towards life. He emphasized the greater need for diversity and inclusion in science, which is a fountain of intellectual strength, and this is evident in his own research group’s diversity of people and his service for a decade as his department’s Graduate School Diversity Ally.

 “Be bold, be creative, and find your work-life balance to be your personal best. Science is often unpredictable – not to say “frustrating” – but any failed experiment can teach you almost as much as – or even more than – a successful experiment”.

Dr. Walter pointed out the importance of maintaining a balance between one’s professional and personal lives. He has two beautiful kids, and his family is one of his greatest joys. When asked about his good memories with the RNA society, “It was at RNA Society meeting in Banff a friend suggested to me to have kids”, Nils replied with excitement. “The COVID-19 pandemic has further driven home the need for a network of friends to lean on in times of personal or scientific challenges”. Dr. Walter remembers Olke Uhlenbeck’s Lifetime Achievement Award speech in 2006 as his favorite memory at an Annual Meeting of the RNA Society.

“RNA is at an amazing crossroads right now where we finally begin to see its sheer endless power in the form of non-coding, viral, and vaccine RNAs – RNA-seq, siRNAs, as well as CRISPR and RNA medicines are powerful tools”.

Dr. Walter’s favorite RNA is the hairpin ribozyme because he owes it his tenure in the academy. Connect with Dr. Walter on his lab website and on twitter @NilsWalterLab.