RNA Innovation Seminar: Nils G. Walter, Ph.D., Co-Director, U-M Center for RNA Biomedicine

“Single molecules come into focus: From bacterial riboswitches to mammalian cellular phase separation”
Nils G. Walter, Ph.D.

Co-Director,
U-M Center for RNA Biomedicine
Francis S Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry,
U-M LSA

Abstract:
At least 75% of the 3 billion base pairs of the human genome are transcribed into RNA, but the vast majority of these transcripts do not code for proteins but rather for “non-coding” RNAs (ncRNAs), many of which remain uncharacterized in terms of their structure and function. Currently, more than 80,000 unique ncRNAs have been identified in human cells alone, suggesting that for a long time we have underestimated the intricacies involved in human genome maintenance, processing, and regulation by neglecting this far-reaching “RNA World.” Nature and modern nanotechnology likewise employ nanoscale RNA machines that self-assemble into structures of complex architecture and functionality. Fluorescence microscopy offers a non-invasive tool to probe, dissect and ultimately control these nanoassemblies in real-time. In particular, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range. Encapsulating the power of these recent technical advances, we have combined single-molecule and biochemical approaches to show that a central, adaptable RNA helix in the widespread manganese-sensing riboswitch functions analogous to a molecular fulcrum to integrate disparate signals for finely balanced bacterial gene expression control. We posit that many more examples of such intimate structural and kinetic coupling between RNA folding and gene expression remain to be discovered, leading to the exquisite regulatory control and kinetic proofreading enabling all life processes. On the more applied side, we are developing tools to study the liquid-liquid phase separation of RNA-protein granules involved in human pathologies.

Biography:
Nils G. Walter (photo by Michigan Photography) is currently the Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry in the College of Literature, Science and the Arts of the University of Michigan in Ann Arbor, Michigan. He cofounded and currently co-directs the Center for RNA Biomedicine at Michigan, now developing a thrust in RNA Therapeutics. His research interests focus on gene regulation by noncoding RNAs through the lens of single molecule techniques and applications in drug discovery.

In-person: BSRB, Kahn Auditorium / hybrid link

Links to learn more about Nils Walter and his work:
Nils Walter’s Faculty Page
Nils Walter’s Lab Page
Nils Walter’s Wikipedia Page