Martin Egli, the Richard N. Armstrong, Ph.D. Professor of Innovation in Biochemistry and a professor of biochemistry at the School of Medicine Basic Sciences, delivered a Kairos Lecture on May 28.
The chair of the Department of Biochemistry, David Cortez, introduced Egli. Cortez gave a brief biography and touched on Egli’s accomplishments, which include his pioneering of nucleic-acid crystallography methods and solving of ultra-high-resolution structures of canonical and unusual forms of DNA and DNA/RNA hybrids. Egli’s work, which has resulted in over 300 publications and two influential nucleic acid textbooks, has advanced strategies to stabilize RNA for therapeutic applications, including siRNA. He has received major honors and extensively served his department and the university.
In his lecture, “RNA Structure, Etiology and Re-Engineering Into siRNA Therapeutics,” Egli discussed how the 2’-hydroxyl group on RNA’s sugar (ribose) increases chemical and conformational diversity, affecting stability, function, and enabling more varied base pairing than DNA. He explained that, as RNA has a vast folding landscape and limited 3D structural and sequence data, structure prediction hasn’t reached a transformative “RNA AlphaFold” stage, an observation made in reference to AlphaFold’s role in revolutionizing protein structure prediction.
In investigating why biology uses ribose and not other sugars, Egli and other researchers found alternative base-pairing systems, revealing that ribose is uniquely well-suited for nucleic acid structure and function. These alternative systems, referred to as xeno nucleic acids, also provide practical modifications to improve RNA therapeutics by enhancing stability, tuning protein interactions and delivery, and reducing off-target effects.
The lecture concluded with a round of questions from the audience and a reception for attendees to mingle at.
About the speaker:
Egli obtained a diploma in chemistry and a doctorate in crystallography and stereochemistry from ETH Zürich. After a postdoc in structural biology at the Massachusetts Institute of Technology and a lectureship at ETHZ, he spent five years as an assistant professor at Northwestern University before moving to Vanderbilt University in 2000. He has also been a visiting professor in the departments of chemistry at Seoul National University and the University of Oxford.
His research interests include the 3D structures of DNA, RNA, and artificial pairing systems like xeno nucleic acids, chemical modification and conjugation of siRNA therapeutics, trans-lesion polymerase–DNA adduct interactions, the water structure around macromolecules, structure-function studies of the cyanobacterial circadian clock, the mechanism of steroidogenic cytochrome P450s, and structure-activity relationships of enzyme-ligand interactions.
Kairos Lectures take place throughout the year on the fourth Thursday of the month in 1220 Medical Research Building III.
