Peter G. Schultz - 2025 Welch Awardee Lecture

"Synthesis at the Interface of Chemistry and Biology"

Peter Schultz, Ph.D., is a Professor of Chemistry, Chief Executive Officer and the Sam Skaggs Presidential Chair at Scripps Research. Schultz has made many seminal contributions to the fields of chemical and synthetic biology, including the development and application of methods to expand the genetic code of living organisms, the discovery of catalytic antibodies, and the development and application of molecular diversity technologies to address problems in chemistry, materials science and medicine. The co-author of more than 650 scientific publications, he has trained over 300 graduate students and postdoctoral fellows, many of whom are on the faculties of major research institutions around the world. Schultz earned his undergraduate (summa cum laude) and doctoral degrees at the California Institute of Technology. After postdoctoral studies at the Massachusetts Institute of Technology, he joined the faculty at the University of California, Berkeley in 1985, where he was a chemistry professor, a principal investigator at the Lawrence Berkeley National Laboratory and a Howard Hughes Medical Institute investigator. He joined Scripps Research in 1999 and was appointed chief executive officer in 2016. Schultz has founded nine biotech/tech companies that have pioneered the development and application of new technologies to challenges in human health and materials science. In 1999, he founded the Genomics Institute of the Novartis Research Foundation, serving as its director for more than 10 years. In 2012, he established Calibr, a non-profit biomedical research institute designed as a new model to accelerate the discovery of innovative medicines, and which is now an operating division of Scripps Research. Schultz has overseen efforts that have led to some 30 programs being advanced into clinical trials or to approval.

Abstract: “Synthesis at the Interface of Chemistry and Biology”

Chemical synthesis as a tool to control the structure and properties of matter is at the heart of chemistry from the synthesis of fine chemicals and polymers to drugs and solid-state materials. But as the field evolves to tackle larger and larger molecules and molecular complexes, the traditional tools of synthetic chemistry become limiting. In contrast, Mother Nature has developed very different strategies to create the macromolecules and molecular systems that make up the living cell. Our focus has been to ask whether we can use the synthetic strategies and machinery of Mother Nature, together with modern chemical tools, to create new macromolecules, and even whole organisms with properties not existing in nature. This presentation will focus on one such example which involves reprogramming the complex, multicomponent machinery of ribosomal protein synthesis to add new building blocks to the genetic code, overcoming a billion-year constraint on the chemical nature of proteins. This methodology exploits the concept of bioorthogonality to add unique codons, tRNAs and aminoacyl-tRNA synthetases to cells to encode amino acids with physical, chemical and biological properties not found in nature. As a result, we can make precise changes to the structures of proteins, much like those made by chemists to small molecules and beyond those possible by biological approaches alone. This technology has made it possible to probe protein structure and function in vitro and in vivo in ways heretofore not possible, and to make therapeutic proteins with enhanced pharmacology.

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