The rockefeller university

Event Details

Type

Evnin Chemical and Structural Biology Seminar Series

Speaker(s)

Bryan Dickinson, Ph.D., Professor, Department of Chemistry, The University of Chicago

Speaker bio(s)

Abstract: Discovering molecules that precisely recognize biological targets is foundational to both basic science and medicine, yet existing platforms remain constrained by tradeoffs in speed, cost, and throughput. To address this, the Dickinson laboratory developed PANCS, an in vivo evolution platform that couples molecular recognition directly to phage replication in bacterial cells, enabling the screening of billions of protein and peptide variants per week with selection fidelity inaccessible to traditional in vitro approaches. Using PANCS, we have identified high-affinity miniprotein binders to therapeutically relevant targets with superior specificity, and generated rich fitness landscape data suitable for training machine learning models that accelerate discovery. Extending this platform, they developed new in-cell selection strategies to discover peptide-based molecular glues — bifunctional molecules that induce protein proximity — revealing a novel cooperativity mechanism that overcomes key limitations of existing proximity-inducing molecules. Together, these advances position in vivo evolution, augmented by artificial intelligence, as a generalizable and powerful engine for molecular discovery and therapeutic innovation.

Open to

Tri-Institutional