Research Seminar: Data-driven design of synthetic regulatory systems – Dr. Caleb Bashor

Abstract:

A central challenge in mammalian synthetic biology is learning how genetic design maps to cellular function. This problem spans a hierarchy of design scales that includes, genetic part sequence, their composition within, genomic and cellular context, and ultimately cell behavior. At each level, design is difficult because nonlinear and context-dependent interactions among genetic parts and host-cell machinery can obscure the relationship between engineering choices and functional output. A second challenge is scaling across the hierarchy: sequence-level models do not automatically predict circuit behavior, circuit measurements do not necessarily explain how circuits behave in different cellular contexts, and endpoint measurements often fail to capture the dynamic cell functions that matter for biotechnology and therapy. In this talk, I will describe how my lab is developing platforms that enable AI-driven design across this hierarchy. At the sequence level, genTU uses AI models to design transcriptional units from learned relationships between regulatory sequence and expression. At the circuit-composition level, CLASSIC enables large-scale pooled measurement of assembled mammalian circuits, generating datasets that train models to learn circuit design rules and identify optimized variants. At the cellular-function level, bannerFISH links circuit barcodes to dynamic single-cell phenotypes, enabling models to connect circuit architecture with temporal dynamics, cell-state transitions, and engineered cell behaviors in application-specific contexts. Together, these platforms establish a unified design/build/test/learn framework for mapping mammalian circuit design across scales. This work points toward AI models that can design regulatory programs with specified quantitative and dynamic behaviors tailored to specific biotechnology and therapeutic contexts.

Dr. Caleb Bashor‘s Biography:

Dr. Caleb Bashor is an Assistant Professor in the Departments of Bioengineering and Biosciences at Rice University. He is the Deputy Director of the Rice Synthetic Biology Institute and the Associate Director of the Rice Genetic Design and Engineering Center.