2025 AIChE Annual Meeting

(415j) Bringing Whole-Cell Models to Life: Advanced Modeling for Engineered Microbes

Authors

Gesse Roure, University of Colorado at Boulder
Biological cells are at the forefront of biomaterials in applications as diverse as gene therapy to biomanufacturing. We build whole-cell, physically- and biochemically-resolved models of bacteria to understand how physics at the colloidal scale instantiate life in biological cells and how corresponding processes can be engineered for new tools, drugs, diagnostics, and more. While principles from physics have driven recent paradigm shifts in understanding how collective biomolecular behaviors orchestrate life, many mechanistic aspects of key biological processes such as adaptation to environmental conditions remain murky because understanding and controlling them requires unifying two disparate physical regimes: the atomistic (structural biology) and the microscopic (systems biology). Colloidal-scale modeling bridges this divide, linking molecular-scale phenomena to whole-cell function. I will discuss our physically- and biochemically resolved whole-cell computational models of two bacterial cells, Escherichia coli and JCVI-Syn3A, a synthetic Mycoplasma with the minimal genome capable of life. I will discuss how we use these models to shed light on gains in function that lead matter to life and identify physics-based mechanisms ideal for microbe engineering.