Bringing Cells to Life of the Computer: Whole-Cell Modeling from Minimal Bacteria to Human Cells
April 16, 2025 @ 10:30 – 11:30 CEST
Speaker
Zane R Thornburg, PhD
Chemical Imaging and Structures Laboratory
University of Illinois Urbana-Champaign
Abstract
The goal of whole-cell modeling is to computationally predict the temporal progression of cell states. To simulate minutes to hours of biological time, we sacrifice atomic resolution and instead use coarse-grained hybrid simulations. In these models, large structures like membranes are projected onto a 3D cubic lattice, macromolecules like proteins are individual particles, and small molecules like metabolites are tracked as dynamic concentrations. Our most complete model is the genetically minimal bacterium in which we successfully simulate an entire cell cycle from start to division in 3D including the entire metabolic network and expression of its 493 genes. Organisms of more practical interest are significantly more complicated, and many challenges still need to be discovered and overcome to model them. I will present two ongoing efforts in the areas of cell metabolism and mRNA splicing. One of the greatest challenges in metabolic modelling is determining a set of kinetic parameters. We present a method to determine sets of thermodynamically realistic kinetic parameters for enzymatic reactions in whole-cell metabolic models. The fate of a eukaryotic cell depends on proper maturation of its pre-mRNA through splicing. Variations in splicing of pre-mRNA from a single gene (alternative splicing) result in multiple isoforms of mature mRNA, each producing a different protein with distinct biological activities. We model the kinetics of splicing to predict the frequencies at which the isoforms occur and demonstrate the model’s capabilities and limitations using known splicing isoforms from the human genome.
Contact: Erik Lindahl (erik.lindahl@scilifelab.se)
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