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Biological Physics (iPoLS) Seminar: Zan Luthey-Schulten (UIUC) "Integrating experiments, theory and simulations into whole-cell models"

Event Type
Department of Physics
Beckman Institute 5602
Sep 23, 2022   2:00 pm  
Zan Luthey-Schulten
Brandy Koebbe
Originating Calendar
Physics - Biological Physics (iPoLS) Seminar

We present a whole-cell kinetic model (4DWCM) of JCVI-syn3A, a minimal bacterial cell with a reduced genome of 493 genes that has retained few regulatory proteins or small RNAs. Cryo-electron tomograms provide the cell geometry and ribosome distributions. Time-dependent behaviors of concentrations and reaction fluxes from stochastic-deterministic simulations over a cell cycle reveal how the cell balances demands of its metabolism, genetic information processes, and growth, and offer insight into the principles of life for this minimal cell. The energy economy of each process including active transport of amino acids, nucleosides, and ions is analyzed. The WCM reveals how emergent imbalances lead to slowdowns in the rates of transcription and translation. Integration of experimental data is critical in building a kinetic model from which emerges a genome-wide distribution of mRNA half-lives, multiple DNA replication events that can be compared to qPCR results, and the experimentally observed doubling behavior. Status of constructing a 4DWCM for the minimal eukaryotic cell, yeast, is briefly described. 

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