Preprint Publication - Spatial Heterogeneity Alters the Dynamics of the Yeast Galactose Switch: Insights from 4D RDME–ODE Hybrid Simulations

Created on July 23, 2025

2025

Preprint Publication 🔬
📅 July 23, 2025
📄 bioRxiv
�� DOI: https://doi.org/10.1101/2025.07.23.666409
👥 Tianyu Wu, Marie-Christin Spindler, Emmy Earnest, Henry Li, Zane R. Thornburg, Julia Mahamid, Zaida Luthey-Schulten

We are excited to announce the publication of our preprint on “Spatial Heterogeneity Alters the Dynamics of the Yeast Galactose Switch: Insights from 4D RDME–ODE Hybrid Simulations” on bioRxiv. This work represents a significant advancement in whole-cell modeling of eukaryotic systems.

Key Innovations:

  • First 4D simulations of the galactose switch in Saccharomyces cerevisiae
  • Hybrid framework integrating reaction-diffusion master equations (RDMEs) with ordinary differential equations (ODEs)
  • GPU-based Lattice Microbes platform enabling realistic whole-cell simulations
  • Cryo-electron tomogram (cryo-ET) derived cell geometry for unprecedented spatial accuracy

Major Findings:

  • 11 mM extracellular galactose triggers expression of 10,000-15,000 galactose transporters within 60 minutes
  • Spatial differentiation between cytosolic and ER-associated ribosomes enables realistic protein translation modeling
  • Multi-GPU performance benchmarking across various spatial decompositions
  • Cellular geography significantly impacts genetic information processing and protein production

Technical Highlights:

  • Stochastic simulation of genetic information processes
  • Deterministic modeling of simplified metabolism
  • Explicit tracking of membrane-targeted proteins like galactose transporter Gal2
  • Quantification of ER maze-like structure effects on protein delivery

This work demonstrates the feasibility of whole-cell modeling in eukaryotic systems and reveals how spatial heterogeneity fundamentally alters cellular decision-making processes. Our framework paves the way for more complex organism simulations and provides insights into the critical role of cellular architecture in genetic regulation.

🔬 Read the full preprint on bioRxiv