Bionanoscience (BN) seminar by prof.dr. Zaida Luthey-Schulten (University of Illinois, USA) on "Simulating a Cell Cycle in 3D for a Living Minimal Cell". The Luthey-Shulten group is a computational and theoretical biophysical chemistry group. Their current research is focused on: Modeling a minimal cell; Cell simulation software: lattice microbes; Energy metabolisms in cells; Combining metabolic and genetic information processes; Ribosome biogenesis in whole cells; Cell growth and division; Bistability in bacterial and yeast genetic switch; and, Whole cell model of HeLa cells. The talk will start at 12:45h, and lunch is provided from 12:30h.

Abstract:
To investigate the rules of cellular life, it is critical to understand the interactions that dictate cell fate and how they are spatially organized within a cell and affect cell morphology.  Having a near-minimal set of interactions while still accounting for the fundamental behavior of DNA replication and cell division, JCVI-syn3A, a genetically minimal bacterial cell, provides an ideal platform for constructing a dynamical 3D whole-cell model (4DWCM).  Here, we demonstrate the integration of spatial stochastic reaction-diffusion dynamics with well-stirred stochastic and deterministic chemical kinetics, a Brownian dynamics model of the chromosome, and a Hamiltonian Monte Carlo model of the cell membrane to simulate Syn3A cells over the course of minutes to hours of biological time.  These simulations also integrate a wide array of experimental data including -omics, cryo-electron tomograms, fluorescent imaging, and kinetic measurements to initialize a realistic cell state as well as validate the states as they progress in time.  The fluorescent imaging of the cell membrane and DNA distributions suggest symmetric cell division.  From the simulated time-dependent cell states, we quantify variations in cell cycle progress including the spatial distribution of ribosomes, growth and division progress, DNA replication states, and metabolic activity including a comprehensive accounting for all ATP costs.

Authors with affiliations: 
Zane R. Thornburg *1, Benjamin R. Gilbert *1, Troy A. Brier *1, Jiwoong Kwon *2, Jay E. Cournoyer *1, Angad P. Mehta *1, Taekjip Ha *2, John I. Glass *3, Zaida Luthey-Schulten *1, *4
1: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801
2: School of Medicine, Johns Hopkins University, Baltimore, MD 21205
3: Synthetic Biology Group, J. Craig Venter Institute, La Jolla, CA 92037
4. Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL 61801