2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016

From pieces to the whole — Concepts for modular modelling of yeast

Jens Hahn1, Stefan Forgo1, Jorin Diemer1, Katja Tummler1, Tom Altenburg1, Stephan O. Adler1, Judith Wodke1, Max Schelker1, Thomas W. Spiesser1, Ulrike Münzner1, Friedemann Uschner1, Sebastian Thieme1, Ana Bulović1, Paula Martinell1, Marcus Krantz1, Martin Seeger1, Max Flöttmann1, Jannis Uhlendorf1, Edda Klipp1

1 - Humboldt-Universität zu Berlin,Germany

Keywords: Saccharomyces cerevisiae, Modelling, ODE


A large number of detailed high quality models of specific cellular processes have over the last years proven to be valuable for the understanding of biological functionality. However, they disregard interactions with other intracellular processes and the embedding in higher order processes, such as cell cycle, volume variation, and environmental conditions. The integration of those functionalities of different levels of cell granularity and time-scales is itself technically challenging.

We present a first approach to solve these issues by combining a model of yeast cell cycle and gene regulation in the context of a changing cell size and minimal metabolism. The cell cycle model includes the key cyclins and their kinases, whose expression is controlled by the gene expression model. These models are embedded in a biophysical description of the cell physiology and coupled to a coarse-grained carbon metabolism to include sensitivity to nutrient availability.

To combine and simulate the different modules, we developed a software environment that specifically tackles the challenges of integrating biological models with conceptually different mathematical formulations, time-scales, and resolutions. The framework is written in Python and provides several numerical solvers, SBML support and a COPASI interface.

Our approach focuses on the interfaces between biological processes represented in different modules. The modules themselves can be modified independently and easily exchanged within the framework. We provide a comprehensive and reproducible method to define and characterise interfaces between different modules and use these interfaces to simulate models together, even if they rely on different modelling approaches.

Conference Program