Stochastic and Nonlinear Biological Dynamics
In physics we can make remarkable progress with very simple models. In biology we cannot. Non-linearity is all pervasive as living systems are in constant exchange with their environments and complex feedback structures govern processes from the molecular to the ecosystem level. We have been investigating how such feedbacks shape cellular and tissue-level processes, and how we can learn to control and guide non-linear systems.
Much of our work focusses on the interplay between non-linear dynamics and stochasticity. This is an incredible fruitful and exciting area of research, both mathematically and biologically. Mathematically we have to combine traditional paper-and-pencil calculations with state-of-the-art computer simulations. The precise manner in which noise and non-linearity interact can shape the organisation of biological systems profoundly, and we combine our mathematical work with data analysis and work closely with experimental and clinical collaborators to understand the drivers of life at the cellular scale.
Whether bifurcations persist once dynamics are stochastic, for example, is a surprisingly subtle problem but one of great biological importance in cell biology.

Team
Adriana Zanca
Cell Fates, Cell States, and Cell MapsNetworks, Trees, and Landscapes
Latest research
2018
Tomasz Jetka; Karol Nienałtowski; Sarah Filippi; Michael P.H. Stumpf; Michał Komorowski
An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling Journal Article
In: Nat Commun, vol. 9, no. 1, 2018, ISSN: 2041-1723.
Abstract | Links | BibTeX | Tags: Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics
@article{Jetka2018,
title = {An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling},
author = {Tomasz Jetka and Karol Nienałtowski and Sarah Filippi and Michael P.H. Stumpf and Michał Komorowski},
doi = {10.1038/s41467-018-07085-1},
issn = {2041-1723},
year = {2018},
date = {2018-12-00},
urldate = {2018-12-00},
journal = {Nat Commun},
volume = {9},
number = {1},
publisher = {Springer Science and Business Media LLC},
abstract = {<jats:title>Abstract</jats:title><jats:p>Many components of signaling pathways are functionally pleiotropic, and signaling responses are marked with substantial cell-to-cell heterogeneity. Therefore, biochemical descriptions of signaling require quantitative support to explain how complex stimuli (inputs) are encoded in distinct activities of pathways effectors (outputs). A unique perspective of information theory cannot be fully utilized due to lack of modeling tools that account for the complexity of biochemical signaling, specifically for multiple inputs and outputs. Here, we develop a modeling framework of information theory that allows for efficient analysis of models with multiple inputs and outputs; accounts for temporal dynamics of signaling; enables analysis of how signals flow through shared network components; and is not restricted by limited variability of responses. The framework allows us to explain how identity and quantity of type I and type III interferon variants could be recognized by cells despite activating the same signaling effectors.</jats:p>},
keywords = {Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics},
pubstate = {published},
tppubtype = {article}
}
2017
Adam L. MacLean; Maia A. Smith; Juliane Liepe; Aaron Sim; Reema Khorshed; Narges M. Rashidi; Nico Scherf; Axel Krinner; Ingo Roeder; Cristina Lo Celso; Michael P.H. Stumpf
Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection Journal Article
In: vol. 35, no. 11, pp. 2292–2304, 2017, ISSN: 1549-4918.
Abstract | Links | BibTeX | Tags: Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics
@article{MacLean2017,
title = {Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection},
author = {Adam L. MacLean and Maia A. Smith and Juliane Liepe and Aaron Sim and Reema Khorshed and Narges M. Rashidi and Nico Scherf and Axel Krinner and Ingo Roeder and Cristina Lo Celso and Michael P.H. Stumpf},
doi = {10.1002/stem.2692},
issn = {1549-4918},
year = {2017},
date = {2017-11-01},
urldate = {2017-11-01},
volume = {35},
number = {11},
pages = {2292--2304},
publisher = {Oxford University Press (OUP)},
abstract = {<jats:title>Abstract</jats:title>
<jats:p>The hematopoietic stem cell (HSC) niche provides essential microenvironmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, hematopoietic dynamics are perturbed, but it is not known whether changes to the HSC–niche interaction occur as a result. We visualize HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behavior: (a) a pattern of revisiting previously explored space and (b) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (a), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life-history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC–niche microenvironments following infection.</jats:p>},
keywords = {Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics},
pubstate = {published},
tppubtype = {article}
}
<jats:p>The hematopoietic stem cell (HSC) niche provides essential microenvironmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, hematopoietic dynamics are perturbed, but it is not known whether changes to the HSC–niche interaction occur as a result. We visualize HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow following Trichinella spiralis infection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behavior: (a) a pattern of revisiting previously explored space and (b) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (a), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life-history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC–niche microenvironments following infection.</jats:p>
2016
Helen Weavers; Juliane Liepe; Aaron Sim; Will Wood; Paul Martin; Michael P.H. Stumpf
Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient Journal Article
In: Current Biology, vol. 26, no. 15, pp. 1975–1989, 2016, ISSN: 0960-9822.
Links | BibTeX | Tags: Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics
@article{Weavers2016,
title = {Systems Analysis of the Dynamic Inflammatory Response to Tissue Damage Reveals Spatiotemporal Properties of the Wound Attractant Gradient},
author = {Helen Weavers and Juliane Liepe and Aaron Sim and Will Wood and Paul Martin and Michael P.H. Stumpf},
doi = {10.1016/j.cub.2016.06.012},
issn = {0960-9822},
year = {2016},
date = {2016-08-00},
urldate = {2016-08-00},
journal = {Current Biology},
volume = {26},
number = {15},
pages = {1975--1989},
publisher = {Elsevier BV},
keywords = {Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics},
pubstate = {published},
tppubtype = {article}
}
Sarah Filippi; Chris P. Barnes; Paul D.W. Kirk; Takamasa Kudo; Katsuyuki Kunida; Siobhan S. McMahon; Takaho Tsuchiya; Takumi Wada; Shinya Kuroda; Michael P.H. Stumpf
Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling Journal Article
In: Cell Reports, vol. 15, no. 11, pp. 2524–2535, 2016, ISSN: 2211-1247.
Links | BibTeX | Tags: Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics
@article{Filippi2016,
title = {Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling},
author = {Sarah Filippi and Chris P. Barnes and Paul D.W. Kirk and Takamasa Kudo and Katsuyuki Kunida and Siobhan S. McMahon and Takaho Tsuchiya and Takumi Wada and Shinya Kuroda and Michael P.H. Stumpf},
doi = {10.1016/j.celrep.2016.05.024},
issn = {2211-1247},
year = {2016},
date = {2016-06-00},
urldate = {2016-06-00},
journal = {Cell Reports},
volume = {15},
number = {11},
pages = {2524--2535},
publisher = {Elsevier BV},
keywords = {Fate cells | Cell states and Cell maps, Stochastic and nonlinear biological dynamics},
pubstate = {published},
tppubtype = {article}
}