Morpheus: open source modelling and simulation framework for multicellular systems
Version 1

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Morpheus is the modelling and simulation framework for multicellular systems biology developed at Technische Universität Dresden. Manual, examples and binaries for Windows, Linux, MacOS at: https://morpheus.gitlab.io Open source code at: https://gitlab.com/morpheus.lab/morpheus

SEEK ID: https://seek.lisym.org/models/4?version=1

2 items (and an image) are associated with this Model:

Morpheus.pdf (PDF document - 215 KB)
Morpheus_Supplement.pdf (PDF document - 2.49 MB)

Organism: Not specified

Model type: Agent based modelling

Model format: MorpheusML

Execution or visualisation environment: Morpheus

Model image: (Click on the image to zoom) (Original)

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Creators and Submitter

Creator

Lutz Brusch

Additional credit

Jörn Starruß, Walter de Back, Andreas Deutsch

Submitter

Lutz Brusch

License

Creative Commons Attribution 4.0

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Views: 3676 Downloads: 952

Created: 21st Jul 2017 at 17:13

Last updated: 26th Feb 2020 at 20:34

Version History

Version 1 (earliest) Created 21st Jul 2017 at 17:13 by Lutz Brusch

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People (1)
Programmes (1)
Projects (2)
Publications (6)

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Lutz Brusch

Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM PALs, LiSyM network, LiSyM-Krebs Partnering, Forschungsnetzwerk LiSyM-Krebs, DEEP-HCC network

Institutions: Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Technische Universität Dresden

https://orcid.org/0000-0003-0137-5106

Expertise: computational biology, computational modelling, kinetic modelling, Mathematical Modelling, Standards, Biophysics, Signal transduction, Spatio-temporal Modelling

Tools: Copasi, Cytoscape, SBML, SED-ML, Morpheus, Stability analysis, Bifurcation analysis, Multiscale simulation

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

Web page: https://www.lisym.org/

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LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research/zones-of-the-liver

Start date: 1st Jan 2016

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus, Homo sapiens

LiSyM PALs

This is a generic project that comprises all LiSyM data management PALs and associated FAIRDOM PALs, as well as the LiSyM data management team. Olga Maja Alain

Programme: LiSyM: Liver Systems Medicine

Public web page: Not specified

Organisms: Not specified

Showing 5 out of a possible 6 Publications Advanced Publications list for this Model with search and filtering

Bile canaliculi remodeling activates YAP via the actin cytoskeleton during liver regeneration

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

All authors

Lutz Brusch

Marino Zerial

Abstract (Expand)

The mechanisms of organ size control remain poorly understood. A key question is how cells collectively sense the overall status of a tissue. We addressed this problem focusing on mouse liver regeneration. … Using digital tissue reconstruction and quantitative image analysis, we found that the apical surface of hepatocytes forming the bile canalicular network expands concomitant with an increase in F‐actin and phospho‐myosin, to compensate an overload of bile acids. These changes are sensed by the Hippo transcriptional co‐activator YAP, which localizes to apical F‐actin‐rich regions and translocates to the nucleus in dependence of the integrity of the actin cytoskeleton. This mechanism tolerates moderate bile acid fluctuations under tissue homeostasis, but activates YAP in response to sustained bile acid overload. Using an integrated biophysical–biochemical model of bile pressure and Hippo signaling, we explained this behavior by the existence of a mechano‐sensory mechanism that activates YAP in a switch‐like manner. We propose that the apical surface of hepatocytes acts as a self‐regulatory mechano‐sensory system that responds to critical levels of bile acids as readout of tissue status.

Authors: Kirstin Meyer, Hernan Morales‐Navarrete, Sarah Seifert, Michaela Wilsch‐Braeuninger, Uta Dahmen, Elly M Tanaka, Lutz Brusch, Yannis Kalaidzidis, Marino Zerial

Date Published: 24th Feb 2020

Publication Type: Not specified

DOI: 10.15252/msb.20198985

Citation: Mol Syst Biol 16(2) : 186

Created: 26th Feb 2020 at 19:44, Last updated: 8th Mar 2024 at 07:44

An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

All creators

Lutz Brusch

Abstract (Expand)

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research … product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research.

Authors: Hartwig Anzt, Felix Bach, Stephan Druskat, Frank Löffler, Axel Loewe, Bernhard Y. Renard, Gunnar Seemann, Alexander Struck, Elke Achhammer, Piush Aggarwal, Franziska Appel, Michael Bader, Lutz Brusch, Christian Busse, Gerasimos Chourdakis, Piotr Wojciech Dabrowski, Peter Ebert, Bernd Flemisch, Sven Friedl, Bernadette Fritzsch, Maximilian D. Funk, Volker Gast, Florian Goth, Jean-Noël Grad, Sibylle Hermann, Florian Hohmann, Stephan Janosch, Dominik Kutra, Jan Linxweiler, Thilo Muth, Wolfgang Peters-Kottig, Fabian Rack, Fabian H.C. Raters, Stephan Rave, Guido Reina, Malte Reißig, Timo Ropinski, Joerg Schaarschmidt, Heidi Seibold, Jan P. Thiele, Benjamin Uekermann, Stefan Unger, Rudolf Weeber

Date Published: 2020

Publication Type: Not specified

DOI: 10.12688/f1000research.23224.1

Citation: F1000Res 9 : 295

Created: 29th Jun 2020 at 07:42, Last updated: 8th Mar 2024 at 07:44

Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression.

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM network

(Show All)

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Fabian Segovia Miranda

Michael Kücken

Vincent Moser

Fabian Rost

Mario Brosch

Clemens Schafmayer

Lutz Brusch

Jochen Hampe

Marino Zerial

Abstract (Expand)

Early disease diagnosis is key to the effective treatment of diseases. Histopathological analysis of human biopsies is the gold standard to diagnose tissue alterations. However, this approach has low … resolution and overlooks 3D (three-dimensional) structural changes resulting from functional alterations. Here, we applied multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD). We identified a set of morphometric cellular and tissue parameters correlated with disease progression, and discover profound topological defects in the 3D bile canalicular (BC) network. Personalized biliary fluid dynamic simulations predicted an increased pericentral biliary pressure and micro-cholestasis, consistent with elevated cholestatic biomarkers in patients' sera. Our spatially resolved models of human liver tissue can contribute to high-definition medicine by identifying quantitative multiparametric cellular and tissue signatures to define disease progression and provide new insights into NAFLD pathophysiology.

Authors: F. Segovia-Miranda, H. Morales-Navarrete, M. Kucken, V. Moser, S. Seifert, U. Repnik, F. Rost, M. Brosch, A. Hendricks, S. Hinz, C. Rocken, D. Lutjohann, Y. Kalaidzidis, C. Schafmayer, L. Brusch, J. Hampe, M. Zerial

Date Published: 2nd Dec 2019

Publication Type: Not specified

PubMed ID: 31792455

Citation: Nat Med. 2019 Dec 2. pii: 10.1038/s41591-019-0660-7. doi: 10.1038/s41591-019-0660-7.

Created: 4th Dec 2019 at 10:11, Last updated: 8th Mar 2024 at 07:44

Wet-tip versus dry-tip regimes of osmotically driven fluid flow

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

All authors

Jochen Hampe

Lutz Brusch

Abstract (Expand)

The secretion of osmolytes into a lumen and thereby caused osmotic water inflow can drive fluid flows in organs without a mechanical pump. Such fluids include saliva, sweat, pancreatic juice and bile. … The effects of elevated fluid pressure and the associated mechanical limitations of organ function remain largely unknown since fluid pressure is difficult to measure inside tiny secretory channels in vivo. We consider the pressure profile of the coupled osmolyte-flow problem in a secretory channel with a closed tip and an open outlet. Importantly, the entire lateral boundary acts as a dynamic fluid source, the strength of which self-organizes through feedback from the emergent pressure solution itself. We derive analytical solutions and compare them to numerical simulations of the problem in three-dimensional space. The theoretical results reveal a phase boundary in a four-dimensional parameter space separating the commonly considered regime with steady flow all along the channel, here termed “wet-tip” regime, from a “dry-tip” regime suffering ceased flow downstream from the closed tip. We propose a relation between the predicted phase boundary and the onset of cholestasis, a pathological liver condition with reduced bile outflow. The phase boundary also sets an intrinsic length scale for the channel which could act as a length sensor during organ growth.

Authors: Oleksandr Ostrenko, Jochen Hampe, Lutz Brusch

Date Published: 1st Dec 2019

Publication Type: Not specified

DOI: 10.1038/s41598-019-40853-7

Citation: Sci Rep 9(1) : 823

Created: 20th May 2019 at 15:27, Last updated: 8th Mar 2024 at 07:44

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)

(Show All)

All authors

Erik Kolbe

Christiane Körner

Fritzi Ott

David Meierhofer

Stefan Hoehme

Michael Kücken

Lutz Brusch

Witigo von Schönfels

Clemens Schafmayer

Mario Brosch

Ute Hofmann

Jochen Hampe

Madlen Matz-Soja

Georg Damm

Daniel Seehofer

Abstract (Expand)

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and … control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well.

Authors: Erik Kolbe, Susanne Aleithe, Christiane Rennert, Luise Spormann, Fritzi Ott, David Meierhofer, Robert Gajowski, Claus Stöpel, Stefan Hoehme, Michael Kücken, Lutz Brusch, Michael Seifert, Witigo von Schoenfels, Clemens Schafmayer, Mario Brosch, Ute Hofmann, Georg Damm, Daniel Seehofer, Jochen Hampe, Rolf Gebhardt, Madlen Matz-Soja

Date Published: 1st Dec 2019

Publication Type: Not specified

DOI: 10.1016/j.celrep.2019.11.104

Citation: Cell Reports 29(13) : 4553

Created: 22nd Jan 2020 at 09:56, Last updated: 8th Mar 2024 at 07:44

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Morpheus: open source modelling and simulation framework for multicellular systems Version 1

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Version History

Version 1 (earliest) Created 21st Jul 2017 at 17:13 by Lutz Brusch

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Morpheus: open source modelling and simulation framework for multicellular systems
Version 1