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Early Metabolic Injury (LiSyM-EMI - Pillar I)

Overview

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. LiSyM-EMI looks into the transition from steatosis to non-alcoholic steatohepatitis (NASH) as the disease-defining moment in NAFLD. A systems analysis of these early disease events will be performed to elucidate the molecular mechanisms that trigger disease establishment.

SEEK ID: https://seek.lisym.org/projects/3

Public web page: Not specified

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus

FAIRDOM PALs: Vincent Moser, Lutz Brusch, Annika Schneider, Mario Brosch, Josch Pauling

Project created: 21st Feb 2017

Related items

Ann-Kristin Becker

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

Institutions: University Medicine Greifswald - Institute of Bioinformatics

Mario Brosch pal

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

Institutions: Universitätsklinikum Dresden - Medizinische Klinik I, Bereich Gastroenterologie & Hepatologie

Lutz Brusch pal

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

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

https://orcid.org/0000-0003-0137-5106
Helen Desmond project_administratorasset_housekeeper

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

Institutions: LiSyM programme directorate

Adrian Friebel

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

Institutions: Universität Leipzig - Institute for Computer Science (Bioinformatics)

LiSyM Pillar I: Early Metabolic Injury
Early Metabolic Injury (LiSyM-EMI - Pillar I)
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Mouse expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
...

Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

Human expression dataset (Comparison of Gene Expression Patterns Between Mouse Models of Nonalcoholic Fatty Liver Disease and Liver Tissues From Patients.)
Early Metabolic Injury (LiSyM-EMI - Pillar I)

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Mouse models of NAFLD have been used in studies of pathogenesis and treatment, and have certain features of the human disease. We performed a systematic transcriptome-wide analysis of liver tissues from patients at different stages of NAFLD progression (ranging from healthy obese individuals to those with steatosis), as well as rodent models of NAFLD, to identify
...

Creators: Mario Brosch, Jochen Hampe, Clemens Schafmayer, Witigo Von Schönfels

Contributor: Mario Brosch

PALs Meeting Hünfeld 2017 Agenda
LiSyM Core Infrastructure and Management (LiSyM-PD), Early Metabolic Injury (LiSyM-EMI - Pillar I), Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), Liver Function Diagnostics (LiSyM-LiFuDi - Pillar IV), 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)
No description specified

Creator: Martin Golebiewski

Contributor: Martin Golebiewski

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Morpheus: open source modelling and simulation framework for multicellular systems
Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM PALs

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://imc.zih.tu-dresden.de/wiki/morpheus
Open source code at: https://gitlab.com/morpheus.lab/morpheus

Creators: Lutz Brusch, Jörn Starruß, Walter de Back, Andreas Deutsch

Contributor: Lutz Brusch

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Morpheus model of spatio-temporal Smo regulation in response to Hh signaling
Early Metabolic Injury (LiSyM-EMI - Pillar I)

The model is adapted from A.P. Kupinski, I. Raabe, M. Michel, D. Ail, L. Brusch, T. Weidemann, C. Bökel (2013) Phosphorylation of the Smo tail is controlled by membrane localization and is dispensable for clustering, J. Cell Sci., 126, 20, 4684-4697 doi: 10.1242/​jcs.128926

The model format is MorpheusML that can readily be loaded and run in Morpheus: https://imc.zih.tu-dresden.de//wiki/morpheus

Creator: Lutz Brusch

Contributor: Lutz Brusch

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Spatio-temporal dynamics of Rab5 domains on the membrane of early endosomes
Early Metabolic Injury (LiSyM-EMI - Pillar I)

This model describes a core process during endocytosis. Intracellular vesicles called early endosomes contain the endocytosed cargo, e.g. signaling components like growth factors and RTKs, pathogens like viruses and nutrients like iron in transferrin. Early endosomes form an interacting pool of thousands of vesicles and jointly constitute the sorting and transport machinery in the endocytic pathway. Together with the cargo, membrane components travel to other compartments of the pathway which
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Creator: Lutz Brusch

Contributor: Lutz Brusch

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Electrosurgical liver resection has a superior regeneration outcome as compared to en-bloc ligation in a novel model of partial hepatectomy in mice
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Background: The extent of resection and the frequency of liver surgery have increased over the past decades, enabled by improved haemostasis provided by electrosurgical liver dissection. Because extensive … liver surgery is still associated with lethal complications, further optimisation of the technique and a better molecular understanding of hepatic wound healing and regeneration are needed. Systematic studies and a mouse model reflecting the clinical reality of liver surgery are lacking. Methods: We performed liver resection in mice with a monopolar electrocautery device in comparison to the classical en-bloc ligation method. Regeneration was assessed using liver weight and BrDU immunohistochemistry after sacrifice and non-invasively using micro computed tomography (µCT). Results: Mortality in the electrosurgical model was similar to the ligation method given an identical extent of resection. Regeneration of liver proceeded significantly faster in the electrosurgical group: Liver weight was 25.6% higher at sacrifice after 168h (p=0.0003). Concordantly, both µCT analysis (22.6% higher liver volume at 168h, p=0.008) and BrDU staining (71.4% higher proliferation at 72h, p=0.0005) indicated superior regeneration of liver after electrosurgical partial hepatectomy. Conclusions: The mode of liver resection has a profound impact on regeneration and should be studied molecularly using the presented novel model of electrosurgical liver resection.

Authors: W. von Schonfels, Clemens Schafmayer, Jochen Hampe

Date Published: No date defined

Journal: prepublication

Correlative SMLM and electron tomography reveals endosome nanoscale domains.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Many cellular organelles, including endosomes, show compartmentalization into distinct functional domains, which however cannot be resolved by diffraction-limited light microscopy. Single molecule … localization microscopy (SMLM) offers nanoscale resolution but data interpretation is often inconclusive when the ultrastructural context is missing. Correlative light electron microscopy (CLEM) combining SMLM with electron microscopy (EM) enables correlation of functional sub-domains of organelles in relation to their underlying ultrastructure at nanometer resolution. However, the specific demands for EM sample preparation and the requirements for fluorescent single-molecule photo-switching are opposed. Here, we developed a novel superCLEM workflow that combines triple-colour SMLM (dSTORM & PALM) and electron tomography using semi-thin Tokuyasu thawed cryosections. We applied the superCLEM approach to directly visualize nanoscale compartmentalization of endosomes in HeLa cells. Internalized, fluorescently labelled Transferrin and EGF were resolved into morphologically distinct domains within the same endosome. We found that the small GTPase Rab5 is organized in nano-domains on the globular part of early endosomes. The simultaneous visualization of several proteins in functionally distinct endosomal sub-compartments demonstrates the potential of superCLEM to link the ultrastructure of organelles with their molecular organization at nanoscale resolution. This article is protected by copyright. All rights reserved.

Authors: C. Franke, U. Repnik, S. Segeletz, N. Brouilly, Y. Kalaidzidis, J. M. Verbavatz, Marino Zerial

Date Published: 17th Jun 2019

Journal: Traffic

Liquid-crystal organization of liver tissue.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

Functional tissue architecture originates by self-assembly of distinct cell types, following tissue-specific rules of cell-cell interactions. In the liver, a structural model of the lobule was pioneered … by Elias in 1949. This model, however, is in contrast with the apparent random 3D arrangement of hepatocytes. Since then, no significant progress has been made to derive the organizing principles of liver tissue. To solve this outstanding problem, we computationally reconstructed 3D tissue geometry from microscopy images of mouse liver tissue and analyzed it applying soft-condensed-matter-physics concepts. Surprisingly, analysis of the spatial organization of cell polarity revealed that hepatocytes are not randomly oriented but follow a long-range liquid-crystal order. This does not depend exclusively on hepatocytes receiving instructive signals by endothelial cells, since silencing Integrin-beta1 disrupted both liquid-crystal order and organization of the sinusoidal network. Our results suggest that bi-directional communication between hepatocytes and sinusoids underlies the self-organization of liver tissue.

Authors: H. Morales-Navarrete, H. Nonaka, A. Scholich, F. Segovia-Miranda, W. de Back, K. Meyer, R. L. Bogorad, V. Koteliansky, Lutz Brusch, Y. Kalaidzidis, F. Julicher, B. M. Friedrich, Marino Zerial

Date Published: 17th Jun 2019

Journal: Elife

Wet-tip versus dry-tip regimes of osmotically driven fluid flow
Early Metabolic Injury (LiSyM-EMI - Pillar I)

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

Journal: Sci Rep

Evolutionary Distance Predicts Recurrence After Liver Transplantation in Multifocal Hepatocellular Carcinoma.
Early Metabolic Injury (LiSyM-EMI - Pillar I)

Abstract (Expand)

BACKGROUND: Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may … be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. METHODS: In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. RESULTS: Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 x 10) and microvascular invasion (P = 1.31 x 10) were significantly associated with survival in a Cox regression analysis. CONCLUSIONS: Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered.

Authors: N. Heits, Mario Brosch, A. Herrmann, R. Behrens, C. Rocken, H. Schrem, A. Kaltenborn, J. Klempnauer, H. H. Kreipe, B. Reichert, C. Lenschow, C. Wilms, T. Vogel, H. Wolters, E. Wardelmann, D. Seehofer, S. Buch, S. Zeissig, S. Pannach, N. Raschzok, M. Dietel, W. von Schoenfels, S. Hinz, A. Teufel, M. Evert, A. Franke, Ann-Kristin Becker, F. Braun, Jochen Hampe, Clemens Schafmayer

Date Published: 12th Jul 2018

Journal: Transplantation

Poster 8 LiSyM-Midterm_Evaluation_Hampe
Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM network
No description specified

Creators: Mario Brosch, Jochen Hampe

Contributor: Mario Brosch

LiSyM Midterm Evaluation Poster 7 - Schwab/Hofmann
Early Metabolic Injury (LiSyM-EMI - Pillar I)
No description specified

Creators: Ute Hofmann, Matthias Schwab

Contributor: Ute Hofmann

LiSyM Midterm Evaluation 2018 poster 9 Shevchenko group
Early Metabolic Injury (LiSyM-EMI - Pillar I), LiSyM network

Shotgun lipidomics of microdissected periportal and pericentral zones; Characterization of NAFLD in Human Liver Biopsies by Shotgun Lipidomics

Creators: Oskar Knittelfelder, Olga Vvedenskaya

Contributor: Oskar Knittelfelder

Poster midterm evaluation Pillar I, WP6
Early Metabolic Injury (LiSyM-EMI - Pillar I)
No description specified

Creator: Witigo Von Schönfels

Contributor: Witigo Von Schönfels

Presentation LiSyM Data Management - 1st LiSyM Jamboree & SAB Meeting, Dresden, May 16-17, 2017 Wolfgang Müller and Martin Golebiewski
LiSyM Core Infrastructure and Management (LiSyM-PD), Early Metabolic Injury (LiSyM-EMI - Pillar I), Chronic Liver Disease Progression (LiSyM-DP - Pillar II), Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), Liver Function Diagnostics (LiSyM-LiFuDi - Pillar IV), 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
No description specified

Creator: Martin Golebiewski

Contributor: Martin Golebiewski

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First LiSyM PostDoc and PhD student retreat

The meeting will provide a great opportunity for discussion between modellers, experimentalists and clinicians and to organize and harmonize our future work within the LiSyM network on the grassroot level.

Start Date: 20th Nov 2017

End Date: 22nd Nov 2017

Event Website: Not specified

Country:  Germany

City: Hünfeld

International Conference on Systems Biology of Human Disease (SBHD)

The International Conference on Systems Biology of Human Disease (SBHD) is a transatlantic event and communication platform for scientific exchange that takes place alternately between the United States and Germany.

SBHD 2017 is continuing a conference series launched by Peter Sorger and colleagues from Harvard Medical School in 2008. The conference focus is on mammalian systems biology, particularly on its application to human disease and therapy.

Start Date: 5th Jul 2017

End Date: 7th Jul 2017

Event Website: http://www.sbhd-conference.org/2017/index.php

Country:  Germany

City: Heidelberg

First EASL Nonalcoholic Fatty Liver Disease (NAFLD) Summit: Target-oriented approach to Diagnosis and Pharmacotherapy of Nonalcoholic Steatohepatitis (NASH), a dialogue between Academia and Industry

This summit will cover both the basic and translational / clinical aspects of NAFLD, with a specific focus on novel drug target and prognostic signature development.

Key sessions include all crucial pathophysiological aspects currently known to affect development and progression of NAFLD, such as "lipid metabolism and lipotoxicity" and "insulin resistance, insulin and hormonal signaling". Furthermore, oxidative stress, ER stress, and mitochondrial dysfunction will be addressed. On the second day,
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Start Date: 9th Nov 2017

End Date: 11th Nov 2017

Event Website: https://events.easl.eu/EventPortal/Information/EventInformation.aspx?EventInformationPageCode=HOME&EventCode=nafld2017

Country:  Italy

City: Rome

18th International Conference on Systems Biology (ICSB 2017)

ICSB continues to be the flagship conference of the International Society for Systems Biology (ISSB). The conference will cover a variety of themes from Fundamental Biological Sciences, Network Analysis, to Metabolic Engineering and Cancer Biology. The conference will also include a variety of engaging plenary lectures, parallel sessions, poster sessions, and interactive networking opportunities.

Abstract submission deadline: May 13th, 2017

Start Date: 6th Aug 2017

End Date: 12th Aug 2017

Event Website: http://www.cpe.vt.edu/icsb2017/

Country:  United States

City: Blacksburg, Virginia

Joint LiSyM & ERASysAPP Data Management PALs Meeting

This event is a jointly organized Data Management PALs Meeting that involves PALs from the German LiSyM (Liver Systems Medicine) network and from the ERASysAPP (ERA-Net for Systems Biology Applications) initiative. PALs (Project Area Liaisons) are the front line experts of the data management teams of these projects. They act as data management advocates and help gathering user requirements and testing potential data management solutions. An important part of the meeting will be to gather the
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Start Date: 2nd May 2017

End Date: 3rd May 2017

Event Website: https://fairdomhub.org/events/64

Country:  Germany

City: 36088 Hünfeld bei Fulda

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