C-TIP-HCC- Mechanism-based Multiscale Model to Dissect the Tipping Point from Liver Cirrhosis to Hepatocellular Carcinoma

The ultimate goal of the C-TIP-HCC is a „mechanistic multiscale model to describe dynamic changes in regenerative nodes across a tipping point (TIP) towards development in patients with cirrhosis to facilitate early monitoring and intervention“ and facilitate intervention“. To achieve this, we will conduct in-depth studies on cirrhotic regenerative nodes.

DEEP-HCC - Detailed Analysis of the Spatial Organization of the Development of Hepatocellular Carcinoma

SMART-NAFLD : A Systems Medicine Approach to Early Detection and Prevention of Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease

The massive increase in obesity is leading to an alarming rise in non-alcoholic liver disease (NAFLD). This development will lead to a dramatic increase in liver diseases such as hepatocellular carcinoma (HCC). A particular challenge is that NAFLD-associated HCCs, for reasons still unknown, not only occur in association with advanced liver fibrosis/cirrhosis, ...

Forschungsnetzwerk zur Früherkennung und Prävention- LiSyM-Krebs

Ein Netzwerk von Klinikern, Wissenschaftlern und Datenmanagern hat sich zur Aufgabe gemacht, Methoden zu entwickeln, um Patienten mit einem hohen Risiko für ein Leberkarzinom frühzeitig, in Vorstadien der Tumorentwicklung, identifizieren zu können. Gemeinsam bilden sie das „Systemmedizinische Forschungsnetzwerk zur Früherkennung und Prävention von Leberkrebs“, LiSym-Krebs, das vom Bundesministerium für Bildung und Forschung ...

This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

Due to increasing incidence and high mortality rates, hepatocellular carcinoma (HCC) is an important health problem worldwide. However, its etiopathology and development are poorly understood. While liver metabolism is organized in spatially specific zones, little is known how the zonation is associated with the onset and propagation of liver diseases. To this end, we applied laser capture microdissection (LCM) technique to excise histologically specific features of liver tissues, healthy and ...

Macrophages play an important role in maintaining liver homeostasis and regeneration. Here we investigate how different macrophage populations of the liver differ in terms of their activation state and which other liver cell populations may play a role in regulating the same.

LiSyM-Cancer project data for integration into public repositories based on

FAIR principles

Reverse transcription PCR, flow cytometry, transcriptome, proteome, secretome, single cell analysis, and immunohistochemical methods were used to study changes in gene expression as well as the activation state of macrophages in vitro and in vivo under homeostatic conditions and after partial hepatectomy.

Several proteomics experimental data

OTHER OMICS DATA

METABOLOMICS

GENOMICS/TRANSCRIPTOMICS

In this study, we characterize Western diet-induced phenotypic changes in murine 392 hepatocytes and employ dynamic pathway modelling to resolve the underlying molecular 393 mechanisms resulting in altered intracellular signal transduction and enhanced proliferation 394 of WD hepatocytes.

Documents submitted to BMBF

Documents submitted to BMBF

Project proposals

Meeting minutes 2021

Meeting minutes 2022

Project deliverables 2021

Project deliverables 2022

DMPlaning 2021

DMPlaning 2022

The liver comprises the body´s largest pool of macrophages constituting approximately 80 % of all sessile tissue macrophages of the body. After liver damage monocyte-derived macrophages are recruited into the liver and were here affected by a micro milieu which is considerably influenced by hepatocytes. Up to now the complex network that determines the differentiation and function of liver macrophages and the impact of the intercellular communication between macrophages and the other parenchymal ...

We describe a distinct macrophage population, whose presence in the liver during homoeostasis depends on recruitment signals mediated by the chemokine receptor CCR2. The identified polarization state of this population closely resembles that induced in co-culture experiments, where hepatocytes are reducing the availability of TGFb to macrophages. Accordingly, disruption of TGFb signal transduction in macrophages phenocopies the influence of hepatocytes on macrophage polarization.

Transcriptomics: the RNA expression of primary hepatocytes and BMDM (Bone Marrow–Derived acrophages) were analysed in 4 different conditions (mono- vs. co-culture, hepatocytes and macrophages) with 5 replicas each to detect the impact of hepatocytes on macrophages and vice versa.

Prof. Dr. Thomas Berg from University Medical Center Leipzig, Medical Department II – Oncology, Gastroenterology, Hepatology, Pneumology talked about "Bridging Basic Science and Clinical Practice: Background and Future Perspectives on Steatotic Liver Disease in the LiSyM Cancer Context". This seminar was the kick-off event of the LiSyM Cancer Seminar Series.

Hepatocyte-controlled availability of activated TGFb reprograms macrophage polarization affecting liver injury and regeneration

Raw data of proteomic analysis of primary murine hepatocytes treated with Hedgehog-modulating compounds

Manuscript: "Impact of Hedgehog Modulators on Signaling Pathways in Primary Murine and Human Hepatocytes in vitro: Insights into Liver Metabolism" Journal Name: Archives of Toxicology Author Names: Fritzi Ott, Christiane Körner, Knut Krohn, Janett Fischer, Georg Damm, Daniel Seehofer, Thomas Berg, Madlen Matz-Soja Corresponding author: Madlen Matz-Soja (madlen.matz-soja@medizin.uni-leipzig.de) ...

Raw data of RNA-seq analysis of primary murine hepatocytes treated with Hh modulating compounds

Manuscript: "Impact of Hedgehog Modulators on Signaling Pathways in Primary Murine and Human Hepatocytes in vitro: Insights into Liver Metabolism" Journal Name: Archives of Toxicology Author Names: Fritzi Ott, Christiane Körner, Knut Krohn, Janett Fischer, Georg Damm, Daniel Seehofer, Thomas Berg, Madlen Matz-Soja Corresponding author: Madlen Matz-Soja (madlen.matz-soja@medizin.uni-leipzig.de)

Supplementary Tables 1-7 of the Manuscript: "Multiomics and kinetic modeling reveal dominance of 12-hour rhythms in global liver metabolism"

for table headings please refer to Supplementary Material

Data deposited on the European Bioinformatics Insititute (EBI) database under accession number E-MTAB- 11727 (https://www.ebi.ac.uk/arrayexpress/experiments/ E-MTAB-11727)

Hepatocyte-controlled availability of activated TGFb reprograms macrophage polarization affecting liver injury and regeneration.

Samples in SEEK (ArrayExpress-compliant sample type https://seek.lisym.org/sample_types/21)

Hepatocytes and macrophages from mono and co-culture were harvested and prepared for mass spectrometric analysis , samples were shortly separated in a polyacrylamide gel, silver-stained, reduced, alkylated and digested with trypsin.

The model studies the influence of hepatocyte–sinusoid alignment (HSA), i.e. the orientation of the division plane such that daughter hepatocytes align with nearby sinusoids, on the shape of tumor nodules in liver lobules. It employs the structure of the model ‘Liver Regeneration from CCl4’ (https://seek.lisym.org/models/19).

Originally, Höhme et al. (https://doi.org/10.1007/s11538-017-0375-1) employed a center-based model. Here, the model is encoded in the standardized language MorpheusML. ...

In the experimental paradigm of CCl4 intoxication of mice, hepatocytes around the central vein (located in the center of an idealized hexagonal liver lobule) are dying and are subsequently replaced by new hepatocytes, largely through activation of proliferation in the remaining hepatocytes.

Alignment of daughter hepatocytes along the orientation of the closest sinusoid, a process which is named hepatocyte-sinusoid alignment (HSA), was proposed by Höhme et al. (https://doi.org/10.1073/pnas.0909374107) ...

This model was used in the Modeling Workshop at the 2nd LiSyM-Cancer Status Seminar.

SOP Western diet mouse housing and feeding

Empty SOP template based on nature protocol format and reqiremeents

Liver is the major site for glycogen storage. Glycogen content can be significantly altered upon disruption of glucose homeostasis in metabolic syndromes, such as diabetes.

Glycogen content can be determined by an acid-hydrolysis method . Basically, glucose, the hydrolysis product of glycogen, is converted into glucose-6- phosphate (G-6-P) by hexokinase in the presence of ATP.

With the supply of NADP, G-6-P is further converted into 6-phosphogluconic acid by G-6-P dehydrogenase (G-6-PDH), while ...

SOP: Mice hepatocytes isolation and co-cultivation with BMDM

This protocol details the RNAseq sample preparation starting with mRNA and ending with quality control of finished libraries. This protocol was used specifically for virus mRNA samples related to ORFeome lab group.

Isolation of primary mouse hepatocytes

As a member of LiSyM-Cancer you already have a “profile” in LiSyM SEEK, i.e. your name and mail address is known to the system. You now have to register or in other words create a user name and a password. Download and watch the the short tutorial on how this works.

Multicellular simulations have become indispensable in understanding complex biological phenomena, from tissue development to disease progression. The diversity of simulation methods (including cellular Potts, cellular automata, lattice-free, stochastic particle and other methodologies) and the lack of standards for multicellular model specification pose challenges to building reproducible, modular and reusable simulations.

This competition is designed to promote and support the development of ...

BioModels has launched a new competition for early career researchers, to recognize emerging leaders in systems biology modelling, identify exciting modelling research and promote reproducibility and good modelling practice.

Am I eligible?

The competition is aimed at early career researchers, including but not limited to PhD students, postdocs, staff scientists, and research assistants, who have published a peer-reviewed scientific manuscript with a mechanistic mathematical model or machine ...

The “Computational Modeling in Biology” Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology, synthetic biology and related fields. HARMONY is a codefest-type meeting, with a focus on development of the standards, interoperability and infrastructure. There are generally not many general discussions or oral presentations during HARMONY; instead, the time is devoted to allowing hands-on hacking and interaction between ...

The “Computational Modeling in Biology” Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology and related fields. COMBINE 2024 is a workshop-style event with oral presentations, breakout sessions and tutorials. The three meeting days will include talks about the COMBINE standards and associated or related standardization efforts, presentations of tools using these standards, breakout sessions for detailed discussions as ...

Sessions:

• From single cell analysis to clinical application
• Mechanistic modeling at the cellular scale proposing intervention strategies
• Tissue scale modeling and organ communication in systems medicine
• AI contributions to systems medicine - Diagnosis and therapy monitoring
• The future of systems biology

The “Computational Modeling in Biology” Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology, synthetic biology and related fields. HARMONY is a codefest-type meeting, with a focus on development of the standards, interoperability and infrastructure. There are generally not many general discussions or oral presentations during HARMONY; instead, the time is devoted to allowing hands-on hacking and interaction between ...

Just over 30 years ago, the cellular Potts model (CPM) was introduced to explain experimental observations of spontaneous cell sorting in embryonic tissue cultures. In the years since, the CPM evolved into a powerful model framework for simulating a wide range of physical and biological processes – from foam physics to tissue development, cancer growth, angiogenesis, plant development, evolution, immune responses, and cell migration. Having just celebrated the 30th birthday of the CPM, now is a ...

The “Computational Modeling in Biology” Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology and related fields. COMBINE 2023 is a workshop-style event with oral presentations, breakout sessions and tutorials. The three meeting days will include talks about the COMBINE standards and associated or related standardization efforts, presentations of tools using these standards, breakout sessions for detailed discussions as ...

The Computational Modeling in Biology Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology, synthetic biology and related fields. HARMONY is a codefest-type meeting, with a focus on development of the standards, interoperability and infrastructure. There are generally not many general discussions or oral presentations during HARMONY; instead, the time is devoted to allowing hands-on hacking and interaction between people ...

The “Computational Modeling in Biology” Network (COMBINE) is an initiative to coordinate the development of the various community standards and formats in systems biology and related fields. COMBINE 2022 will be a workshop-style event with oral presentations, breakout sessions and tutorials. The three meeting days will include talks about the COMBINE standards and associated or related standardization efforts, presentations of tools using these standards, breakout sessions for detailed discussions ...

Workshop #1 LiSym status seminar March 2023, Dresden “Towards concordant multiomics of liver”

Group picture from Lisym-Cancer Status Seminar 2023

Agreement on the Use of Personal Data during LiSyM-Cancer Young Scientists Retreat Date: 07.09. -09.09.2022 Place: Ev. Tagungsstätte Hofgeismar

Agenda for LiSyM-Cancer status seminar 2022

Agenda Kickoff Meeting SMART-NAFLD 1-2 december 2021 in Heidelberg