Forschungsnetzwerk LiSyM-Krebs

LiSyM-Krebs ist ein nationales Forschungsnetz zur Früherkennung und Prävention von Leberkrebs, das unter Verwendung des systemmedizinischen Forschungsansatzes die komplexen, dynamischen Prozesse der Krankheitsprogression analysiert, um ausgehend von den Erkenntnissen aus dem Forschungsnetz LiSyM die Entstehung von Leberkrebs besser zu verstehen, vorherzusagen und im besten Fall sogar zu verhindern. LiSyM-Krebs setzt die erfolgreichen Forschungsaktivitäten der BMBF-Vorgängerprogramme ...

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.

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.

GEO data set

Wolf2023Hepatology Communications

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) ...

SOP Western diet mouse housing and feeding

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 ...

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.

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 ...

Young Scientists Retreat (YSR) will take place from September 7th to 9th in Hofgeismar (close to Kassel) (https://tagungsstaette-hofgeismar.de/). Participation is mandatory for all PhD students, MD students and Postdocs in SMART-NAFLD, C-TIP-HCC and DEEP-HCC

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