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Ursula Klingmüller

About Ursula Klingmüller:
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SEEK ID: https://fairdomhub.org/people/474

Location:  Germany

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Chronic Liver Disease Progression (LiSyM-DP - Pillar II)
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Programme: LiSyM - Systems Medicine of the Liver

Public web page: Not specified

Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III)
No description specified

Programme: LiSyM - Systems Medicine of the Liver

Public web page: Not specified

MS_DILI
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Programme: MS_DILI

Public web page: Not specified

IMOMESIC

IMOMESIC - Integrating Modelling of Metabolism and Signalling towards an Application in Liver Cancer

One of the most challenging questions in cancer research is currently the interconnection of metabolism and signalling. An understanding of mechanisms that facilitate the physiological shift towards a proliferative metabolism in cancer cells is considered a major upcoming topic in oncology and is a key activity for future drug development. Due to the complexity of interrelations, a systems biology
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Programme: ERASysAPP

Public web page: Not specified

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Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis
IMOMESIC

Abstract (Expand)

Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to … replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.

Authors: Avlant Nilsson, Jurgen R. Haanstra, Martin Engqvist, Albert Gerding, Barbara M. Bakker, Ursula Klingmüller, Bas Teusink, Jens Nielsen

Date Published: 27th Apr 2020

Publication Type: Journal

Excemplify: a flexible template based solution, parsing and managing data in spreadsheets for experimentalists.
SBEpo - Systems Biology of Erythropoietin

Abstract (Expand)

In systems biology, quantitative experimental data is the basis of building mathematical models. In most of the cases, they are stored in Excel files and hosted locally. To have a public database for … collecting, retrieving and citing experimental raw data as well as experimental conditions is important for both experimentalists and modelers. However, the great effort needed in the data handling procedure and in the data submission procedure becomes the crucial limitation for experimentalists to contribute to a database, thereby impeding the database to deliver its benefit. Moreover, manual copy and paste operations which are commonly used in those procedures increase the chance of making mistakes. Excemplify, a web-based application, proposes a flexible and adaptable template-based solution to solve these problems. Comparing to the normal template based uploading approach, which is supported by some public databases, rather than predefining a format that is potentiall impractical, Excemplify allows users to create their own experiment-specific content templates in different experiment stages and to build corresponding knowledge bases for parsing. Utilizing the embedded knowledge of used templates, Excemplify is able to parse experimental data from the initial setup stage and generate following stages spreadsheets automatically. The proposed solution standardizes the flows of data traveling according to the standard procedures of applying the experiment, cuts down the amount of manual effort and reduces the chance of mistakes caused by manual data handling. In addition, it maintains the context of meta-data from the initial preparation manuscript and improves the data consistency. It interoperates and complements RightField and SEEK as well.

Authors: L. Shi, L. Jong, U. Wittig, P. Lucarelli, M. Stepath, S. Mueller, L. A. D'Alessandro, U. Klingmuller, W. Muller

Date Published: 3rd Apr 2013

Publication Type: Journal

Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range
Molecular Systems Biology

Abstract (Expand)

Cellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. The specific contributions of individual feedback regulators, however, remain unclear. Based … on extensive time-resolved data sets in primary erythroid progenitor cells, we established a dynamic pathway model to dissect the roles of the two transcriptional negative feedback regulators of the suppressor of cytokine signaling (SOCS) family, CIS and SOCS3, in JAK2/STAT5 signaling. Facilitated by the model, we calculated the STAT5 response for experimentally unobservable Epo concentrations and provide a quantitative link between cell survival and the integrated response of STAT5 in the nucleus. Model predictions show that the two feedbacks CIS and SOCS3 are most effective at different ligand concentration ranges due to their distinct inhibitory mechanisms. This divided function of dual feedback regulation enables control of STAT5 responses for Epo concentrations that can vary 1000-fold in vivo. Our modeling approach reveals dose-dependent feedback control as key property to regulate STAT5-mediated survival decisions over a broad range of ligand concentrations.

Authors: J. Bachmann, A. Raue, M. Schilling, M. E. Bohm, C. Kreutz, D. Kaschek, H. Busch, N. Gretz, W. D. Lehmann, J. Timmer, U. Klingmuller

Date Published: 2011

Publication Type: Not specified

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