PoLiMeR_user Martines_data project_administrator

Projects: PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Institutions: Heidelberg Institute for Theoretical Studies (HITS gGmbH)

Nhung Pham

Projects: EmPowerPutida, COVID-19 Disease Map

Institutions: Wageningen University & Research, University Maastricht

https://orcid.org/0000-0003-3091-3962
Madlen Matz-Soja project_administratorasset_housekeeperasset_gatekeeper

Projects: The Hedgehog Signalling Pathway (LiSyM-JGMMS)

Institutions: Universität Leipzig - Medizinische Fakultät - Institut für Biochemie

Joerg Heeren

Projects: HUMET Startup

Institutions: University Medical Center Hamburg - Eppendorf Hamburg

Sander Kersten

Projects: HUMET Startup

Institutions: Wageningen University & Research

https://orcid.org/0000-0003-4488-7734
Eduard Kerkhoven project_administrator

Projects: SilicoTryp, SYSTERACT, SynBio4Flav

Institutions: University of Glasgow, Chalmers University of Technology

https://orcid.org/0000-0002-3593-5792
jean-charles portais

Projects: MetApp

Institutions: INSA Toulouse

EbN1 stoichiometric model iAA835 (Metano)

This stoichiometric model of Aromatoleum aromaticum EbN1 is a genome-scale model and comprises 655 enzyme-catalyzed reactions and 731 distinct metabolites.

The model is in the plain-text reaction format of Metano that is human-readable and can be opened with every text editor. To run this version of the model, please use the Metano Modeling Toolbox (mmtb.brenda-enzymes.org) and the associated scenario files.

Creators: Julia Koblitz, Dietmar Schomburg, Meina Neumann-Schaal

Submitter: Julia Koblitz

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The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation

Abstract (Expand)

Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that … control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. We test three candidate mechanisms for the accumulation of these organic acids. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits. This work updates the first biorXiv version, February 2017,with an expanded description and additional analysis of the same core data sets and the same FMv2 model, summary tables and supporting, follow-on data from three further studies with further collaborators. This biorXiv revision constitutes the second version of this report.

Authors: Yin Hoon Chew, Daniel D. Seaton, Virginie Mengin, Anna Flis, Sam T. Mugford, Gavin M. George, Michael Moulin, Alastair Hume, Samuel C. Zeeman, Teresa B. Fitzpatrick, Alison M. Smith, Mark Stitt, Andrew J. Millar

Date Published: 6th Feb 2017

Publication Type: Tech report

Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

Abstract (Expand)

L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders … ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative. This Review summarizes the physiological and pathophysiological roles of Trp metabolism, highlighting the vast opportunities and challenges for drug development in multiple diseases. Full text of this paper is available here https://inrepo01.inet.dkfz-heidelberg.de/record/143705

Authors: Michael Platten, Ellen A. A. Nollen, Ute F. Röhrig, Francesca Fallarino, Christiane A. Opitz

Date Published: 1st May 2019

Publication Type: Journal

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