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PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Overview

PoLiMeR is funded through the EU Marie Skłodowska-Curie Innovative Training Network (ITN), which drives scientific excellence and innovation. ITNs bring together universities, research institutes, industry and clinical partners from across the world to train researchers to doctorate level.

Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease progression and treatment response. A Systems Medicine approach, based on computational models fed with individual patient data, has the potential to provide the basis for a personalised diagnosis and treatment strategy. The PoLiMeR consortium (Polymers in the Liver: Metabolism and Regulation) has identified the inherited, liver-related diseases of glycogen and lipid metabolism as the ideal starting point for innovative research training in personalised ‘Systems Medicine'.

Programme: This Project is not associated with a Programme

SEEK ID: https://fairdomhub.org/projects/130

Public web page: http://polimer-itn.eu/

Organisms: Homo sapiens

FAIRDOM PALs: No PALs for this Project

Project created: 6th Dec 2018

Related items

Kishore Alagere Krishnamurthy

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

Institutions: University of Groningen

Barbara Bakker project_administrator

Projects: SilicoTryp, Multiscale modelling of state transitions in the host-microbiome-brain network, MESI-STRAT, PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Institutions: University of Groningen

https://orcid.org/0000-0001-6274-3633
Flavio Bonanini

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

Institutions: Mimetas

Terry G.J. Derks

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

Institutions: University of Leiden

Oliver Ebenhöh

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

Institutions: University of Duesseldorf

Gaia Fancellu

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

Institutions: John Innes Centre

Robert Field

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

Institutions: John Innes Centre

Ronan Fleming

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

Institutions: University of Leiden

Stephan Goetz

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

Institutions: Iceni Diagnostics Ltd

Thomas Hankemeier

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

Institutions: University of Leiden

Nazli Kara

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

Institutions: KTH Royal Institute of Technology

Ligia Akemi Kiyuna

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

Institutions: University Medical Centre Groningen

https://orcid.org/0000-0002-9872-2102
Olga Krebs adminproject_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: SysMO DB, FAIRDOM, ICYSB 2015 - International Practical Course in Systems Biology, ZucAt, SysMO-LAB, Kinetics on the move - Workshop 2016, Example use cases, FAIRDOM user meeting, ErasysApp Funders, EraCoBiotech 2 nd call proposal preparation, Service to URV Tarragona, Spain with respect to their Safety Assessment of Endocrine Disrupting Chemicals model (Active NOW), FAIRDOM & LiSyM & de.NBI Data Structuring Training, MESI-STRAT, INCOME, Multiscale modelling of state transitions in the host-microbiome-brain network, BESTER, TRALAMINOL, Sustainable co-production, INDIE - Biotechnological production of sustainable indole, Extremophiles metabolsim, PoLiMeR - Polymers in the Liver: Metabolism and Regulation, GB-XMap: Assessing the risk of gut-brain cross-diseases Investigating the gut-brain-axis, NAD COMPARTMENTATION, HOTSOLUTE, Stress granules

Institutions: Heidelberg Institute for Theoretical Studies (HITS gGmbH), FAIRDOM User meeting, Norwegian University of Science and Technology

https://orcid.org/0000-0003-3540-0402
Dorota Kurek

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

Institutions: Mimetas

Adil Mardinoglu

Projects: IMOMESIC, HUMET Startup, PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Institutions: Chalmers University of Technology

Wolfgang Müller project_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: SysMO DB, FAIRDOM, ICYSB 2015 - International Practical Course in Systems Biology, de.NBI-SysBio, Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF - Pillar III), Early Metabolic Injury (LiSyM-EMI - Pillar I), Chronic Liver Disease Progression (LiSyM-DP - Pillar II), LiSyM Core Infrastructure and Management (LiSyM-PD), Liver Function Diagnostics (LiSyM-LiFuDi - Pillar IV), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Kinetics on the move - Workshop 2016, Example use cases, SBEpo - Systems Biology of Erythropoietin, FAIRDOM & LiSyM & de.NBI Data Structuring Training, MESI-STRAT, INCOME, EnzymeML, PoLiMeR - Polymers in the Liver: Metabolism and Regulation, MS_DILI, GMDS Project Group "FAIRe Dateninfrastrukturen für die Biomedizinische Informatik"

Institutions: Heidelberg Institute for Theoretical Studies (HITS gGmbH)

https://orcid.org/0000-0002-4980-3512
Siti Nurjanah

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

Institutions: University of Freiburg

Christoff Odendaal

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

Institutions: University Medical Centre Groningen

Maaike H. Oosterveer

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

Institutions: University of Groningen

https://orcid.org/0000-0003-4117-7833
Adelaide Raguin

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

Institutions: University of Duesseldorf

Chalmers University of Technology

Country:  Sweden

City: Gothenburg

Web page: http://www.chalmers.se/en/

Heidelberg Institute for Theoretical Studies (HITS gGmbH)

Country:  Germany

City: Heidelberg

Web page: http://www.h-its.org/

Heinrich Heine University of Düsseldorf

Country:  Germany

City: Düsseldorf

Web page: http://www.biologie.hhu.de/institute-und-abteilungen/pflanzengenetik/leitung-institut.html

Iceni Diagnostics Ltd

Country:  GB

City: Norwich

Web page: http://www.icenidiagnostics.com/company/

John Innes Centre

Country:  GB

City: Norwich

Web page: https://www.jic.ac.uk/

KTH Royal Institute of Technology

Country:  SE

City: STOCKHOLM

Web page: https://www.kth.se/en

Mimetas

Country:  NL

City: Leiden

Web page: https://mimetas.com/

University Medical Centre Groningen

Country:  Netherlands

City: Not specified

Web page: Not specified

University Of Innsbruck

Country:  AT

City: Innsbruck

Web page: https://www.uibk.ac.at/

University of Bergen

Country:  Norway

City: Not specified

Web page: Not specified

University of Duesseldorf

Country:  Germany

City: Not specified

Web page: Not specified

University of Freiburg

Country:  Germany

City: Freiburg

Web page: http://www.uni-freiburg.de/

University of Groningen

Country:  Netherlands

City: Groningen

Web page: http://www.rug.nl/corporate/index

University of Leiden

Country:  Netherlands

City: Not specified

Web page: Not specified

University of Luxembourg

Country:  Luxembourg

City: Not specified

Web page: http://wwwen.uni.lu/

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Translational Targeted Proteomics Profiling of Mitochondrial Energy Metabolic Pathways in Mouse and Human Samples.
PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Abstract (Expand)

Absolute measurements of protein abundance are important in the understanding of biological processes and the precise computational modeling of biological pathways. We developed targeted LC-MS/MS assays … in the selected reaction monitoring (SRM) mode to quantify over 50 mitochondrial proteins in a single run. The targeted proteins cover the tricarboxylic acid cycle, fatty acid beta-oxidation, oxidative phosphorylation, and the detoxification of reactive oxygen species. Assays used isotopically labeled concatemers as internal standards designed to target murine mitochondrial proteins and their human orthologues. Most assays were also suitable to quantify the corresponding protein orthologues in rats. After exclusion of peptides that did not pass the selection criteria, we arrived at SRM assays for 55 mouse, 52 human, and 51 rat proteins. These assays were optimized in isolated mitochondrial fractions from mouse and rat liver and cultured human fibroblasts and in total liver extracts from mouse, rat, and human. The developed proteomics approach is suitable for the quantification of proteins in the mitochondrial energy metabolic pathways in mice, rats, and humans as a basis for translational research. Initial data show that the assays have great potential for elucidating the adaptive response of human patients to mutations in mitochondrial proteins in a clinical setting.

Authors: J. C. Wolters, J. Ciapaite, K. van Eunen, K. E. Niezen-Koning, A. Matton, R. J. Porte, P. Horvatovich, Barbara Bakker, R. Bischoff, H. P. Permentier

Date Published: No date defined

Journal: J Proteome Res

A systems study reveals concurrent activation of AMPK and mTOR by amino acids.
PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Abstract (Expand)

Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known … about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational-experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes.

Authors: P. Dalle Pezze, S. Ruf, A. G. Sonntag, M. Langelaar-Makkinje, P. Hall, A. M. Heberle, Patricia Razquin Navas, K. van Eunen, R. C. Tolle, J. J. Schwarz, H. Wiese, B. Warscheid, J. Deitersen, B. Stork, E. Fassler, S. Schauble, U. Hahn, P. Horvatovich, Daryl Shanley, Kathrin Thedieck

Date Published: No date defined

Journal: Nat Commun

Hepatocytes contribute to residual glucose production in a mouse model for glycogen storage disease type Ia.
PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Abstract (Expand)

It is a long-standing enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production despite the loss of glucose-6-phosphatase activity. Insight … into the source of residual endogenous glucose production is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated glucose-6-phosphatase-independent endogenous glucose production in hepatocytes isolated from a liver-specific GSD Ia mouse model (L-G6pc(-/-) mice) and performed real-time analysis of hepatic glucose fluxes and glycogen metabolism in L-G6pc(-/-) mice using state-of-the-art stable isotope methodologies. Here we show that G6pc-deficient hepatocytes are capable of producing glucose. In vivo analysis of hepatic glucose metabolism revealed that the hepatic glucokinase flux was decreased by 95% in L-G6pc(-/-) mice. It also showed increased glycogen phosphorylase flux in L-G6pc(-/-) mice, which is coupled to the release of free glucose through glycogen debranching. Although the ex vivo activities of debranching enzyme and lysosomal acid maltase, two major hepatic alpha-glucosidases, were unaltered in L-G6pc(-/-) mice, pharmacological inhibition of alpha-glucosidase activity almost completely abolished residual glucose production by G6pc-deficient hepatocytes. CONCLUSION: Our data indicate that hepatocytes contribute to residual glucose production in GSD Ia. We show that alpha-glucosidase activity, i.e. glycogen debranching and/or lysosomal glycogen breakdown, contributes to residual glucose production by GSD Ia hepatocytes. A strong reduction in hepatic GCK flux in L-G6pc-/- mice furthermore limits the phosphorylation of free glucose synthesized by G6pc-deficient hepatocytes, allowing the release of glucose into the circulation. The almost complete abrogation of GCK flux in G6pc-deficient liver also explains the contradictory reports on residual glucose production in GSD Ia patients. (Hepatology 2017;66:2042-2054).

Authors: B. S. Hijmans, A. Boss, T. H. van Dijk, M. Soty, H. Wolters, E. Mutel, Bert Groen, T. G. J. Derks, G. Mithieux, A. Heerschap, D. J. Reijngoud, F. Rajas, M. H. Oosterveer

Date Published: No date defined

Journal: Hepatology

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Python presentation by Adelaide Raguin, Friday May 31st
PoLiMeR - Polymers in the Liver: Metabolism and Regulation

Slides for the Python Workshop

Creator: Oliver Ebenhöh

Contributor: Oliver Ebenhöh

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