SysMedPD SIGNED
Systems Medicine of Mitochondrial Parkinson’s Disease
Total Cost €
0EC-Contrib. €
0Partnership
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0SysMedPD project word cloud
Explore the words cloud of the SysMedPD project. It provides you a very rough idea of what is the project "SysMedPD" about.
Project "SysMedPD" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITEIT LEIDEN
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | http://www.sysmedpd.eu |
| Total cost | 5˙999˙990 € |
| EC max contribution | 5˙999˙990 € (100%) |
| Programme |
1. H2020-EU.3.1.1. (Understanding health, wellbeing and disease) |
| Code Call | H2020-PHC-2015-two-stage |
| Funding Scheme | RIA |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-12-01 to 2020-11-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITEIT LEIDEN | NL (LEIDEN) | coordinator | 1˙201˙400.00 |
| 2 | UNIVERSITE DU LUXEMBOURG | LU (ESCH-SUR-ALZETTE) | participant | 1˙260˙965.00 |
| 3 | UNIVERSITAET zu LUEBECK | DE (LUBECK) | participant | 672˙512.00 |
| 4 | KHONDRION BV | NL (BEUNINGEN) | participant | 662˙500.00 |
| 5 | NATIONAL UNIVERSITY OF IRELAND MAYNOOTH | IE (Maynooth) | participant | 620˙220.00 |
| 6 | UNIVERSITY COLLEGE LONDON | UK (LONDON) | participant | 599˙978.00 |
| 7 | MIMETAS BV | NL (Leiden) | participant | 596˙050.00 |
| 8 | EURICE EUROPEAN RESEARCH AND PROJECT OFFICE GMBH | DE (ST INGBERT) | participant | 386˙363.00 |
Map
Project objective
The overall objective of this project is to identify novel drug candidates capable of slowing down the progression of neurodegeneration in the subset of Parkinson’s disease (PD) patients with overt mitochondrial dysfunction. Multi-modal phenotypic characterisation of cohorts of monogenic PD patients with overt mitochondrial dysfunction will be used as an anchor for the discovery of two extreme cohorts of idiopathic PD patients: with and without detectable mitochondrial dysfunction. A suite of personalised in vitro, in vivo, and in silico models will be generated using induced pluripotent stem cells (iPSCs) from selected subjects and controls. An industrial quality 3D microfluidic cell culture product, specifically designed for the culture of iPSC-derived dopaminergic neurons, will be developed for use in a morphological and bioanalytical screen for lead compounds reduce mitochondrial dysfunction. By monitoring motor behaviour and in situ striatal neurochemistry at high temporal resolution, the in vivo response to lead compounds will be characterised in humanised mouse models with striatally transplants of iPSC-derived dopaminergic neurons derived from PD patients. Personalised computational models of dopaminergic neuronal metabolism and mitochondrial morphology will be developed. These in silico models will be used to accelerate drug development by prioritising pathways for metabolomic assay optimisation, stratifying idiopathic PD patients by degree of mitochondrial dysfunction, predicting new new targets to reduce mitochondrial dysfunction and mechanistic interpretation in vitro and in vivo experimental results. SysMedPD unites a highly experienced multidisciplinary consortium in an ambitious project to develop and apply a systems biomedicine approach to preclinically identify candidate neuroprotectants, for the estimated 1-2 million people worldwide who suffer from PD with mitochondrial dysfunction.
Deliverables
| SysMedPD audio-visual material | Other | 2020-02-25 10:58:32 |
| Successful differentiation of dopaminergic neurons from iPSCs and subsequent transplantation into NOD SCID mice | Documents, reports | 2020-02-25 10:58:32 |
| Successful neurochemical analysis performed in transplanted SCID mice and correlation to phenotype progression investigated | Documents, reports | 2020-02-25 10:58:32 |
| Miniaturised metabolomics platform including storage device for sample transport | Demonstrators, pilots, prototypes | 2020-02-25 10:58:32 |
| External project website | Websites, patent fillings, videos etc. | 2020-02-25 10:58:31 |
| Draft mitochondrial molecular network reconstruction | Demonstrators, pilots, prototypes | 2020-02-25 10:58:31 |
| Metabolomics platform for mitochondrial dysfunction | Demonstrators, pilots, prototypes | 2020-02-25 10:58:30 |
| Characterisation of in vivo amperometric sensors and microdialysis in the striatum of mice | Documents, reports | 2020-02-25 10:58:30 |
Take a look to the deliverables list in detail: detailed list of SysMedPD deliverables.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2019 |
Jonas Walter, Silvia Bolognin, Paul M.A. Antony, Sarah L. Nickels, Suresh K. Poovathingal, Luis Salamanca, Stefano Magni, Rita Perfeito, Fredrik Hoel, Xiaobing Qing, Javier Jarazo, Jonathan Arias-Fuenzalida, Tomasz Ignac, Anna S. Monzel, Laura Gonzalez-Cano, Luis Pereira de Almeida, Alexander Skupin, Karl J. Tronstad, Jens C. Schwamborn Neural Stem Cells of Parkinson\'s Disease Patients Exhibit Aberrant Mitochondrial Morphology and Functionality published pages: 878-889, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2019.03.004 |
Stem Cell Reports 12/5 | 2020-02-25 |
| 2019 |
Lisa M. Smits, Stefano Magni, Kamil Grzyb, Paul MA. Antony, Rejko Krüger, Alexander Skupin, Silvia Bolognin, Jens C. Schwamborn Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids published pages: , ISSN: , DOI: 10.1101/589598 |
2020-02-25 | |
| 2019 |
Cornelius C.W. Willacey, Martijn Naaktgeboren, Edinson Lucumi Moreno, Agnieszka B. Wegrzyn, Daan van der Es, Naama Karu, Ronan M.T. Fleming, Amy C. Harms, Thomas Hankemeier LC–MS/MS analysis of the central energy and carbon metabolites in biological samples following derivatization by dimethylaminophenacyl bromide published pages: 460413, ISSN: 0021-9673, DOI: 10.1016/j.chroma.2019.460413 |
Journal of Chromatography A 1608 | 2020-02-25 |
| 2019 |
Lisa M. Smits, Lydia Reinhardt, Peter Reinhardt, Michael Glatza, Anna S. Monzel, Nancy Stanslowsky, Marcelo D. Rosato-Siri, Alessandra Zanon, Paul M. Antony, Jessica Bellmann, Sarah M. Nicklas, Kathrin Hemmer, Xiaobing Qing, Emanuel Berger, Norman Kalmbach, Marc Ehrlich, Silvia Bolognin, Andrew A. Hicks, Florian Wegner, Jared L. Sterneckert, Jens C. Schwamborn Modeling Parkinson’s disease in midbrain-like organoids published pages: , ISSN: 2373-8057, DOI: 10.1038/s41531-019-0078-4 |
npj Parkinson\'s Disease 5/1 | 2020-02-25 |
| 2019 |
Javier Jarazo, Xiaobing Qing, Jens C. Schwamborn Guidelines for Fluorescent Guided Biallelic HDR Targeting Selection With PiggyBac System Removal for Gene Editing published pages: , ISSN: 1664-8021, DOI: 10.3389/fgene.2019.00190 |
Frontiers in Genetics 10 | 2020-02-25 |
| 2019 |
Khalid I. W. Kane, Edinson Lucumi Moreno, Siham Hachi, Moriz Walter, Javier Jarazo, Miguel A. P. Oliveira, Thomas Hankemeier, Paul Vulto, Jens C. Schwamborn, Martin Thoma, Ronan M. T. Fleming Automated microfluidic cell culture of stem cell derived dopaminergic neurons published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-34828-3 |
Scientific Reports 9/1 | 2020-02-25 |
| 2019 |
Laurent Heirendt, Sylvain Arreckx, Thomas Pfau, Sebastián N. Mendoza, Anne Richelle, Almut Heinken, Hulda S. Haraldsdóttir, Jacek Wachowiak, Sarah M. Keating, Vanja Vlasov, Stefania Magnusdóttir, Chiam Yu Ng, German Preciat, Alise Žagare, Siu H. J. Chan, Maike K. Aurich, Catherine M. Clancy, Jennifer Modamio, John T. Sauls, Alberto Noronha, Aarash Bordbar, Benjamin Cousins, Diana C. El Assal, Luis V. Valcarcel, Iñigo Apaolaza, Susan Ghaderi, Masoud Ahookhosh, Marouen Ben Guebila, Andrejs Kostromins, Nicolas Sompairac, Hoai M. Le, Ding Ma, Yuekai Sun, Lin Wang, James T. Yurkovich, Miguel A. P. Oliveira, Phan T. Vuong, Lemmer P. El Assal, Inna Kuperstein, Andrei Zinovyev, H. Scott Hinton, William A. Bryant, Francisco J. Aragón Artacho, Francisco J. Planes, Egils Stalidzans, Alejandro Maass, Santosh Vempala, Michael Hucka, Michael A. Saunders, Costas D. Maranas, Nathan E. Lewis, Thomas Sauter, Bernhard Ø. Palsson, Ines Thiele, Ronan M. T. Fleming Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0 published pages: 639-702, ISSN: 1754-2189, DOI: 10.1038/s41596-018-0098-2 |
Nature Protocols 14/3 | 2020-02-25 |
| 2017 |
Miguel A. P. Oliveira, Rudi Balling, Marten P. Smidt, Ronan M. T. Fleming Embryonic development of selectively vulnerable neurons in Parkinson’s disease published pages: , ISSN: 2373-8057, DOI: 10.1038/s41531-017-0022-4 |
npj Parkinson\'s Disease 3/1 | 2020-02-25 |
| 2017 |
Alberto Noronha, Anna Dröfn DanÃelsdóttir, Piotr Gawron, Freyr Jóhannsson, SoffÃa Jónsdóttir, Sindri Jarlsson, Jón Pétur Gunnarsson, Sigurður Brynjólfsson, Reinhard Schneider, Ines Thiele, Ronan M. T. Fleming ReconMap: an interactive visualization of human metabolism published pages: btw667, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/btw667 |
Bioinformatics | 2020-02-25 |
| 2016 |
Maike K. Aurich, Ronan M. T. Fleming, Ines Thiele MetaboTools: A Comprehensive Toolbox for Analysis of Genome-Scale Metabolic Models published pages: , ISSN: 1664-042X, DOI: 10.3389/fphys.2016.00327 |
Frontiers in Physiology 7 | 2020-02-25 |
| 2017 |
Oliveira, Miguel Selective vulnerability in Parkinson\'s disease: contributions from neuronal connectivity, lineage and functional identity published pages: , ISSN: , DOI: |
2020-02-25 | |
| 2017 |
Jonathan Arias-Fuenzalida, Javier Jarazo, Xiaobing Qing, Jonas Walter, Gemma Gomez-Giro, Sarah Louise Nickels, Holm Zaehres, Hans Robert Schöler, Jens Christian Schwamborn FACS-Assisted CRISPR-Cas9 Genome Editing Facilitates Parkinson\'s Disease Modeling published pages: 1423-1431, ISSN: 2213-6711, DOI: 10.1016/j.stemcr.2017.08.026 |
Stem Cell Reports 9/5 | 2020-02-25 |
| 2017 |
V. van Duinen, A. van den Heuvel, S. J. Trietsch, H. L. Lanz, J. M van Gils, A. J. van Zonneveld, P. Vulto, T. Hankemeier 96 perfusable blood vessels to study vascular permeability in vitro published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-14716-y |
Scientific Reports 7/1 | 2020-02-25 |
| 2019 |
Silvia Bolognin, Marie Fossépré, Xiaobing Qing, Javier Jarazo, Janez Å ÄanÄar, Edinson Lucumi Moreno, Sarah L. Nickels, Kobi Wasner, Nassima Ouzren, Jonas Walter, Anne Grünewald, Enrico Glaab, Luis Salamanca, Ronan M. T. Fleming, Paul M. A. Antony, Jens C. Schwamborn 3D Cultures of Parkinson\'s Disease-Specific Dopaminergic Neurons for High Content Phenotyping and Drug Testing published pages: 1800927, ISSN: 2198-3844, DOI: 10.1002/advs.201800927 |
Advanced Science 6/1 | 2020-02-25 |
| 2018 |
Laura Gonzalez-Cano, Ingeborg Menzl, Johan Tisserand, Sarah Nicklas, Jens C. Schwamborn Parkinson’s Disease-Associated Mutant LRRK2-Mediated Inhibition of miRNA Activity is Antagonized by TRIM32 published pages: 3490-3498, ISSN: 0893-7648, DOI: 10.1007/s12035-017-0570-y |
Molecular Neurobiology 55/4 | 2020-02-25 |
| 2017 |
German A. Preciat Gonzalez, Lemmer R. P. El Assal, Alberto Noronha, Ines Thiele, Hulda S. Haraldsdóttir, Ronan M. T. Fleming Comparative evaluation of atom mapping algorithms for balanced metabolic reactions: application to Recon 3D published pages: , ISSN: 1758-2946, DOI: 10.1186/s13321-017-0223-1 |
Journal of Cheminformatics 9/1 | 2020-02-25 |
| 2017 |
Schwamborn, Jens; Hemmer, Kathrin; Smits, Lisa; Bolognin, Silvia In Vivo Phenotyping Of Parkinson-Specific Stem Cells Reveals Increased a-Synuclein Levels But No Spreading published pages: , ISSN: , DOI: 10.1101/140178 |
2020-02-25 | |
| 2018 |
Jarazo, Javier The Parkinson’s Disease Associated Pink1-Parkin Pathway In Pathology And Development published pages: , ISSN: , DOI: |
2020-02-25 | |
| 2017 |
Vasudev Kantae, Elke H. J. Krekels, Michiel J. Van Esdonk, Peter Lindenburg, Amy C. Harms, Catherijne A. J. Knibbe, Piet H. Van der Graaf, Thomas Hankemeier Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy published pages: , ISSN: 1573-3882, DOI: 10.1007/s11306-016-1143-1 |
Metabolomics 13/1 | 2020-02-25 |
| 2017 |
Caroline H. Reid, Niall J. Finnerty Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study published pages: 1596, ISSN: 1424-8220, DOI: 10.3390/s17071596 |
Sensors 17/7 | 2020-02-25 |
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