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SysMedPD SIGNED

Systems Medicine of Mitochondrial Parkinson’s Disease

Total Cost €

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EC-Contrib. €

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Partnership

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 SysMedPD 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.

anchor    personalised    detectable    situ    cells    neurons    million    progression    silico    cell    characterised    new    slowing    designed    modal    pluripotent    stem    ipsc    cohorts    microfluidic    dopaminergic    stratifying    biomedicine    temporal    prioritising    assay    reduce    resolution    bioanalytical    vitro    unites    degree    industrial    predicting    disease    mouse    compounds    motor    neurodegeneration    subjects    drug    humanised    pd    monitoring    extreme    3d    candidate    suite    overt    striatally    models    characterisation    transplants    patients    people    interpretation    parkinson    neurochemistry    optimisation    discovery    quality    controls    metabolomic    preclinically    candidates    vivo    neuroprotectants    morphology    metabolism    striatal    mechanistic    sysmedpd    neuronal    multidisciplinary    suffer    screen    idiopathic    experimental    accelerate    subset    culture    computational    dysfunction    mitochondrial    monogenic    ipscs    phenotypic    worldwide    morphological   

Project "SysMedPD" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITEIT LEIDEN 

Organization address
address: RAPENBURG 70
city: LEIDEN
postcode: 2311 EZ
website: www.universiteitleiden.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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

List of 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
List of publications.
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 Daníelsdóttir, Piotr Gawron, Freyr Jóhannsson, Soffía 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 Ščančar, 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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