Deliverables
A report summarizing results from fluorescence-based assays.
Constructs and protocols for priority SLCsSet of expression vectors and protein purification protocols for SLCs on the priority list.
Transcriptome and metabolome for priority SLCsQuantitative differential transcriptome, metabolome data within a cell line that naturally expresses each SLC in the priority list in both basal and stimuli challenged states.
Data Management Plan 2Initial version of DMP after 6 months, an updated version latest mid-term and a final version
Vector generationCollection of lentiviral and Flp-In compatible vectors carrying CRISPR-based Cas9 and sgRNAs targeting all SLCs, together with vectors carrying tagged and untagged cDNAs for >80% of the SLC family
ReSOLUTE knowledgebaseConcept for database of integrated publicly available knowledge and ReSOLUTE web portal.
Data MiningData mining support for priority ranking of SLC family members for target selection in WP4.
Informatic anylysis of metabolomic dataDevelopment and deployment of workflows for QSAR analysis of the ability of particular overexpressed SLCs to take up different substrates, and judicious variation of those substrates.
SLC overexpression in HEK293Collection of >300 HEK293 isogenic cell lines, each overexpressing a SLC gene, quality-controlled and characterized with a multi-parameter approach
DEP implemented (stepwise, up to M60)Subcellular localization of target SLCs
Based on optical imaging experiments with tagged SLCs.
SLC overexpressing cell linesCollection of 600 cell lines each overexpressing a specific SLC in untagged and tagged versions qualitycontrolled and characterized with a multiparameter approach
SLC interactomePhysical measurement (by proteomics) of coexpression/copurification of SLCs with partners.
Signature metabolic profiles using targeted metabolomicsRobust identification and quantification using LCGCMS for some 180 central metabolites
SLC Interactome for priority SLCsCondition dependent protein interaction network data in response to on-target and orthogonal pathway stimuli modulating SLC function.
Profile of plasma metabolite changes for each SLC cell lineUse of methods of Task 2.2 to assess the largest changes between cells lines upregulated/knocked out for particular SLCs
Assays for SLCs based on SSM-electrophysiologyA report summarizing results and protocols obtained with the SURFE2R approach.
Production of validated SLC antibodiesLarge set of validated antibodies targeting SLCs, together with tissue localization data.
Assays for SLCs based on fluorescent sensor proteinsA report summarizing results and protocols on measuring SLC-dependent metabolic states through fluorescent sensor proteins.
Production of antigens and high-affinity bindersAntigens for animal immunization for priority SLCs, together with DARPins or monobodies for priority SLCS and a panel of relevant SLCs.
SLC k.o. cell linesCollection of 600 cell lines each carrying frameshift mutations in one SLC gene qualitycontrolled and characterized with a multiparameter approach
Assays for SLCs based on cell lines that couple growth to SLC functionA report summarizing results and protocols on assay based on genetic engineering of cell lines dependent on specific SLCs for survival.
Assays for SLCs based on mass spectrometry, thermal shift, radiolabelled or fluorescent compoundsA report summarizing results from classical transport assays.
Assays for (electrogenic) transportersA report summarizing results and protocols obtained using fluorescent sensitive dyes and impedance measurements.
Physiological and physical network map for priority SLCsCondition-dependent regulatory models integrating transcriptomics, metabolomics and proteomics data for priority SLCs.
Data Management Plan 3Initial version of DMP after 6 months, an updated version latest mid-term and a final version
Methodology for general detection of plasma metabolites and drug/dietary componentsLC/GC-MS coupled to novel deconvolution routines for determining the approximately 3,000 molecules typically observable in serum
Protein expression screenA family-wide assessment of protein expression yields in recombinant expression systems.
Determination of SLCs using ions as (co-)substratesThe recognition that many substrates are symporters or antiporters means that one can detect this by assessing the movement of co-ions when transport substrates are added to suitable cell lines.
SLC genetic interaction mapProduction of ‘synthetic phenotypes’, based on the principle that knocking out both variants of a transporter with redundant function (e.g. loss of ability to transport X) thereby causes a phenotype from which one can infer function.
SLC k.o. in HEK293Collection of 300 HEK293 isogenic cell lines each carrying frameshift mutations in a SLC gene qualitycontrolled and characterized with a multiparameter approach
Reconstitution of SLCs in proteoliposomes and nanodiscsNanodisc- and liposome-reconstituted SLCs for in vitro assays of successfully purified SLCs of the priority list.
Data Management Plan 1Initial version of DMP after 6 months, an updated version latest mid-term and a final version.
Protein production for the SLCs in the priority listProduction of milligram quantities of highly pure (>90%) and stable protein samples for >30% of the priority SLCs.
Data sharing and approval process, and prototype of interface for data access at public web portal up and running
ReSOLUTE databaseInfrastructure and data warehouse for sharing annotated raw data files and analysis results; prototype ready after first year and annual releases of new versions.
Publications
Author(s):
Gelová, Zuzana; Ingles-Prieto, Alvaro
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462234
Author(s):
Ulrich Goldmann, Gerhard Ecker, Vitaly Sedlyarov, Lia Scarabottolo, Vania Manolova, Claire Colas
Published in:
2020
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179816
Author(s):
Lia Scarabottolo; Juergen Reinhardt; Huub Sijben
Published in:
2020
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179859
Author(s):
Ulrich Goldmann; Vitaly Sedlyarov; Daniela Digles; Barbara Füzi
Published in:
2018
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179834
Author(s):
Goldmann, Ulrich; Ecker, Gerhard; Sedlyarov, Vitaly; Scarabottolo, Lia; Manolova, Vania; Colas, Claire
Published in:
Issue 1, 2019
Publisher:
n/a
DOI:
10.5281/zenodo.4309586
Author(s):
Gernot Wolf; Klaus Seuwen; Barbara Barbosa; Eirini Christodoulaki; Alvaro Ingles-Prieto; Ulrich Goldmann; Christoph Klimek; Svenja Onstein; Vitaly Sedlyarov; Tabea Wiedmer; Diana Santacruz; Coralie Viollet; Florence Massey; Veeranagouda Yaligara
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.10419148
Author(s):
Viollet, Coralie; Santacruz, Diana; Knebel, Dagmar; Rust, Werner; Acker, Susanne; Dick, Alec
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462292
Author(s):
David B. Sauer; Huanyu Li; Sagar Raturi; Andreea Scacioc; Tina Bohstedt; Abilasha Balakrishnan
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462714
Author(s):
Svenja Onstein; Eva Liñeiro; Christoph Klimek; Barbara Barbosa; Gernot Wolf
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7457377
Author(s):
Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733107
Author(s):
Sauer, David B.; Huanyu Li; Raturi, Sagar; Scacioc, Andreea; Bohstedt, Tina; Abilasha Balakrishnan
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7462743
Author(s):
Daniela Digles; Jiani Li; Ulrich Goldmann
Published in:
2018
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179841
Author(s):
Alvaro Ingles-Prieto; Felix Kartnig
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7457392
Author(s):
Eva Liñeiro; Alvaro Ingles-Prieto; Fabian Frommelt; André C. Mueller
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462207
Author(s):
Wolf, Gernot; Seuwen, Klaus
Published in:
2021
Publisher:
n/a
DOI:
10.5281/zenodo.5566804
Author(s):
Sauer, David B.; Huanyu Li; Raturi, Sagar; Scacioc, Andreea; Bohstedt, Tina; Abilasha Balakrishnan
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462911
Author(s):
Pfeifer, Martin; Kohlbrenner, Mariah; Chang, Lena; Lambrigger, Pascal; Ingles-Prieto, Alvaro; Reinhardt, Jürgen
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7457345
Author(s):
Klimek, Christoph; Onstein, Svenja; Barbosa, Barbara; Ingles-Prieto, Alvaro; Skucha, Anna; Ibig, Yvonne; Seuwen, Klaus; Wolf, Gernot
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7457220
Author(s):
David B. Sauer; Huanyu Li; Sagar Raturi; Andreea Scacioc; Tina Bohstedt; Abilasha Balakrishnan
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462780
Author(s):
Alshafie, Walaa; Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733134
Author(s):
David B. Sauer; Huanyu Li; Sagar Raturi; Andreea Scacioc; Tina Bohstedt; Abilasha Balakrishnan
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462876
Author(s):
Gernot Wolf; Alvaro Ingles-Prieto; Enrico Girardi; Vitaly Sedlyarov; Svenja Onstein; Christoph Klimek; Barbara Barbosa
Published in:
2019
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179824
Author(s):
Philipp Leippe; Lia Scarabottolo
Published in:
2020
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179857
Author(s):
Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733132
Author(s):
Klimek, Christoph; Onstein, Svenja; Barbosa, Barbara; Wolf, Gernot
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462188
Author(s):
Gernot Wolf; Klaus Seuwen; Barbara Barbosa; Eirini Christodoulaki; Alvaro Ingles-Prieto; Ulrich Goldmann; Christoph Klimek; Svenja Onstein; Vitaly Sedlyarov; Tabea Wiedmer; Diana Santacruz; Coralie Viollet
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.10419229
Author(s):
Tabea Wiedmer; Abigail Jarret; Sabrina Lindinger
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462174
Author(s):
Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733123
Author(s):
Svenja Onstein; Christoph Klimek; Barbara Barbosa; Anna Skucha; Gernot Wolf
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7457297
Author(s):
Alvaro Ingles-Prieto; Eva Liñeiro; Ariel Bensimon; Fabian Frommelt; André C. Mueller
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7457416
Author(s):
Eva Liñeiro; André C. Mueller
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7462271
Author(s):
Claire Steppan; Marina Wright Muelas; Douglas Kell; Tabea Wiedmer; Mary Piotrowski
Published in:
2019
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179870
Author(s):
David B. Sauer; Huanyu Li; Sagar Raturi; Andreea Scacioc; Tina Bohstedt; Abilasha Balakrishnan
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7468558
Author(s):
Ulrich Goldmann; Vitaly Sedlyarov
Published in:
2019
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179880
Author(s):
Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733103
Author(s):
Ingles-Prieto, Alvaro; Liñeiro, Eva; Frommelt, Fabian
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7457436
Author(s):
Ulrich Goldmann; Vitaly Sedlyarov
Published in:
2019
Publisher:
Zenodo
DOI:
10.5281/zenodo.5179889
Author(s):
Tabea Wiedmer, Eirini Christodoulaki, Sabrina Lindinger, Iciar Serrano, Christoph Bueschl, Thomas Hannich
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.10419241
Author(s):
Gernot Wolf; Klaus Seuwen; Barbara Barbosa; Eirini Christodoulaki; Alvaro Ingles-Prieto; Ulrich Goldmann; Christoph Klimek; Svenja Onstein; Vitaly Sedlyarov; Tabea Wiedmer; Diana Santacruz; Coralie Viollet; Florence Massey; Veeranagouda Yaligara
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.10419196
Author(s):
Mueller, André C.; Liñeiro, Eva
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7462252
Author(s):
Garcia, Julio; Gelova, Zuzana
Published in:
2023
Publisher:
n/a
DOI:
10.5281/zenodo.10033541
Author(s):
Vera Pütter; Yung-Ning Chang
Published in:
2022
Publisher:
Zenodo
DOI:
10.5281/zenodo.7468532
Author(s):
Christoph Klimek; Svenja Onstein; Barbara Barbosa; Alvaro Ingles-Prieto; Anna Skucha; Gernot Wolf
Published in:
2022
Publisher:
n/a
DOI:
10.5281/zenodo.7457295
Author(s):
Ayoubi, Riham; McPherson, Peter S.; Laflamme, Carl
Published in:
2021
Publisher:
Zenodo
DOI:
10.5281/zenodo.4733121
Author(s):
Diana Santacruz, Francis O Enane, Katrin Fundel-Clemens, Martin Giner, Gernot Wolf, Svenja Onstein, Christoph Klimek, Zachary Smith, Bhagya Wijayawardena, Coralie Viollet
Published in:
SLAS Discovery, 2022, ISSN 2472-5552
Publisher:
Elsevier
DOI:
10.1016/j.slasd.2022.01.002
Author(s):
Granulo N, Sosnin S, Digles D, Ecker G.
Published in:
Molecular Informatics, 2024, ISSN 1868-1743
Publisher:
Wiley - VCH Verlag GmbH & CO. KGaA
DOI:
10.1002/minf.202300287
Author(s):
Mocking TAM, Sijben HJ, Vermeulen YW, IJzerman AP, Heitman LH
Published in:
International Journal of Molecular Sciences, 2022, ISSN 1422-0067
Publisher:
Multidisciplinary Digital Publishing Institute (MDPI)
DOI:
10.3390/ijms23031203
Author(s):
Evandro Ferrada, Tabea Wiedmer, Wen-An Wang, Fabian Frommelt, Barbara Steurer, Christoph Klimek, Sabrina Lindinger, Tanja Osthushenrich, Andrea Garofoli, Silvia Brocchetti, Samuel Bradberry, Jiahui Huang, Aidan MacNamara, Lia Scarabottolo, Gerhard F. Ecker, Anders Malarstig, Giulio Superti-Furga
Published in:
Journal of Molecular Biology, 2024, ISSN 0022-2836
Publisher:
Academic Press
DOI:
10.1016/j.jmb.2023.168383
Author(s):
Polesel M, Ingles-Prieto A, Christodoulaki E, Ferrada E, Doucerain C, Altermatt P, Knecht M, Kuhn M, Steck AL, Wilhelm M, Manolova V.
Published in:
Biometals, 2023, ISSN 0966-0844
Publisher:
Kluwer Academic Publishers
DOI:
10.1007/s10534-022-00474-6
Author(s):
Raturi S, Li H, Chang YN, Scacioc A, Bohstedt T, Fernandez-Cid A, Evans A, Abrusci P, Balakrishnan A, Pascoa TC, He D, Chi G, Kaur Singh N, Ye M, Li A, Shrestha L, Wang D, Williams EP, Burgess-Brown NA, Dürr KL, Puetter V, Ingles-Prieto A, Sauer DB.
Published in:
Journal of Visualized Experiments, 2023, ISSN 1940-087X
Publisher:
MYJoVE Corporation
DOI:
10.3791/65878
Author(s):
Vojtech Dvorak, Tabea Wiedmer, Alvaro Ingles-Prieto, Patrick Altermatt, Helena Batoulis, Felix Bärenz, Eckhard Bender, Daniela Digles, Franz Dürrenberger, Laura H. Heitman, Adriaan P. IJzerman, Douglas B. Kell, Stefanie Kickinger, Daniel Körzö, Philipp Leippe, Thomas Licher, Vania Manolova, Riccardo Rizzetto, Francesca Sassone, Lia Scarabottolo, Avner Schlessinger, Vanessa Schneider, Hubert J.
Published in:
Frontiers in Pharmacology, Issue 12, 2021, ISSN 1663-9812
Publisher:
Frontiers Media S.A.
DOI:
10.3389/fphar.2021.722889
Author(s):
Vojtech Dvorak & Giulio Superti-Furga
Published in:
Expert Opinion on Drug Discovery, 2023, ISSN 1746-0441
Publisher:
Informa Healthcare
DOI:
10.1080/17460441.2023.2244760
Author(s):
Eva Meixner, Ulrich Goldmann, Vitaly Sedlyarov, Stefania Scorzoni, Manuele Rebsamen, Enrico Girardi, Giulio Superti‐Furga
Published in:
Molecular Systems Biology, Issue 16/7, 2020, ISSN 1744-4292
Publisher:
Nature Publishing Group
DOI:
10.15252/msb.20209652
Author(s):
Hubert J. Sijben, Wieke M. van Oostveen, Peter B. R. Hartog, Laura Stucchi, Andrea Rossignoli, Giovanna Maresca, Lia Scarabottolo, Adriaan P. IJzerman, Laura H. Heitman
Published in:
Scientific Reports, Issue 11/1, 2021, ISSN 2045-2322
Publisher:
Nature Publishing Group
DOI:
10.1038/s41598-021-91700-7
Author(s):
Hubert J. Sijben, Giulio Superti-Furga, Adriaan P. IJzerman, Laura H. Heitman
Published in:
Trends in Pharmacological Sciences, 2022, ISSN 0165-6147
Publisher:
Elsevier BV
DOI:
10.1016/j.tips.2022.02.004
Author(s):
Tabea Wiedmer, Alvaro Ingles-Prieto, Ulrich Goldmann, Claire M. Steppan, Giulio Superti-Furga, the RESOLUTE, REsolution consortia
Published in:
Clinical Pharmacology & Therapeutics, Issue 00099236, 2022, ISSN 0009-9236
Publisher:
Nature Publishing Group
DOI:
10.1002/cpt.2639
Author(s):
Pommereau, A., Licher, T., & Bärenz, F.
Published in:
Current Protocols, 2023, ISSN 2691-1299
Publisher:
Wiley
DOI:
10.1002/cpz1.650
Author(s):
Brandon J. Bongers, Huub J. Sijben, Peter B. R. Hartog, Andrey Tarnovskiy, Adriaan P. IJzerman, Laura H. Heitman, and Gerard J. P. van Westen
Published in:
Journal of Chemical Information and Modeling, 2023, ISSN 1549-9596
Publisher:
American Chemical Society
DOI:
10.1021/acs.jcim.2c01645
Author(s):
Claire Colas, Giulia Banci, Riccardo Martini, Gerhard F. Ecker
Published in:
Scientific Reports, Issue 10/1, 2020, ISSN 2045-2322
Publisher:
Nature Publishing Group
DOI:
10.1038/s41598-020-63189-z
Author(s):
Claire Colas
Published in:
Frontiers in Pharmacology, 2020, ISSN 1663-9812
Publisher:
Frontiers Media S.A.
DOI:
10.3389/fphar.2020.01229
Author(s):
Sijben HJ, Dall’ Acqua L, Liu R, Jarret A, Christodoulaki E, Onstein S, Wolf G, Verburgt SJ, Le Dévédec SE, Wiedmer T, Superti-Furga G, IJzerman AP and Heitman LH
Published in:
Frontiers in Pharmacology, 2022, ISSN 1663-9812
Publisher:
Frontiers Media S.A.
DOI:
10.3389/fphar.2022.872335
Author(s):
Hubert J. Sijben, Julie J. E. van den Berg, Jeremy D. Broekhuis, Adriaan P. IJzerman, Laura H. Heitman
Published in:
Scientific Reports, Issue 11/1, 2021, ISSN 2045-2322
Publisher:
Nature Publishing Group
DOI:
10.1038/s41598-020-79218-w
Author(s):
Manuele Rebsamen, Enrico Girardi, Vitaly Sedlyarov, Stefania Scorzoni, Konstantinos Papakostas, Manuela Vollert, Justyna Konecka, Bettina Guertl, Kristaps Klavins, Tabea Wiedmer, Giulio Superti-Furga
Published in:
Life Science Alliance, Issue 25751077, 2022, ISSN 2575-1077
Publisher:
Life Science Alliance, LLC
DOI:
10.26508/lsa.202201404
Author(s):
Giulio Superti-Furga, Daniel Lackner, Tabea Wiedmer, Alvaro Ingles-Prieto, Barbara Barbosa, Enrico Girardi, Ulrich Goldmann, Bettina Gürtl, Kristaps Klavins, Christoph Klimek, Sabrina Lindinger, Eva Liñeiro-Retes, André C. Müller, Svenja Onstein, Gregor Redinger, Daniela Reil, Vitaly Sedlyarov, Gernot Wolf, Matthew Crawford, Robert Everley, David Hepworth, Shenping Liu, Stephen Noell, Mary Pio
Published in:
Nature Reviews Drug Discovery, Issue 19/7, 2020, Page(s) 429-430, ISSN 1474-1776
Publisher:
Nature Publishing Group
DOI:
10.1038/d41573-020-00056-6
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