Voigt, Niels

[["dc.bibliographiccitation.artnumber","898717"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","15"],["dc.contributor.affiliation","Rosholm, Kadla R.; 1Sophion Bioscience A/S, Ballerup, Denmark"],["dc.contributor.affiliation","Badone, Beatrice; 1Sophion Bioscience A/S, Ballerup, Denmark"],["dc.contributor.affiliation","Karatsiompani, Stefania; 1Sophion Bioscience A/S, Ballerup, Denmark"],["dc.contributor.affiliation","Nagy, David; 2Sophion Bioscience Inc., Woburn, MA, United States"],["dc.contributor.affiliation","Seibertz, Fitzwilliam; 3Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Voigt, Niels; 3Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany"],["dc.contributor.affiliation","Bell, Damian C.; 1Sophion Bioscience A/S, Ballerup, Denmark"],["dc.contributor.author","Rosholm, Kadla R."],["dc.contributor.author","Badone, Beatrice"],["dc.contributor.author","Karatsiompani, Stefania"],["dc.contributor.author","Nagy, David"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Bell, Damian C."],["dc.date.accessioned","2022-07-07T06:30:05Z"],["dc.date.available","2022-07-07T06:30:05Z"],["dc.date.issued","2022-06-22"],["dc.date.updated","2022-07-06T16:07:27Z"],["dc.description.abstract","In the Hollywood blockbuster “The Curious Case of Benjamin Button” a fantastical fable unfolds of a man’s life that travels through time reversing the aging process; as the tale progresses, the frail old man becomes a vigorous, vivacious young man, then man becomes boy and boy becomes baby. The reality of cellular time travel, however, is far more wondrous: we now have the ability to both reverse and then forward time on mature cells. Four proteins were found to rewind the molecular clock of adult cells back to their embryonic, “blank canvas” pluripotent stem cell state, allowing these pluripotent stem cells to then be differentiated to fast forward their molecular clocks to the desired adult specialist cell types. These four proteins – the “Yamanaka factors” – form critical elements of this cellular time travel, which deservedly won Shinya Yamanaka the Nobel Prize for his lab’s work discovering them. Human induced pluripotent stem cells (hiPSCs) hold much promise in our understanding of physiology and medicine. They encapsulate the signaling pathways of the desired cell types, such as cardiomyocytes or neurons, and thus act as model cells for defining the critical ion channel activity in healthy and disease states. Since hiPSCs can be derived from any patient, highly specific, personalized (or stratified) physiology, and/or pathophysiology can be defined, leading to exciting developments in personalized medicines and interventions. As such, hiPSC married with high throughput automated patch clamp (APC) ion channel recording platforms provide a foundation for significant physiological, medical and drug discovery advances. This review aims to summarize the current state of affairs of hiPSC and APC: the background and recent advances made; and the pros, cons and challenges of these technologies. Whilst the authors have yet to finalize a fully functional time traveling machine, they will endeavor to provide plausible future projections on where hiPSC and APC are likely to carry us. One future projection the authors are confident in making is the increasing necessity and adoption of these technologies in the discovery of the next blockbuster, this time a life-enhancing ion channel drug, not a fantastical movie."],["dc.identifier.doi","10.3389/fnmol.2022.898717"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112401"],["dc.language.iso","en"],["dc.relation.eissn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Adventures and Advances in Time Travel With Induced Pluripotent Stem Cells and Automated Patch Clamp"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Jung, Philipp"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Fakuade, Funsho E."],["dc.contributor.author","Ignatyeva, Nadezda"],["dc.contributor.author","Sampathkumar, Shrivatsan"],["dc.contributor.author","Ritter, Melanie"],["dc.contributor.author","Li, Housen"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Ebert, Antje"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2022-05-24T06:53:38Z"],["dc.date.available","2022-05-24T06:53:38Z"],["dc.date.issued","2022-05-02"],["dc.description.abstract","Dilated cardiomyopathy (DCM) is a major risk factor for heart failure and is associated with the development of life-threatening cardiac arrhythmias. Using a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model harbouring a mutation in cardiac troponin T (R173W), we aim to examine the cellular basis of arrhythmogenesis in DCM patients with this mutation. iPSC from control (Ctrl) and DCM-TnT-R173W donors from the same family were differentiated into iPSC-CM and analysed through optical action potential (AP) recordings, simultaneous measurement of cytosolic calcium concentration ([Ca2+]i) and membrane currents and separately assayed using field stimulation to detect the threshold for AP- and [Ca2+]i-alternans development. AP duration was unaltered in TnT-R173W iPSC-CM. Nevertheless, TnT-R173W iPSC-CM showed a strikingly low stimulation threshold for AP- and [Ca2+]i-alternans. Myofilaments are known to play a role as intracellular Ca2+ buffers and here we show increased Ca2+ affinity of intracellular buffers in TnT-R173W cells, indicating increased myofilament sensitivity to Ca2+. Similarly, EMD57033, a myofilament Ca2+ sensitiser, replicated the abnormal [Ca2+]i dynamics observed in TnT-R173W samples and lowered the threshold for alternans development. In contrast, application of a Ca2+ desensitiser (blebbistatin) to TnT-R173W iPSC-CM was able to phenotypically rescue Ca2+ dynamics, normalising Ca2+ transient profile and minimising the occurrence of Ca2+ alternans at physiological frequencies. This finding suggests that increased Ca2+ buffering likely plays a major arrhythmogenic role in patients with DCM, specifically in those with mutations in cardiac troponin T. In addition, we propose that modulation of myofilament Ca2+ sensitivity could be an effective anti-arrhythmic target for pharmacological management of this disease."],["dc.identifier.doi","10.1007/s00395-022-00912-z"],["dc.identifier.pmid","35499658"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108251"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/430"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/482"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1435-1803"],["dc.relation.issn","0300-8428"],["dc.relation.workinggroup","RG Ebert (Cardiovascular Cell Biology and Systems Medicine)"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.rights","CC BY 4.0"],["dc.title","Increased cytosolic calcium buffering contributes to a cellular arrhythmogenic substrate in iPSC-cardiomyocytes from patients with dilated cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","982316"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","15"],["dc.contributor.affiliation","Rapedius, Markus; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Obergrussberger, Alison; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Humphries, Edward S. A.; 2Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom"],["dc.contributor.affiliation","Scholz, Stephanie; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Rinke-Weiss, Ilka; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Goetze, Tom A.; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Brinkwirth, Nina; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Rotordam, Maria Giustina; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Strassmaier, Tim; 3Nanion Technologies Inc., Livingston, NJ, United States"],["dc.contributor.affiliation","Randolph, Aaron; 3Nanion Technologies Inc., Livingston, NJ, United States"],["dc.contributor.affiliation","Friis, Søren; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.affiliation","Liutkute, Aiste; 4Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany"],["dc.contributor.affiliation","Seibertz, Fitzwilliam; 4Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany"],["dc.contributor.affiliation","Voigt, Niels; 4Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Georg-August University, Göttingen, Germany"],["dc.contributor.affiliation","Fertig, Niels; 1Nanion Technologies GmbH, Munich, Germany"],["dc.contributor.author","Rapedius, Markus"],["dc.contributor.author","Obergrussberger, Alison"],["dc.contributor.author","Humphries, Edward S. A."],["dc.contributor.author","Scholz, Stephanie"],["dc.contributor.author","Rinke-Weiss, Ilka"],["dc.contributor.author","Goetze, Tom A."],["dc.contributor.author","Brinkwirth, Nina"],["dc.contributor.author","Rotordam, Maria Giustina"],["dc.contributor.author","Strassmaier, Tim"],["dc.contributor.author","Randolph, Aaron"],["dc.contributor.author","Fertig, Niels"],["dc.contributor.author","Friis, Søren"],["dc.contributor.author","Liutkute, Aiste"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2022-10-04T10:22:01Z"],["dc.date.available","2022-10-04T10:22:01Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:15:06Z"],["dc.description.abstract","Fluoride has been used in the internal recording solution for manual and automated patch clamp experiments for decades because it helps to improve the seal resistance and promotes longer lasting recordings. In manual patch clamp, fluoride has been used to record voltage-gated Na (Na\r\n V\r\n ) channels where seal resistance and access resistance are critical for good voltage control. In automated patch clamp, suction is applied from underneath the patch clamp chip to attract a cell to the hole and obtain a good seal. Since the patch clamp aperture cannot be moved to improve the seal like the patch clamp pipette in manual patch clamp, automated patch clamp manufacturers use internal fluoride to improve the success rate for obtaining GΩ seals. However, internal fluoride can affect voltage-dependence of activation and inactivation, as well as affecting internal second messenger systems and therefore, it is desirable to have the option to perform experiments using physiological, fluoride-free internal solution. We have developed an approach for high throughput fluoride-free recordings on a 384-well based automated patch clamp system with success rates >40% for GΩ seals. We demonstrate this method using hERG expressed in HEK cells, as well as Na\r\n V\r\n 1.5, Na\r\n V\r\n 1.7, and K\r\n Ca\r\n 3.1 expressed in CHO cells. We describe the advantages and disadvantages of using fluoride and provide examples of where fluoride can be used, where caution should be exerted and where fluoride-free solutions provide an advantage over fluoride-containing solutions."],["dc.identifier.doi","10.3389/fnmol.2022.982316"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114567"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5099"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","There is no F in APC: Using physiological fluoride-free solutions for high throughput automated patch clamp experiments"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]