| dc.contributor.advisor | Voigt, Niels Prof. Dr. | |
| dc.contributor.author | Seibertz, Fitzwilliam | |
| dc.date.accessioned | 2023-08-22T15:52:05Z | |
| dc.date.available | 2024-06-07T00:50:07Z | |
| dc.date.issued | 2023-08-22 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14847 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-10066 | |
| dc.format.extent | 164 Seiten | de |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 610 | |
| dc.title | High throughput strategies for electrophysiological characterisation of cardiomyocytes | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Meyer, Thomas Prof. Dr. | |
| dc.date.examination | 2023-06-08 | de |
| dc.description.abstracteng | Personalised medicine describes the customised application of medical treatment at
a patient-specific level. This type of precision medicine stratifies patients based on
their specific genotype or phenotype for targeted therapy. For treatment of
cardiovascular disorders, this is not yet clinically feasible due to high monetary costs
and the slow rate at which molecular disease mechanisms are determined and
treatment modalities can be tested. Scalable cellular models such as induced
pluripotent stem cell derived cardiomyocyte technology (iPSC-CM) are required for
widespread use, along with a concomitant increase in high throughput measurement
strategies for robust assessment of cardiac function. This work aims to demonstrate
how state-of-the-art high throughput electrophysiological methods can be successfully
implemented into basic science research and could aid future implementation
strategies for patient-specific care. Herein, three peer-reviewed and published articles
deeply analyse cardiomyocyte function using novel high throughput
electrophysiological methods. Using specialised voltage and calcium sensitive dyes in
single cells, Article I elegantly identifies and targets a novel arrhythmogenic
mechanism in iPSC-CM derived from a patient with genetic dilated cardiomyopathy.
Such fluorescent dyes provide accurate and non-invasive readouts of cellular
membrane voltage and cytosolic calcium concentration, respectively. Article II
contains the first known measurements of primary cardiomyocytes using a market-
leading high throughput automated patch-clamp (APC) device. Revolutionary in
automating the typically complex and experimenter dependent patch-clamp technique,
APC is only now beginning to migrate into academic institutions with wider user
applications. Article III utilises multiple measurement modalities including APC and in
silico techniques to model age-related variability in iPSC-CM technology and assess
the suitability of the construct for mechanistic studies and compound screening in the
development of personalised medicine paradigms. | de |
| dc.contributor.coReferee | Rizzoli, Silvio Prof. Dr. | |
| dc.contributor.thirdReferee | Griesinger, Christian Prof. Dr. | |
| dc.contributor.thirdReferee | Salditt, Tim Prof. Dr. | |
| dc.contributor.thirdReferee | Moser, Tobias Prof. Dr. | |
| dc.contributor.thirdReferee | Freichel, Marc Prof. Dr. | |
| dc.subject.ger | Automated patch clamp | de |
| dc.subject.ger | Cardiac | de |
| dc.subject.ger | Electrophysiology | de |
| dc.subject.ger | Stem cells | de |
| dc.subject.eng | Automated patch clamp | de |
| dc.subject.eng | Cardiac | de |
| dc.subject.eng | Electrophysiology | de |
| dc.subject.eng | Stem cells | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14847-1 | |
| dc.affiliation.institute | Medizinische Fakultät | |
| dc.subject.gokfull | OK-MEDIZIN | de |
| dc.description.embargoed | 2024-06-07 | de |
| dc.identifier.ppn | 1857714911 | |
| dc.identifier.orcid | 0000-0002-8554-5186 | de |
| dc.notes.confirmationsent | Confirmation sent 2023-08-22T19:45:01 | de |