30.01.2018 | Webinar: The SURFE²R Technology: Assays for Parmacological and Functional Characterization of Membrane Transporters
SURFE²R 96SE and SURFE²R N1
This webinar gives you an overview on the SURFE²R technology and its applications. Furthermore, we invited Dr. Thomas Licher (Sanofi Germany) as speaker, to present his work and experiences on the SURFE²R 96SE device.
Dr. Maria Barthmes, Product Manager SURFE²R product family, Nanion Technologies GmbH
Maria explains the solid supported membrane (SSM)-based methodology and gives a brief introduction on our two devices, the SURFE²R 96SE and the SURFE²R N1.
Dr. Andre Bazzone, Application Scientist, Nanion Technologies GmbH
Andre is an expert in the field of SSM-based electrophysiology: He made his PhD at the Max-Planck-Institute of Biophysics in Frankfurt, Germany on the electrophysiological characterization of sugar transporters using the SSM-based electrophysiology in 2016. Right afterwards, he started as Application Scientist at Nanion Technologies and today he is an important member of the Nanion SURFE²R team.
Electrophysiological Characterization of sugar transporters using SSM-based electrophysiology
SSM-based electrophysiology helps to understand the mechanisms of different transporters. The technique was used to characterize and compare different sugar transporters and their transport deficient mutants. Proton-coupled (LacY, XylE, FucP), sodium-coupled (MelB) and loosely coupled (GlcP) sugar transporters were analyzed. A general transport model was concluded from the electrophysiological data. Here we present the most intriguing results for these transporters as well as our conclusions regarding the transport mechanism. We will discuss (1) substrate specifity, (2) protonation and coupling mechanisms, (3) the impact of different driving forces, (4) sugar binding kinetics and (5) the significance of specific amino acids for the transport cycle. All together SSM-based electrophysiology helped to conclude a detailed kinetic model for sugar transporters.
Dr. Thomas Licher, Head of in vitro Biology & High-Throughput Chemistry, Sanofi, IDD Frankfurt, Germany
Thomas made his PhD at the Center for Molecular Neurobiology in the group of Prof. Dr. Pongs on an HTS-technology for ion channel-modulating substances in 2002. He started to work for Sanofi-Aventis, later Sanofi as Post-doc, lab head and group leader in the field for Cardiac Safety and Lead Identification Technologies. Today, Thomas is Head of in vitro Biology & High-Throughput Chemistry at Sanofi in Frankfurt, Germany.
Pharmacological characterization of an amino acid transporter and his bacterial homologue – a case study using the SURFE²R 96SE technology
Ion channels and membrane transporters are involved in multiple (patho)physiological processes and are recognized as a growing therapeutic target class. Analysis of these proteins is challenging because of the limited availability of proper assays for efficient compound screening.
The IDD in vitro biology department in Frankfurt has a long tradition of transporter drug discovery. We apply a comprehensive repertory to identify new small molecules to modulate transporter function, resulting in several successful applications in lead optimization.
For a Na+-dependent amino-acid transporter, a recent target of Sanofi, no direct assays for pharmacological characterization were available. This target is important in two indications relevant for Sanofi and a screening cascade for identification of small molecule inhibitors was established. The Sanofi compound library was screened with a fluorescence-based membrane potential assay and actives were validated with a MS-based substrate flux assay. To validate the hits an electrophysiological assay was required. We evaluated the SURFE²R 96SE workstation, as a solid supported membrane (SSM) based electrophysiological technique, to assess transporter activity. We established an assay for automated direct recording of transporter mediated currents and successfully integrated the SURFE²R technology into the screening tree for hit validation.