Biophysical Society 63rd Annual Meeting | Program Guide

Room 301: Monday, March 4

12:30 PM – 2:00 PM Nanion Technologies Ion Channels and Transporters in the Spotlight

10:30 AM – 12:00 PM Bruker Corporation Using NMR (Nuclear Magnetic Resonance) and EPR (Electron Paramagnetic Resonance) in Biophysics Magnetic resonance offers many insights into how biological systems function. The two techniques shed light on the identity of species, dynamics, and structures of proteins, peptides, nucleotides, and lipids. The speakers will present an overview of these techniques and applica- tions for people who may be new to the field and wish to incorporate them in their studies. NMR is a valuable tool for the study of structures and dynamic processes of proteins, peptides and nucleotides. NMR is also well suited to study the interaction of such molecules. Various NMR methods exist to study the interaction of proteins with small molecules in drug discovery, inter- actions of proteins with each other or with peptides and nucleotides. In drug discovery fragment based screening by NMR is a well-established technique. A brief presentation of these methods will be included. The investigation of interaction between larger molecules is facilitated by several NMR methods and by the use of isotopic labeling. Interactions such as protein oligomerization, protein-protein and proteinnucleotide interaction in solutions can be investigated. An overview of these tech- niques and applications will be included. In contrast to NMR, EPR detects unpaired electrons in free radicals and transition metal ions. One electron transfer reactions result in unpaired electrons. Examples of paramagnetic species encountered in biology are: • ROS (Reactive Oxygen Species), RNS (Reactive Nitrogen Species) • Amino acid radicals such as tyrosine and tryptophan radicals • Paramagnetic intermediates in photosynthesis • Metalloenzymes In addition to these naturally occurring paramagnetic species, spin labels can be incorporated into a number of biomolecules via SDSL (Site Directed Spin Labeling). Applications and techniques are: • Motional dynamics of proteins, peptides, and nucleotides via linse- hape analysis • Accessibility studies in membrane proteins or peptides via satura- tion measurements • Distance measurements (2-8 nm) via DEER (Double Electron- Electron Resonance) to complement other structural methods such as Xray, NMR, CryoEM and FRET An introduction to the techniques and applications will be presented. Speakers Ralph Weber, Senior Application Scientist, Bruker Corporation Clemens Anklin, Vice President Applications, Bruker Corporation

Nanion Technologies is the leading solution provider for electrophysi- ologists since 2002. If you are studying ion channels and electrogenic transporters, our chip- and plate-based devices are well suited to advance your research and screening projects. In our portfolio, you will find instrumentation for automated patch clamp, bilayer record- ings, SSM-based electrophysiology, impedance and extracellular field recordings, covering the needs for low, medium and high throughput assays. Our workshop will start with an introduction by Dr. Niels Fertig (CEO, Nanion) and Dr. Andrea Brüggemann (CSO, Nanion), as a guide through the overall capabilities of Nanion´s technology portfolio. In continuation, we will welcome our speakers, Dr. Jean-Francois Rolland (Axxam) and Prof. Dr. Randy Stockbridge (University of Michigan), among others. As a part of our workshop, Dr. Rolland will focus on his recent work on assay development in ion channel drug discovery, using the high throughput automated patch clamp screening platform, the SyncroPatch 384/768PE. Application areas of this powerful system, recording from up to 768 cells simultaneously, range from high throughput screening (HTS), cardiac safety assessment and efficacy screening, to the analysis of ion channel mutations. The SyncroPatch 384/768PE supports voltage- and current clamp recordings, tempera- ture control, and minimal cell usage. In addition to the use of stably transfected cell lines, more challenging cell assays including stem cell- derived cells, transiently transfected cells or primary cells can be used successfully. In this presentation Dr. Rolland will also discuss the highly promising approach of using optogenetics combined with automated patch clamp technology in HTS. This method, using light to modulate molecular events in a targeted manner in living cells, could lead to cheaper, faster and highly reliable assays, suitable for running the early steps of ion channels’ drug discovery programs, especially when com- bined to automated electrophysiology. Among others, data obtained from Axxam´s bPAC-HCN2 cell line that was successfully assayed on SyncroPatch 384PE, will be presented. In continuation, Dr. Stockbridge will be focused on electrogenic trans- porter assay technology, the SURFE2 R. The SURFE2 R N1 (single chan- nel) and SURFE2 R 96SE (96 channels) technologies enable label-free real time measurements of electrogenic transporter protein activity. Employing SSM (solid supported membrane)-based electrophysiology, the SURFE2 R instruments compensate for the low turnover rate of these proteins by measurement of up to 109 transporters in paral- lel. Dr. Stockbridge, as an expert in measuring membrane transport function, will present her recent data obtained on the SURFE2 R N1 instrument. She has undertaken a comparative mechanistic analysis to understand how drug export function evolved in the SMR (small mul- tidrug resistance) exporters family. This involved screening panels of potential substrates (drugs and other compounds) to understand how substrate specificity differs among the drug exporters, guanidinium exporters, and various evolutionary intermediates. The Nanion team is excited to meet you at our workshop. Join us to learn more about how our “smart tools for electrophysiologists” can help take your research to the next level! Speakers Andrea Brüggemann, CSO, Nanion Technologies Niels Fertig, CEO, Nanion Technologies Jean-Francois Rolland, Head of Electrophysiology, Axxam Randy Stockbridge, Assistant Professor, University of Michigan

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