If you are interested in supporting the LS² ICMT & Biophysics Joint Meeting 2024 and getting a great visibility for your company or institution, please contact the LS² Office at info@ls2.ch until 22 October to book your package!!

Fitzwilliam Seibertz (Nanion Technologies, will.seibertz@nanion.de) 

Title: Novel high throughput technologies in drug development

Modern drug development for neurological and cardiac therapies must rely on innovative technologies to overcome the classical limitations of typical preclinical cellular models. First, scalable cellular substrates that faithfully recapitulate human neuronal and cardiac physiology are required. Second, high-throughput measurement modalities are necessary to accurately measure cellular function and rapidly screen libraries of new or lead compounds. Induced pluripotent stem cell (iPSC) derived neuronal and cardiac models coupled with automated patch clamps are increasingly used to provide new solutions to accelerate drug discovery.

We describe the successful application of high throughput automated patch clamp techniques using the SyncroPatch 384 to scalable iPSC-derived neuron and cardiomyocyte models for comprehensive overviews of ion channel function and pharmacology. Recordings of neuronal NaV and KV ion channel currents are routinely captured with high success rates in iPSC-derived neurons. This technology is also readily applicable to cardiomyocyte models for the measurement of a large panel of ion channel targets including INa, Ito, ICa, L, IKr, and IK1. A contractile activity represents the summation of electrophysiological processes in cardiomyocytes. We also explore how deep high throughput investigation of cardiomyocyte contractility in vitro can provide efficient quantification of cardiac safety and toxicology profiles using the FLEXcyte 96 device.

High throughput automated patch clamp and contractility assays can be applied throughout the drug development pipeline, from target validation to assay development and eventual hit discovery and lead optimization. These approaches enhance the predictability of drug responses and reduce the reliance on animal models, leading to more efficient and safer therapeutic discoveries.

Daphne Jurriens (LUMICKS, Paalbergweg 3, 1105 AG, Amsterdam, E-mail: d.jurriens@lumicks.com)

Title: Optical tweezers and single molecules: how to control, manipulate and visualize biomolecular complexes in real-time

Imagine if you could directly see the location and dynamics of individual proteins binding to a single piece of DNA/RNA in real-time. What if you could hold a single protein and manipulate its structure to interrogate its conformational landscape? What if you could assemble your biological complex step by step and expose it to different buffer conditions to test your experimental hypotheses? 

With the LUMICKS C-Trap, the world’s first dynamic single-molecule microscope combining high-resolution optical tweezers, fluorescence microscopy, and advanced microfluidics in a truly integrated system, you can do all of this! We will illustrate how the dynamic single-molecule approach can shed light on a multitude of biological processes: from the mechanism of action of DNA-binding enzymes to protein folding and conformational changes, from membrane remodelling to cellular mechanics. 

These experiments show that technological advances in hybrid single-molecule methods can be turned into an easy-to-use and stable instrument enabling control, visualization and manipulation of single molecules in real-time. This gives researchers the power to directly prove molecular mechanisms, in ways not previously possible, allowing them to answer mechanistic questions faster.