2024 ANNUAL REPORT

| 87 | dots, semiconductor nanocrystals, voltage sensors • Fluorescence microscopy/spectroscopy, super-resolution microscopy • Mesoscopic systems Abstract The bioelectronics medicine vision aims to interface the central and peripheral nervous systems and correct aberrant neurological circuits by injecting correcting signals. As part of this vision, we aim to develop inorganic nanoparticles that selfinsert into the membranes of live neurons and optically report on changes in their membrane potentials. The technology we aim to develop will afford the real-time recording of neuronal circuit activity and open up vast opportunities in utilizing biomimetic artificial inorganic ‘membrane proteins’ for alternative energy generation, light harvesting, compartmentalized catalysis across membranes, and many others. As part of this vision, we have already developed voltage sensing nanoparticles (vsNPs) for non-invasive optical recording of membrane potential at the single particle and nanoscale level at multiple sites in a large field of view. vsNPs allow for ‘pointy,’ single particle voltage detection. However, they still face challenges, and additional improvements are needed before this new generation of sensors can be widely translated into neurophysiological applications. We are developing targetable membrane potential nanosensors (MPNs) that optically and non-invasively record MPs at multiple sites in a large field of view (FoV) of primary cultured neurons with single-particle brightness and voltage sensing capacity at the nanoscale. We searching for the ultimate nanometer-size particle suitable for site-specific voltage membrane sensing on the nanoscale. We, therefore, study and develop different systems. Single-particle membrane potential optical recordings from NDTF,Cy5-Ab-avidin complex targeting GABAAR and DPA in cultured cortical neurons. Publications 2023 and 2024 • Adan Marzouq, Lion Morgenstein, Carlos A Huang-Zhu, Shimon Yudovich, Ayelet Atkins, Asaf Grupi, Reid C Van Lehn, Shimon Weiss. “Long-Chain Lipids Facilitate Insertion of Large Nanoparticles into Membranes of Small Unilamellar Vesicles.” Langmuir, 2024. • Paul D Harris, Eitan Lerner, Alessandra Narducci, Christian Gebhardt, Shimon Weiss, Thorben Cordes. “Disentangling Conformational and Photophysical Dynamics in Single-Molecule FRET and PIFE Experiments with Multiparameter Photon-by-Photon Hidden Markov Modeling.” Biophysical Journal , 2024. • Hyunju Cho, Yumeng Liu, SangYoon Chung, Sowmya Chandrasekar, Shimon Weiss, Shu-ou Shan. “Dynamic Stability of Sgt2 Enables Selective and Privileged Client Handover in a Chaperone Triad.” Nature Communications, 2024. • Ganesh Agam, Christian Gebhardt, Milana Popara, Rebecca Mächtel,J ulian Folz, Benjamin Ambrose, Neharika Chamachi, S ang Yoon Chung, Timothy D Craggs, Marijn de Boer, Dina Grohmann, Taekjip Ha, Andreas Hartmann, J elle Hendrix, Verena Hirschfeld, Christian G Hübner, Thorsten Hugel, Dominik Kammerer, Hyun-Seo Kang, Achillefs N Kapanidis, Georg Krainer, Kevin Kramm, Edward A Lemke, E itan Lerner, Emmanuel Margeat, Kirsten Martens, Jens Michaelis, J aba Mitra, Gabriel G Moya Muñoz, Robert B Quast, Nicole C Robb, Michael Sattler, Michael Schlierf, Jonathan Schneider, Tim Schröder, Anna Sefer, Piau Siong Tan, Johann Thurn, Philip Tinnefeld, John van Noort, Shimon Weiss, Nicolas Wendler, Niels Zijlstra, Anders Barth, Claus AM Seidel, Don C Lamb, Thorben Cordes. “Reliability and Accuracy of Single-Molecule FRET Studies for Characterization of Structural Dynamics and Distances in Proteins.” Nature Methods, 2023. • Subhabrata Ghosh, Ulrich Ross, Anna M Chizhik, Yung Kuo, Byeong Guk Jeong, Wan Ki Bae, Kyoungwon Park, Jack Li, Dan Oron, Shimon Weiss, Jorg Enderlein, Alexey I Chizhik. “Excitation Intensity-Dependent Quantum Yield of Semiconductor Nanocrystals.” The Journal of Physical Chemistry Letters, 2023. • Debjit Roy, Xavier Michalet, Kiran Bharadwaj, Evan W Miller, Yijie Wang, Arjun Deb, Michael A Wayne, Claudio Bruschini, Edoardo Charbon, Mahbanoo Vakili, Robert Gunsalus, Robert T Clubb, Shimon Weiss. “Towards Precise Optical Measurements of Steady State of and Small Changes in Resting Membrane Potentials.” Biophysical Journal , 2023. Prof. Yaari Gur Faculty of Engineering Lab for Computational Systems Immunology Research Areas • Computational • Immunology systems biology • Machine learning Abstract We are a data science-driven lab, combining experimental and computational expertise, aiming to address fundamental questions in biology in general and the adaptive immune system in particular. The research activities of our group are divided into two: (1) developing statistical and machine learning-based tools to analyze high-throughput biological data and (2) mining big immunological datasets to extract new insights.

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