2023 ANNUAL REPORT | BAR-ILAN INSTITUTE

87 the dynamics of signaling pathways as they converge at the promoter and activate transcription, quantified the dynamic travels of mRNPs from the gene throughout the nucleoplasm and export through the NPC, and examined the fate of mRNA in the cytoplasm in P bodies and stress granules. We use live-cell measurements performed on fluorescence microscopes and include quantifications of the measured processes using singlemolecule analysis and mathematical modeling. RNA accumulates in stress granules formed in cancerous patient-derived lung organoids under arsenite treatment. RNAcyan, SGs-magenta. Cell outline- green. Publications 2022 and 2023 • Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor,Anders S Hansen, Bo Huang, Danwei Huangfu,Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-DeCastillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong. “Spatial and temporal organization of the genome: Current state and future aims of the 4D nucleome project”. Molecular Cell, 2023. • Roi Isaac, Yaron Vinik, Martin Mikl, Shani Nadav-Eliyahu, Hadas Shatz-Azoulay, Adi Yaakobi, Natalie DeForest, Amit R Majithia, Nicholas JG Webster, Yaron Shav-Tal, Eytan Elhanany, Yehiel Zick. “A seven-transmembrane protein-TM7SF3, resides in nuclear speckles and regulates alternative splicing”. iScience, 2023. • Asaf Ashkenazy-Titelman, Mohammad Khaled Atrash, Alon Boocholez, Noa Kinor, Yaron Shav-Tal. “RNA export through the nuclear pore complex is directional”. Nature Communications, 2022. • Sarah E Hasenson, Ella Alkalay, Mohammad K Atrash, Alon Boocholez, Julianna Gershbaum, Hodaya HochbergLaufer, Yaron Shav-Tal. “The association of MEG3 lncRNA with nuclear speckles in living cells”. Cells, 2022. • Avital Schwed-Gross, Hila Hamiel, Gabriel P Faber, Mor Angel, Rakefet Ben-Yishay, Jennifer IC Benichou, Dana Ishay-Ronen, Yaron Shav-Tal. “Glucocorticoids enhance chemotherapy-driven stress granule assembly and impair granule dynamics, leading to cell death”. Journal of Cell Science, 2022. • Gabriel P Faber, Shani Nadav-Eliyahu, Yaron Shav-Tal. “Nuclear speckles–a driving force in gene expression”. Journal of Cell Science, 2022. • Luna Tammer, Ofir Hameiri, Ifat Keydar, Vanessa Rachel Roy, Asaf AshkenazyTitelman, Noélia Custódio, Itay Sason, Ronna Shayevitch, Victoria RodríguezVaello, José Rino, Galit Lev Maor, Yodfat Leader, Doha Khair, Erez Lieberman Aiden, Ran Elkon, Manuel Irimia, Roded Sharan, Yaron Shav-Tal, Maria Carmo-Fonseca, Gil Ast. “Gene architecture directs splicing outcome in separate nuclear spatial regions”. Molecular Cell, 2022. • Noa Dahan, Yury S Bykov, Elizabeth A Boydston, Amir Fadel, Zohar Gazi, Hodaya Hochberg-Laufer, James Martenson, Vlad Denic, Yaron Shav-Tal, Jonathan S Weissman, Naama Aviram, Einat Zalckvar, Maya Schuldiner. “Peroxisome function relies on organelle-associated mRNA translation”. Science Advances, 2022. Prof. Shefi Orit Faculty of Engineering Member of BINA Nano-Biomedicine Center Nano-Bioconvergence Center Research Areas • Neurobiological systems development: image processing and network analysis • Tissue Engineering: Developing skin grafts that enable reinnervation and regeneration • Developing devices for reagents delivery into live tissue at a microscopic resolution • Neuroprosthetic devices: Neuron-Chip interface Abstract Neuro-engineering and Regeneration Our research aims to unveil the basic mechanisms underlying neuronal development and leverages this knowledge towards obtaining improved methods for manipulating and promoting neuronal regeneration. Neurons develop into a wide-variety of shapes with important implications for neuronal function and connectivity. Following nerve injuries, the process of spontaneous nerve regeneration is incomplete. Our approach is multidisciplinary and merges engineering, biology, nanotechnology and material sciences, at the micro and nano scale. We analyze neuronal responses by implementing morphometric measurements, electrophysiological protocols, simulations and bioinformatics. Moreover, in order to target the nervous system and key injured, diseased tissue, we develop drug-delivery technologies, i.e. novel carriers and biolistic setups. (A) In order to study the mechanisms involved in the interactions between neurons and topographically-structured substrates, we fabricate 2D cues at the nanometric scale by photolithography patterning, similar to the scale of cytoskeletal elements in cells. A key process in neuronal guidance is the ability of the sensory-motile growth cones at the tips of growing processes to measure environmental cues and use them for growth. (B) We develop 3D platforms for regeneration 3D hydrogels. We mimic the natural environment of neurons. By controlling the external and internal

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