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Our mission is to identify and address fundamental problems in cell biology in this time and age when science and technology are rapidly advancing. We do this by looking at cells using high-resolution microscopy with a passion for new discoveries. In addition, we are committed to empowering the next generation of scientists to cultivate original ideas and create groundbreaking inventions.
Eukaryotic cells contain many different organelles which enable them to compartmentalise biochemical and biological processes. The inter-organelle communication is tightly controlled to respond to environmental cues and coordinate homeostasis. A key organelle for the inter-organelle communication is the endoplasmic reticulum (ER), which is the site of lipid and membrane protein synthesis. The ER is directly connected to the nucleus by junctions with the outer nuclear membrane. This ER-to-nucleus connectivity is crucial for supplying the lipids and proteins that are synthesized in the ER to the nucleus. However, the biogenesis, architecture and maintenance of the ER-nucleus connection have remained elusive.
The correlative live imaging with high resolution electron microscopy that we have established previously, allows to visualise intra-cellular structures in situ in human cells in a spatio-temporally-resolved and quantitative manner. By combining this correlative imaging technology with quantitative live cell imaging and a microscopy-based loss-of-function screens, we will elucidate systematically how the structure and function of the ER-nucleus connection changes during nuclear growth, identify molecular players regulating them, and reveal how the ER-nucleus connectivity mechanistically controls the ER-to-nucleus communication.
Shotaro was born in Tokyo, Japan. He obtained a PhD in Biophysics at Kyoto University. In 2011, he moved to Germany to carry out postdoctoral work at the European Molecular Biology Laboratory (EMBL). In 2019, he started his own lab at the Max Perutz Labs in Vienna.
Using correlative live imaging with high resolution electron microscopy, we revealed that ER-nucleus junctions form narrow hourglass-shaped structures (~15 nm in diameter) which are distinct from the junctions within the ER, and that the junctions start to become specialized in early telophase. This observation strongly suggests that a novel mechanism, distinct from that known to remodel the ER, likely regulates ER-nucleus junctions, and lays the groundwork for many exciting future mechanistic and functional studies, shedding light on gene expression, nuclear organisation, and disease mechanisms.
A correlative live imaging with electron microscopy was established that allows to examine subcellular structures and protein complexes at nano-meter resolution at specific stages of cell-cycle in a quantitative manner, and therefore can enable to visualize biological processes which have not been able to study due to the limited resolution of conventional microscopy.
The correlative imaging technique was applied to study nuclear envelope (NE) assembly during mitotic exit, and could demonstrate for the first time that the NE forms from highly fenestrated ER sheet whose holes progressively shrink. This finding provides a new approach to explore the ER-NE connectivity and ask how it is regulated to ensure proper ER-nucleus communication.
The endoplasmic reticulum connects to the nucleus by constricted junctions that mature after mitosis.
Bragulat-Teixidor Helena, Ishihara Keisuke, Szücs Gréta Martina, Otsuka Shotaro
A quantitative map of nuclear pore assembly reveals two distinct mechanisms.
Otsuka Shotaro, Tempkin Jeremy O B, Zhang Wanlu, Politi Antonio Z, Rybina Arina, Hossain M Julius, Kueblbeck Moritz, Callegari Andrea, Koch Birgit, Morero Natalia Rosalia, Sali Andrej, Ellenberg Jan
A mitotic chromatin phase transition prevents perforation by microtubules.
Schneider Maximilian W G, Gibson Bryan A, Otsuka Shotaro, Spicer Maximilian F D, Petrovic Mina, Blaukopf Claudia, Langer Christoph C H, Batty Paul, Nagaraju Thejaswi, Doolittle Lynda K, Rosen Michael K, Gerlich Daniel W
Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane openings.
Otsuka Shotaro, Steyer Anna M, Schorb Martin, Hériché Jean-Karim, Hossain M Julius, Sethi Suruchi, Kueblbeck Moritz, Schwab Yannick, Beck Martin, Ellenberg Jan
Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope.
Otsuka Shotaro, Bui Khanh Huy, Schorb Martin, Hossain M Julius, Politi Antonio Z, Koch Birgit, Eltsov Mikhail, Beck Martin, Ellenberg Jan
2024-2029.
2021-2025. The Otsuka Group participates in the special doctoral program 'Signaling Mechanisms in Cellular Homeostasis (SMICH)', funded by the Austrian Science Fund (FWF).
2023-2024. Project title: “How do endoplasmic reticulum and nucleus communicate?" (P 36743-B).
2020-2024. A collaboration project with Daniel Gerlich's group at IMBA.
Project title: “Elucidating the mechanics of mitotic chromosome assembly by light-, electron-, and atomic force microscopy"
Austrian Academy of Sciences DOC Fellowship: Helena Bragulat Teixidor