Shinya Tsukiji

Toward universal binder discovery: Advances in display, computational design and in vivo platforms Protein binders are fundamental tools in chemical biology, key components of biotechnologies, and the foundation of biologics-based medicines. However…

Check out our new review on binder discovery! In a fast-moving world, here are some thoughts we have in the moment.

Congrats @jzy2799.bsky.social and Eddy!!

www.sciencedirect.com/science/arti...

Low-Background Cancer Imaging with a Bioorthogonal Fluorescence Probe and Engineered Reporter Enzyme Bearing a Targeting Moiety Combinatorial use of an antibody–reporter enzyme conjugate and a fluorescence probe activated by the enzyme is a powerful strategy for fluorescence-guided cancer surgery. However, conventional probes ...

Our new paper is out in @jacs.acspublications.org
! We developed a novel pair of bioorthogonal fluorescence probe and engineered reporter enzyme, enabling low-background, bright cancer imaging in vivo. pubs.acs.org/doi/10.1021/...

Efficient Inhibition of TGF-β Signaling via Cytosolic Delivery of a Smad2/3-Binding Peptide Using the Cell-Penetrating PG-Surfactant DKDKC12-K5 to Block Smad2/3 Nuclear Translocation Targeting intracellular signaling molecules that translocate to the nucleus is a promising approach for peptide-based therapeutics. Here, we focused on Smad2/3, key mediators of TGF-β signaling that act as transcription factors upon nuclear entry. To inhibit their nuclear localization, we delivered an Smad2/3-binding SARA peptide into the cytoplasm using our previously developed cell-penetrating carrier, cpPG. A conjugate, SARA-cpPG, was synthesized by linking the SARA peptide to Mal-DKDKC12-K5, a cpPG derivative with an N-terminal maleimide. In A549 cells, SARA-cpPG showed uptake over 20-fold higher than that of the SARA peptide alone and retained cytoplasmic localization. Functionally, SARA-cpPG suppressed TGF-β1-induced actin polymerization and cell migration, comparable to the effects of receptor kinase inhibitor LY2157299. These effects were not observed with cpPG alone or a control conjugate (SARAm-cpPG) containing a nonbinding mutant peptide. Mechanistic studies revealed that SARA-cpPG did not inhibit Smad2/3 phosphorylation but reduced TGF-β target gene expression, suggesting a blockade of nuclear translocation. This suppression was absent in treatments with SARAm-cpPG, cpPG alone, or a non-cytoplasm-specific carrier conjugate (SARA-R8). These findings demonstrate that cpPG enables efficient cytosolic delivery of functional peptides and supports a strategy for intracellular peptide therapeutics targeting nuclear signaling pathways.

New paper from the Mizuno lab (NITech), now out in Bioconjugate Chemistry! Happy to have contributed to this work. Congrats to all the authors! 🥳
@pubs.acs.org
pubs.acs.org/doi/10.1021/...

Super proud of Keita for his excellent presentation at his thesis defense today! He successfully created artificial cells with precisely controlled protein localization, signal transduction, and biosensor functions. Congrats to Dr. Keita Tsutsui (lab PhD #6)! 🥳🎉🎊

PI4P probes: Protocol, paper, and plasmids! Thanks for sharing your tools and expertise @shinyatsukiji.bsky.social 🧬
Get the plasmids here: www.addgene.org/browse/artic...

New paper in @jcb.org! We found a new regulator of p62 phase separation, autophagy, and antioxidant signaling. It is an E3 ligase adaptor called SHKBP1, but the effect is via direct p62 binding, not ubiquitination. Congrats to Lin Luan & team! @weillinstitute.bsky.social

ORP9-PH domain-based fluorescent reporters for visualizing phosphatidylinositol 4-phosphate dynamics in living cells Fluorescent reporters that visualize phosphatidylinositol 4-phosphate (PI4P) in living cells are indispensable to elucidate the roles of this fundamental lipid in cell physiology. However, currently a...

Original paper (M. Ajiki et al.): pubs.rsc.org/en/content/a...
Plasmids encoding the PI4P probes are available from
@addgene.bsky.social: addgene.org/browse/artic...

Spatiotemporal analysis of phosphatidylinositol 4-phosphate dynamics Phosphatidylinositol 4-phosphate (PI4P) is a fundamental phosphoinositide that controls a variety of cellular processes, including signaling, membrane…

Also check out another protocol paper in the same volume of Methods in Enzymology on an ORP9-PH–based PI4P probe, coauthored by Asami Kawasaki and Fubito Nakatsu (Niigata University) and me!
www.sciencedirect.com/science/chap...

Here's the link for 50 days of free access: authors.elsevier.com/a/1mYmWHRzCb...
Original paper (S. Sawada et al.): pubs.acs.org/doi/10.1021/...
Many thanks to @jeremybaskin.bsky.social for the kind invitation!

Palmitoylation-dependent probes for labeling the Golgi apparatus Small-molecule fluorescent probes that selectively stain the Golgi apparatus in living cells are valuable tools for investigating Golgi-associated bio…

Our latest protocol paper on palmitoylation-dependent Golgi probes, coauthored with Shunsuke Sawada (Mukogawa Women’s University) and Keita Tsutsui, is now out in Methods in Enzymology!
www.sciencedirect.com/science/chap...

Today I'd like to honor the memory of my mentor and friend, Roger Tsien, born 1952 February 1. Today would have been Roger's 74th birthday.

Most know Roger for his 2008 Chemistry Nobel Prize with Shimomura and Chalfie. Roger made GFP into the versatile imaging method it is now.

The final version of our new paper is out now - and open access @acs.org Central Science!!

Such a fun collaboration!

pubs.acs.org/doi/10.1021/...

Beautiful work! Congrats to @zyt0329.bsky.social and the team! 🥳
Thanks for using our mDc motif to control the localization of DNA nanodevices—such a clever strategy! 🤩

DNA nanodevices detect an acidic nanolayer on the lysosomal surface - Nature Cell Biology Tan and colleagues develop DNA nanodevices to detect the pH of the lysosomal outer surface, observing an acidic layer generated by TMEM175 that regulates lysosome positioning in response to changes in...

Beyond thrilled to share my PhD work out today in @natcellbio.nature.com , uncovering a nanoscale acidic environment around lysosomes that controls their mobility through proton signaling.🥳🥳🥳

Great thanks to my advisors and excellent peers for helping me！

www.nature.com/articles/s41...

Lead a lab at Janelia Pioneer next-generation tools for biological discovery Apply by Feb. 3, 2026 janelia.org/groupleader

Apply by Feb. 3 to become a Janelia Group Leader!

Group Leaders drive breakthroughs & experimental approaches in imaging, molecular engineering, protein chemistry, mass spectrometry, & methods that don't yet exist. Learn more: janelia.org/groupleader 🧪

Membrane editing with proximity labeling reveals regulators of lipid homeostasis - Nature Chemical Biology Coupling an optogenetic lipid-modifying enzyme with proximity labeling reveals protein networks and mechanisms regulating lipid homeostasis in the membranes of target organelles.

Thrilled to share our latest study, led by @reikatei.bsky.social, in @natchembio.nature.com! We began by asking a simple question—how do cells know if they have too much of a lipid in a particular membrane, and how do they respond to rectify this imbalance?
www.nature.com/articles/s41...
More info 👇

Fast, Bright, and Reversible Fluorescent Labeling of Rhodamine-Binding Proteins Rhodamine dyes conjugated to targeting ligands can yield exceptionally bright fluorescent probes for live-cell imaging. However, the limited permeability of such rhodamine derivatives restricts their ...

A good end to 2025: rhodamine-binders for bioimaging in JACS: pubs.acs.org/doi/10.1021/...

Enjoying science and (occasional) sun at
@pacifichem.bsky.social Thanks to Yoshiyuki Kageyama and Neal Devaraj for organizing the session on "Frontiers in Dynamic Supramolecular Chemistry: Towards Practical Functions".

This work is a great collaboration with Tomoaki Matsuura. Huge thanks to the Bottom-Up Biotech research team for guiding us into the field of cell-free synthetic biology, and congrats to Keita Tsutsui on his very first first-author paper! 🥳

bottomup-biotech.elsi.jp/en/

Eukaryotic-like Synthetic Cells with Chemically Controlled Protein Localization Compartmentalization by organelles and the dynamic control of protein localization within these compartmentalized spaces are key mechanisms for regulating biological processes in eukaryotic cells. Here, we present a bottom-up approach for constructing cell-sized liposomes (giant unilamellar vesicles, GUVs) encapsulating an artificial organelle with chemically controlled protein localization. In this system, proteins fused to Escherichia coli dihydrofolate reductase are rapidly recruited on demand from the inner solution to the interior of a DNA-droplet-based (“nucleus”-like) organelle within GUVs upon addition of a synthetic, DNA-binding trimethoprim derivative to the external solution. By coupling this system with a sequence-specific protease, we constructed a synthetic cell platform that enables chemically induced, multistep cascade reactions─including protein relocalization, organelle-specific enzymatic activity, and product release from the organelle─that culminate in the control of synthetic-cell phenotypes, such as pore formation in the GUV membrane. This work provides a versatile platform for the bottom-up creation of eukaryotic-like synthetic cells with sophisticated and programmable functions.

One more paper from our lab! This ACS Synthetic Biology paper reports bottom-up construction of eukaryotic-like synthetic cells with an artificial nucleus-like organelle, enabling on-demand protein localization control by a small molecule. 💊 pubs.acs.org/doi/full/10....

This work was made possible by a great collaboration with @kjohnsson.bsky.social and @helenfarrants.bsky.social, developers of LAMA, as well as Kazuhiro Aoki! Many thanks to all our collaborators, and congrats to Yoko Fukaya on her memorable first-author paper! 🥳

A Chemically Switchable Synthetic Condensate Platform for Reversible Protein Sequestration and Release Creating artificial organelles that sequester and release specific proteins in response to a small molecule in mammalian cells is an attractive approach for regulating protein function. In this work, ...

Our latest paper on a novel synthetic condensate platform, LAMA-SPREC, is out in ACS Chemical Biology! It enables chemically switchable and reversible control of protein function via sequestration and release in mammalian cells. 🔬💊🚿
pubs.acs.org/doi/full/10....

Lipid-Mediated Sequential Recruitment of Proteins Via Dual SLIPT and Dual SLIPTNVOC in Live Cells Cellular phenomena such as signal integration and transmission are based on the correct spatiotemporal organization of biomolecules within the cell. Therefore, the targeted manipul...

An excellent new protocol from Kristina Bayer and Richard Wombacher (@wombacherlab.bsky.social)! Their lipid-mediated dual SLIPT and dual SLIPT(NVOC) system offers powerful sequential control of protein recruitment in live cells. 🔬💊🔦
bio-protocol.org/en/bpdetail?...

We really enjoyed the Post-BB2025 Mini-Symposium! All the talks were very stimulating, and we got to hear many exciting unpublished results. Huge thanks to Neal and all the invited speakers for making this symposium a success! 🥳

Excellent review on induced proximity-based therapeutic modalities! Thank you, @dannomura.bsky.social, for featuring our work in the "Targeted Protein Subcellular Localization" section and in Fig. 8!

Induced proximity-based therapeutic modalities - Nature Reviews Drug Discovery Induced proximity modalities encompass monovalent and bifunctional agents, such as molecular glues and proteolysis-targeting chimeras, that induce an interaction between biomolecules to functionally m...

Induced proximity-based therapeutic modalities
nature.com/articles/s41...
rdcu.be/eOfBH

This new Review by @dannomura.bsky.social et al. discusses the rapidly expanding landscape of therapeutic approaches based on inducing proximity between proteins, including targeted protein degraders and more

Here is the program. If you are nearby and interested, please feel free to join us! 😃

📣 We will organize the “Post-BB2025 Mini-Symposium on Lipid-Focused Chemical and Synthetic Biology” on Nov 27 at NITech!
Speakers: Prof. Neal K. Devaraj, Prof. Shohei Uchinomiya, Prof. Hao Zhu, Prof. Sayuri Higashi, Dr. Kristina V. Bayer, and Prof. Satoshi Yamaguchi.

Open Positions - SCHOOL OF SCIENCE THE UNIVERSITY OF TOKYO This is the open recruitment information for School of Science, the University of Tokyo.

🧪 The Campbell lab at UTokyo is looking to hire a postdoctoral researcher for a project focused on protein engineering for optogenetic tool development. Details here: www.s.u-tokyo.ac.jp/en/recruit/?...

UZH: PhD Position in Redox Chemical Biology We are a dynamic, interdisciplinary, medium-size lab working at the interface of chemistry and biology. We work on the development of probes to visualize and control biological processes in living sys...

We are hiring! Excited about redox chemical biology? Help us discover what controls the redox state of the Golgi apparatus. Also, please help us spread the word by reposting this ad. Apply here: jobs.uzh.ch/job-vacancie...