Deen Sun

Our biorxiv preprint is now online @nchembio 🎉 rdcu.be/evDDq We made substantial revisions and added new experiments. Thanks to everyone who made this possible. Our journey continues!

🚨Excited to share this collaborative work with Ming-Ming. Check it out!🎉▶️biorxiv.org/content/10.648…

Our November issue is live! nature.com/nchembio/volum… The cover depicts a SEM image of a dorsal surface of liverwort M. polymorpha female thallus. Liverwort were found to have a noncanonical pathway for the regulation of master growth repressor DELLA.

Our RAEFISH spatial transcriptomics technology is now published in Cell @CellCellPress! RAEFISH enables sequencing-free whole genome spatial transcriptomics at single molecule resolution. This work represents the first time that transcripts from more than 23,000 genes were directly probed and imaged in situ with any technology, and the first time numerous different gRNAs were directly probed and distinguished by imaging in a high-content CRISPR screen. The challenge: Recent breakthroughs in spatial transcriptomic technologies, from us and others, have greatly improved our ability to profile cell types, states, cellular interactions, and the underlying gene programs within the native tissue contexts. However, these technologies have limitations. Methods based on 2D-array-capture/tagging and ex situ sequencing offer genome-scale coverage, but lack the resolution needed to accurately study fine spatial organization. In contrast, image-based methods that rely on highly multiplexed fluorescence in situ hybridization or in situ sequencing provide single-molecule resolution and resolve fine spatial organization, but require pre-selecting a limited set of target genes (typically hundreds to a few thousand genes), which limits discovery and sometimes leads to only validations of prior knowledge due to the pre-selected targets being well studied in the context. The solution: RAEFISH, our lab's new flagship image-based spatial transcriptomics technology, simultaneously enables single-molecule spatial resolution and whole-genome level coverage of long and short, endogenous and engineered RNA species in cell cultures and intact tissues. The results: 🔥 We performed RAEFISH targeting 23,312 human genes in cell cultures, and demonstrated hypothesis-free discovery of cell cycle associated genes and subcellular localization patterns of transcripts, including nearly the entire protein coding transcriptome and additional long noncoding RNAs. 🔥 We performed RAEFISH targeting 21,955 mouse genes in mouse liver, placenta, and lymph node tissues. Our analyses on immediately neighboring cells uncovered intriguing cell-cell interactions and previously unknown gene expression programs underlying the interactions, such as those between cholangiocytes and immune cells. 🔥 Finally, we further developed RAEFISH to directly read out guide RNAs (gRNAs), demonstrating Perturb-RAEFISH in an image-based high-content CRISPR screen. The capacity of Perturb-RAEFISH to directly read out gRNAs addresses a crucial limitation of previous techniques that read out a barcode/identifier sequence paired with each gRNA species, as the pairing can be shuffled due to RNA recombination intrinsic to lentivirus used in such screens, which limits screen sensitivity and accuracy. In summary, RAEFISH provides the biomedical research community with a generalizable research tool, which will bring more spatial and mechanistic insights across health and disease. This work was co-led by my postdocs Drs. @ChengYubao, Shengyuan Dang, and Yuan Zhang, and was supported by the @NIH, @genome_gov, @sennetresearch, and @psscra. I would like to thank our co-authors, funding agencies, editor, reviewers, and my whole lab @YaleGenetics @YaleCellBio @YaleCancer @YaleMed @Yale. Link to paper: cell.com/cell/fulltext/…

Molecular recording of cellular protein kinase activity with chemical labeling: nature.com/articles/s4158…

🚨 New preprint alert! Looking for a peptide tag alternative to the classic HaloTag for protein labeling? Check out our latest work "A high-affinity split-HaloTag for live-cell protein labeling" on #bioRxiv 🔗biorxiv.org/content/10.110…

Looking for a fluorescent biosensor and don’t know where to start? Want a comprehensive overview of the field? Check out our new review in @ACSChemRev online now as an ASAP article! From co-first authors @AMMGest @AyseZSahan @yanghao_zhong doi.org/10.1021/acs.ch…

@TianyanL Thank you Tianyan!

@DeenSun3 Congrats 🎉

🚨Excited to share my latest postdoc work in this #biorxiv preprint on developing split-HaloTag recorders for capturing cellular transient kinase activity, Kinprola (kinase activity dependent protein labeling). biorxiv.org/content/10.110… 🧵 (1/7)

Thanks especially to Kai Johnsson and to all involved! On X you will find @DirkCHoffmann @KimBoonekamp @Winkler_Lab @wick_wolfgang @Michael_Boutros @yulonglilab @mpi_mr_hd @EPFL_en @uniklinik_hd @UniHeidelberg @PKU1898 @AvHStiftung @ResearchLifesci (7/7)

Kinprola enables the recording of PKA activation in primary neurons, acute brain slices upon drug or electrical stimulation, and for the tracking of drug-induced neuromodulation in freely moving mice🐭. (6/7)

An inspiring read! Synthesis at the Interface of Chemistry and Biology | Accounts of Chemical Research pubs.acs.org/doi/10.1021/ac…

Glad to contribute to this work led by my phd lab @XingChen_PKU Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients | Journal of the American Chemical Society pubs.acs.org/doi/10.1021/ja…

🔬Join us at #ChemoRevolution, where chemistry meets biology to reshape our understanding of life! Explore cutting-edge tools and groundbreaking discoveries in chemical biology. Connect with global experts and rising stars in the field. Be part of the scientific revolution!

a very nice outlook

Our new #MPIMRSpotlight features @DeenSun3, postdoctoral researcher in the Chemical Biology department! ⚗️Check out what he has to say about his work at the Institute and interest in spying on brains!🔎🧠 👀