Jonathan S. Weissman's lab at the @WhiteheadInst/@MIT. Account run by lab members.
Cambridge, MA
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Gene expression levels are continuous rather than binary. To access biological phenotypes along such a continuum, we developed a method to titrate gene expression using systematically attenuated CRISPR guide RNAs. Check out our work in @NatureBiotech
Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs go.nature.com/35QGI6f
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Perturb-seq is a powerful tool for understanding genes and genetic networks at the single-cell level. We developed a method for large-scale Perturb-seq screens with flexible guide designs and targeted sequencing. Check out our work in @NatureBiotech: nature.com/articles/s41587-0…
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Have you ever wondered exactly what happens when Cas9 creates a double-strand break? We're excited to share Repair-seq, an approach for screening how thousands of genetic perturbations change the mutations that cells make when they repair DNA damage. biorxiv.org/content/10.1101/…
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Out now in @CellCellPress, we report the development of Repair-seq, a high-throughput screening approach for systematically mapping DNA repair pathways. cell.com/cell/fulltext/S0092…
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We are so excited to share the latest from the lab (joint with @YosefLab and @LabJacks ), where we engineer an evolving CRISPR-based, single-cell lineage tracer into a mouse model of lung cancer and monitor tumor growth and evolution with unprecedented resolution.
We're ecstatic to present our manuscript on recording the evolutionary dynamics in a mouse model of lung cancer with an evolving lineage tracer. Congrats to @dianyang1117 for co-leading and @JswLab @YosefLab @LabJacks for this joint effort. Biorxiv link: tinyurl.com/f43de4nw
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Check out our latest pre-print describing a strategy for CRISPR screens in human DCs and its use to probe how DCs recognize immune ligands (LPSs) from the microbome: biorxiv.org/content/10.1101/…
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Check out our latest paper in @NatureBiotech on functional single-cell genomics of HCMV infection! @marcoyannic used Perturb-seq to study how the course of infection changes when we target host factors or critical viral genes.
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Past events in cancer progression, like metastasis, leave clear signatures in cancer cells' ancestry. Using our CRISPR-based single-cell lineage tracer, we explored the rates, routes, and patterns of metastatic spread in a lung cancer mouse model. Check out our new preprint 👇
Continuous lineage recording reveals rapid, multidirectional metastasis in a lung cancer xenograft model in mouse biorxiv.org/cgi/content/shor… #bioRxiv
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We are currently hiring technicians through HHMI & the Whitehead Institute! Please encourage motivated undergrads to apply!
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Excited to announce the pre-print (biorxiv.org/content/10.1101/…) for our work studying the biogenesis pathways of mitochondrial outer membrane alpha-helical proteins! A really fun collaboration with the (@voorheeslab). Follow this 🧵 for a sneak peak (1/12)
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Out now on biorxiv, check out our genome-scale Perturb-seq manuscript! Check out this thread from @josephmreplogle for more details
I'm thrilled to share our latest work performing genome-scale Perturb-seq screens to explore a remarkable breadth of questions in genetics and cell biology (thread below). Congrats to Reuben Saunders, Tom Norman, and @JSWlab for co-leading this work. biorxiv.org/content/10.1101/…
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In collaboration with @weallen1 and Xiaowei Zhuang, we have developed Perturb-multi: biorxiv.org/content/10.1101/…
In collaboration with Reuben Saunders, @JswLab, and Xiaowei Zhuang, we are very excited to release Perturb-Multi: a platform for pooled multimodal genetic screens in intact mammalian tissue.
Check it out!
biorxiv.org/content/10.1101/…
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Glad to have our work using natural barcode-based lineage tracing to decipher cell states and genealogies of human hematopoiesis out today in @Nature, led by @chenweng1991, a great collaboration with @bloodgenes. doi.org/10.1038/s41586-024-0…
Check out this terrific thread as well!
Very delighted to share our work Deciphering cell states and genealogies of human hematopoiesis online today in @Nature (Accelerated Preview version). It is a really great collaboration of Weissman lab @JswLab and Sankaran lab @bloodgenes doi.org/10.1038/s41586-024-0… 🧵(1/n)
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We are looking for a motivated recent grad to join us as a lab technician! Perfect opportunity to gain more research experience for 2-3 years before applying to MD and/or PhD programs. Follow the link below to apply:
👉 tinyurl.com/WeissmanLabTech
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Ribosome stalling leads to selective translation inhibition. Genome-scale CRISPRi screens uncovered that the translation inhibitors GIGYF2 and 4EHP coordinate with RQC to maintain proteostasis. Check out our work in @MolecularCell
Online Now: GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control dlvr.it/RcXHYC
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One key component of Perturb-Multi is in vivo Perturb-seq of formaldehyde-fixed tissue, enabled by the Flex reagents from @10xGenomics.
In collaboration with Reuben Saunders, @JswLab, and Xiaowei Zhuang, we are very excited to release Perturb-Multi: a platform for pooled multimodal genetic screens in intact mammalian tissue.
Check it out!
biorxiv.org/content/10.1101/…
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Find an interactive browser with data from our genome-scale Perturb-seq paper (doi.org/10.1016/j.cell.2022.…) designed by @alexlenail at: gwps.wi.mit.edu/
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Our wonderful collaborators on the Perturb-Multi work (biorxiv.org/content/10.1101/…) are now here and on the other app, at @ZhuangLab
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Check out opencell.czbiohub.org and the accompanying preprints!
Terrific work spearheaded by @LeonettiManuel and team, combining genome engineering, interaction proteomics, and confocal imaging. Happy to be a part of this collaboration with @czbiohub @loicaroyer @labs_mann
Endogenous tagging + 3D live-cell imaging + mass-spec interactome = opencell.czbiohub.org, an open-source map of the human proteome. So excited for our first release, wonderful collaboration with @labs_mann @loicaroyer & many other colleagues. @OpenCellCZB
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The Center for Genome Editing and Recording (cger.bio/) is doing some exciting education/outreach work. We are now offering a training workshop to help college-level instructors from Historically Black Colleges and Universities (1/3)
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Exciting work from the lab led by @JingchuanLuo with coauthors @KhandwalaStuti @LevineZebulon and JJ Hu
I'm thrilled to share our work from @JswLab (sciencedirect.com/science/ar…). We developed LOCL-TL, an optogenetic approach for monitoring localized translation in mammalian cells. LOCL-TL revealed two mechanistically distinct strategies for mitochondrially localized translation.
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Congratulations to James Numez and collaborators for their RENDER platform for delivering epigenetic editors using engineered VLPs. RENDER broadly advances our ability to deliver epigenome editors into human cells and will likely find ciritcal uses both in fundamental and therapeutic applications.
biorxiv.org/content/10.1101/…
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Check out our new preprint identifying MTCH2 as an mitochondrial outer membrane protein insertase in mammalian cells! Great collaboration with @voorheeslab @WhiteheadInst @Caltech
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We are looking for a motivated recent grad (or soon-to-be grad) to join us as a lab technician! A great opportunity to gain research experience for 2-3 years before applying to MD and/or PhD programs. Apply here: shorturl.at/qruFU
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Crowdsourcing a functional genomics/virology question being debated in the lab: when a single pseudodiploid lentiviral particle enters a cell, what limits the number of typical proviral integrations to 1?
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Excited to share the lab's collaboration with @NadigAjay
@josephmreplogle and @Luke0connor: an expanding atlas of Perturb-seq datasets across multiple cell types
Check out our latest large-scale Perturb-seq on biorxiv! biorxiv.org/content/10.1101/…
A new stat gen/GWAS-inspired analytic framework + large-scale screens in an expanded range of cell types
Thanks @NadigAjay and @Luke0connor for involving us!
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A very clever strategy for making "variant-proof" therapeutic antibodies - biorxiv.org/content/10.1101/…
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Exciting work from the lab, on the mechanism of OSK rejuvenation, led by @Y_Ryan_Lu with lab co-authors James Cameron, @MohamedBrolosy, @AniaPuszynska, @Xiaojie_Qiu.
1/ Can we find more precise and even safer ways to rejuvenate vision?
As a step towards this goal, I am excited to share this preprint of my 1st postdoc work from @JswLab with amazing collaborators, esp. @Bruce_Ksander! Using functional genomics, we discovered GSTA4 as a key OSK effector for oxidative resilience—overexpressing it alone rejuvenates RPE & restores vision.
A breakdown👇biorxiv.org/content/10.1101/…
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#RNAVelocity reveals the local fate of cell states. Our Dynamo framework extends this to learn the global dynamics of cell fate transitions, augmented by single-cell metabolic labeling experiments.
Check out some of Dynamo’s latest exciting updates:
Finally! We now provide detailed Dynamo tutorials for two metabolic labeling datasets and six other "conventional" scRNA-seq datasets. Check those beautiful velocity field plots and learn more about the tutorials and get the newest Dynamo here: github.com/aristoteleo/dynam…
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Will is developing the world's best tools to dissect the cellular and tissue homeostasis. Don't miss this incredible opportunity to join him and inaugurate a new era of integrative physiology.
Very excited to announce that I'll be starting a laboratory studying the biology of homeostasis as an assistant professor in the Department of Developmental Biology (@DevBioStanford) at @Stanford in July!
allenlabstanford.org
ALT http://www.allenlabstanford.org
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On behalf of the amazing team in @JswLab, we’re excited to share PEtracer (biorxiv.org/content/10.1101/…) a prime editing-based evolving lineage recorder compatible with both scRNA-seq and high-resolution imaging readouts in intact tissue. By applying PEtracer in a syngeneic mouse model of lung metastasis, we dissect how cell-intrinsic and environmental factors coordinately shape tumor evolution in vivo.
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See the lab's data collaborating with @UltimaGenomics in the thread below
$1/Gb? I had a great experience collaborating w/ Ultima genomics to sequence genome-scale Perturb-seq libraries on their new open fluidics sequencing platform: biorxiv.org/content/10.1101/… (see Figure S13 for comparison)
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A close collaboration with @mfgrp at Stanford, led jointly by post-docs Marco Jost (off to start a lab at HMS shortly) and @alifescientist, and with key contributions from @jeff_hussmann in the lab and Giana Cirolia at the Biohub
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This work arose from a fantastic collaboration with @bsadamson and @10xGenomics, all motivated by doing big Perturb-seq experiments with broad applications.
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The data quality from fixed-cell Perturb-seq is at least as high as that we have seen with RT-based scRNA-seq, and the economics are significantly improved due to the droplet overloading enabled by the probe barcodes from @10xGenomics.
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We used lentiviral delivery of sgRNAs to create genetic mosaic organs, separately knocking out hundreds of genes in the liver of a single mouse.
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Congrats @NadigAjay and @Luke0connor!
Congrats @NadigAjay on TRADE out now in @NatureGenet: nature.com/articles/s41588-0…
These statistical metrics enable more meaningful comparisons in Perturb-seq atlases.
Also, now find the HepG2 and Jurkat Perturb-seq datasets on GEO GSE264667!
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Tweetorial with the main findings:
🚨🦠🧵Fresh #herpesvirus content:
1/ We posted an updated preprint of our #singlecell functional genomics study of human #cytomegalovirus infection.
I didn't do a tweetorial with the initial version, so here it comes now 👇
biorxiv.org/content/10.1101/…
#lovevirology #herpes4life
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Our data provides a new look into the cytosolic chaperoning and targeting mechanisms for mammalian OMM proteins, and a complete picture of the diverse biogenesis pathways required for the full range of substrates (11/12)
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We hope that our fixed-cell methods will enable a new era of large-scale in vivo Perturb-seq!
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Congrats, Mohamed!
How do cellular robustness machineries⚙️ influence the landscape of genetic disease? Grantee @MohamedBrolosy investigates how transcriptional adaptation is triggered. 🎉Congrats Dr. El-Brolosy! @Harvard @WhiteheadInst
🙏 #HFScout @MireilleKamariz
@UCLA
hypothesisfund.org/portfolio
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Our fixed-cell Perturb-multi methods enable scRNA-seq and multiplexed imaging on alternate slices from the same genetic mosaic mouse tissues.
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See this thread for more details! nitter.app/jeff_hussmann/status/1…
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Perturb-Multi generates rich, multimodal data that can generate fundamentally new insights about the impact of genetic perturbations on tissue function. Check it out!
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You can find the preprint here: biorxiv.org/content/10.1101/…
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We then hybridize the fixed cells to custom split probes that directly bind to our sgRNAs, alongside the transcriptome-wide mRNA libraries from @10xGenomics.
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Fixed-cell Perturb-seq is much easier and less stressful than live cell Perturb-seq—both for the user and for the cells! We love working with samples that can sit in the fridge for days with minimal degradation.
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See this thread from @bsadamson for more details.
Our work developing Repair-seq, a platform for studying #DNArepair processes, and its application to double-strand breaks is out today @CellCellPress. Alongside, we release seq.repair, a portal for exploring many, many DNA repair phenotypes! cell.com/cell/fulltext/S0092…
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master the basics of teaching CRISPR-based genome editing. The workshop will consist of 4-5, one-hour lectures from experts in the field, including prominent scientists like Jonathan Weissman. (2/3)
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Perturb-Multi is a platform for pooled genetic screens in intact mammalian tissue with spatial (MERFISH and multiplexed immunofluorescence) and scRNA-seq-based phenotyping.
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Thanks to everyone involved @voorheeslab, @guna_alina, @tstevens5000, @aj_inglis, @WhiteheadInst, @caltech and to you for reading! #mitochondria #membrane (12/12)
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A preliminary version of this paper is available on @biorxivpreprint: biorxiv.org/content/10.1101/…
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This work was spearheaded by Jeff Quinn and @mattjonesucsf, and a collaboration with Nir Yosef @YosefLab and Trever Bivona's lab.
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We harvest mosaic mouse tissues by perfusion with formaldehyde, which immediately locks transcriptional phenotypes in place and protects RNA. We then dissociate the fixed tissue and use FACS to select perturbed cells.
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The workshop will also include and five days of hands-on learning in an MIT lab. We are happy to share that applications are now open! Apply here: app.smartsheet.com/b/form/73… (3/3)
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Also, check out our recent paper on Cassiopeia, our computational framework for analyzing lineage tracing data 👇
I'm ecstatic to introduce the published form of our joint effort between @JswLab and @YosefLab characterizing Cassiopeia, our tool for inferring phylogenies from CRISPR/Cas9-enabled lineage tracing data! See our manuscript now published in @GenomeBiology: bit.ly/2RGJA17
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A team effort led by Marco Jost and Dan Santos as well as a fantastic collaboration with the group of Carol Gross
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Here's a link to the biorXiv version: biorxiv.org/content/10.1101/…
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Using genome-wide CRISPRi screens with topologically distinct alpha-helical OMM substrates, we identified several factors differentially regulating biogenesis, including the co-translational chaperone NAC, putative cytosolic chaperone TTC1, and OMM E3 ligase MARCHF5 (3/12)
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This project was spearheaded by @Kelsey_Hickey22 and @kkostova1 and a collaboration with @GreenLabJHMI.
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