Reposted by Troy McDiarmidJay Shendure @jshendure.bsky.social · 31/07/2026Thrilled to post thread re: new single-cell lineage of mouse embryo reconstructed w/ DNA Typewriter. One animal, zygote to late organogenesis (E13.5). Tree has 1,340,794 transcriptionally profiled, annotated tips (cells), 1,142,588 dated internal nodes, rooted at zygote 1/n 313559
Reposted by Troy McDiarmidJohn Doench @johndoench.bsky.social · 06/07/2026New preprint from the group, comparing CRISPRko and CRISPRi via a Perturb-seq readout: www.biorxiv.org/content/10.6...biorxiv.orgDirect comparison of CRISPR knockout and interference with Perturb-seqCRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) are two workhorse technologies for loss-of-function studies, yet direct comparisons between the two are scant relative to their widespread ... 14117
Reposted by Troy McDiarmidDjavad Mowafaghian Centre for Brain Health (DMCBH) @dmcbrainhealth.bsky.social · 18/06/2026Meet @troymcdiarmid.bsky.social, an Assistant Professor in UBC's School of Biomedical Engineering. Dr. McDiarmid is focused on bridging neuroscience and bioengineering to understand brain function. At the core of his work is a powerful idea: what if cells could record their own history?centreforbrainhealth.caFrom blueprint to black box: Dr. Troy McDiarmid is turning DNA into a record of brain health - Djavad Mowafaghian Centre for Brain Health | DMCBHDr. Troy McDiarmid grew up in rural Ontario watching people he loved change in ways nobody could explain. Multiple family members experienced dementia and 091
Troy McDiarmid @troymcdiarmid.bsky.social · 10/04/2026Beautiful work @cxqiu.bsky.social @jshendure.bsky.social and co.! 020
Troy McDiarmid @troymcdiarmid.bsky.social · 02/04/2026@sbmeubc.bsky.social @dmcbrainhealth.bsky.social 000
Troy McDiarmid @troymcdiarmid.bsky.social · 02/04/2026Stoked to announce that I’m starting a lab as an Assistant Professor in the School of Biomedical Engineering and Centre for Brain Health at UBC! mcdiarmid-lab.sbme.ubc.ca Recruiting at all levels - please share the word! Cheers and happy long weekend all! 14116
Reposted by Troy McDiarmidCarl de Boer @carldeboer.bsky.social · 18/03/2026New preprint from our lab where we learn some interesting things about the context specificity of TFs in their regulation of gene expression by dissecting MPRA-trained sequence-expression models. Surprising guest appearance from RNA Pol III(!) Thread from 1st author @sambean12.bsky.social 👇 062
Reposted by Troy McDiarmidNika Shakiba @nikashakiba.bsky.social · 27/02/2026[Plz 📢] A little late to the party, but check out our perspective on how cellular heterogeneity can be your friend😊 or foe😠 in cell therapy manufacturing🧫. Shout out to Yeganeh, Hourieh, Enzo, Ali, Yonatan: www.cell.com/cell-systems... @sbmeubc.bsky.socialcell.comHarnessing heterogeneity for the rational design of cell manufacturingDorri Nokoorani et al. argue that heterogeneity can be harnessed as a design feature in the quality-by-design toolkit to optimize the yield, quality, and robustness of bioprocesses for manufacturing s... 031
Reposted by Troy McDiarmidCarl de Boer @carldeboer.bsky.social · 25/02/2026We wrote a perspective "How to build the regulatory genome: a constructionist guide to the cis-regulatory code", out in Development yesterday. Title says it all. Find it here: journals.biologists.com/dev/article/... 14421
Reposted by Troy McDiarmidWill Chen @chenomics.bsky.social · 13/02/2026We have significantly improved the protocol for recording CRE activities and orders with ENGRAM. We also designed new plasmids for easier cloning. Great work with @jennynathans.bsky.social, @troymcdiarmid.bsky.social and @jshendure.bsky.social . Happy recording!! 095
Troy McDiarmid @troymcdiarmid.bsky.social · 15/02/2026Check out our new protocol paper on molecular recording of transcriptional events in genomic DNA! Super fun pulling this together with @jennynathans.bsky.social @chenomics.bsky.social and @jshendure.bsky.social 034
Reposted by Troy McDiarmidJenny Nathans @jennynathans.bsky.social · 13/02/2026Super happy to share our protocol for ENGRAM is out in Nature Protocols! This was fun to write with @chenomics.bsky.social @troymcdiarmid.bsky.social @jshendure.bsky.social. In it we describe how to record CRE identity, activity, and order in mammalian cells. 0116
Reposted by Troy McDiarmidEmma Dann @emmamarydann.bsky.social · 05/01/2026Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025tinyurl.comGenome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traitsGene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ... 26529
Troy McDiarmid @troymcdiarmid.bsky.social · 12/11/2025We added several additional experiments using the parts to target alternate loci, measure both transcription and editing, and more. Great experience working on this with Megan Taylor , @jshendure.bsky.social and co. and very rewarding to see the rapid uptake by the community. Cheers! 010
Troy McDiarmid @troymcdiarmid.bsky.social · 12/11/2025Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com 12410
Reposted by Troy McDiarmidNick Page @nicholaspage.bsky.social · 06/11/2025🚀 Very excited to share the first major work from my PhD!! We combined MPRA and CRISPRa in excitatory neurons to test and validate cis-regulation therapies for hundreds of haploinsufficient neurodevelopmental disorder genes. 🧬🔬 www.biorxiv.org/content/10.1... 1185
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Thanks to all co-authors on and off bluesky, especially @nadavahituv.bsky.social and @jshendure.bsky.social, as well as the funders and families. Cheers! 000
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Our results provide a comprehensive resource of active, target-linked human neural enhancers for NDD genes and gRNA reagents for CRT development. More broadly, this work establishes a generalizable strategy for discovering CRT gRNA candidates across cell types and haploinsufficient disorders. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Finally, we confirmed that several of the CRISPRa gRNAs identified here demonstrated selective and therapeutically relevant upregulation of SCN2A, CHD8, CTNND2 and TCF4 when delivered virally to patient cell lines, human cerebral organoids, and a humanized mouse model of hTcf4. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025We identified hundreds of promoter- and enhancer-targeting CRISPRa gRNAs that upregulated 200 of the 337 NDD genes in human neurons, including 91 novel enhancer-gene pairs. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Next, we applied multiplex single-cell CRISPRa screening with 15,643 gRNAs to test all MPRA-prioritized cCREs and 761 promoters of NDD genes in their endogenous genomic contexts. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025We then tested all 5,425 candidate neuronal enhancers with MPRA, identifying 2,422 that are active in human neurons. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025We first prioritized 337 haploinsufficient NDD risk genes from 42,320 cases. We then nominated 5,425 candidate enhancers for these 337 genes leveraging multiple datasets characterizing the regulatory landscape of the developing human brain, together with various enhancer-gene mapping strategies. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Here, we combined Massively Parallel Reporter Assays (MPRAs) and a multiplex single cell CRISPRa screen to discover functional human neural enhancers whose CRISPRa targeting yields specific upregulation of NDD risk genes. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025However, scaling this cis-regulatory therapy (CRT) paradigm requires pinpointing which candidate cis-regulatory elements (i.e. promoters and enhancers) are active in human neurons, and which can be targeted with CRISPRa to yield specific and therapeutic levels of target gene upregulation. 100
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Many neurodevelopmental disorders are caused by haploinsufficiency - where functional loss of one gene copy leaves insufficient expression from the other. CRISPR-based gene activation (CRISPRa) has emerged as a promising therapeutic approach for NDD caused by haploinsufficiency. 130
Troy McDiarmid @troymcdiarmid.bsky.social · 05/11/2025Stoked to share our latest work entitled: “Large-scale discovery of neural enhancers for cis-regulation therapies” shorturl.at/H3Qww This is an enormous team effort that I had the honour of spearheading with Nick Page and Florence Chardon. Bluetorial below. 23414
Reposted by Troy McDiarmidcxqiu.bsky.social @cxqiu.bsky.social · 04/11/2025Thrilled to share I’ve started my lab at Dartmouth’s Geisel School of Medicine! We focus on mapping cellular trajectories & TF networks in development and Mendelian disorders, exploring new therapies. Join us—postdocs, grads, and scientists welcome! sites.dartmouth.edu/qiulab/ 21710
Reposted by Troy McDiarmidKevin J. Kircher @kevinjkircher.com · 04/10/2025Sometimes I think about how from 1935-1975ish, Bell Labs produced an insane amount of revolutionary science and technology, including 11 Nobel Prizes, the transistor, UNIX, C, the laser, the solar cell, information theory, etc. The secret? Provide scientists with ample, steady, no-strings funding.sites.stat.columbia.edu 491715482
Reposted by Troy McDiarmidSeth Shipman @seth-shipman.bsky.social · 08/09/2025Check out MitoScribe in our new preprint led by Linhan Wang: www.biorxiv.org/content/10.1... It's an analog molecular recorder that uses neutral base edits to the mitochondrial genome to store information about historical signaling in a cell. Single cell resolution at scale (see next post)! 175
Reposted by Troy McDiarmidAndrew Payne @andrewcpayne.bsky.social · 01/10/2025E11 Bio is excited to unveil PRISM technology for mapping brain wiring with simple light microscopes. Today, brain mapping in humans and other mammals is bottlenecked by accurate neuron tracing. PRISM uses molecular ID codes and AI to help neurons trace themselves. Read more: e11.bio/blog/prism 16030
Reposted by Troy McDiarmidErich M. Schwarz @erichmschwarz.bsky.social · 01/08/2025After 10 years of work, a complete telomere-to-telomere gap-free genome for C. elegans finally exists: it has 106 Mb rather than the textbook 100.3 Mb, and up to 366 additional genes. genome.cshlp.org/content/35/8... 410237
Reposted by Troy McDiarmidMichael Hendricks 🇨🇦 @michaelhendricks.bsky.social · 27/09/2025I'll never get tired of these. (courtesy of Sebasitan Wittekindt doi.org/10.1101/2025...) 1264
Reposted by Troy McDiarmidGlen @vaguebiscuit.bsky.social · 27/09/2025Well don't I feel stupid 283258196758
Reposted by Troy McDiarmidNobu Hamazaki @nobuhamazaki.bsky.social · 26/09/2025New paper from my lab and @jshendure.bsky.social lab! Led by the brilliant @zukailiu.bsky.social and @cxqiu.bsky.social. We tackled how anterior and posterior progenitor cells cooperate to self-organize into an embryonic structure (termed AP-gastruloid). (1/n) www.biorxiv.org/content/10.1... 35420
Reposted by Troy McDiarmidmathiaseder.bsky.social @mathiaseder.bsky.social · 19/09/2025✨Exciting news: the main story of my PhD is out in Science! Together with Christine Moene @cmoene.bsky.social, we explored what happens when you scramble the genome—revealing how Sox2’s position shapes enhancer activation. 📖 Read the full story here: www.science.org/doi/10.1126/...science.orgFunctional maps of a genomic locus reveal confinement of an enhancer by its target geneGenes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt... 39637
Reposted by Troy McDiarmidJesse Engreitz @jengreitz.bsky.social · 19/09/2025New preprint from our lab! What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells? Find out here: www.biorxiv.org/content/10.1... 👇 1/ 16018
Reposted by Troy McDiarmidJohn Ray @jraylab.bsky.social · 18/09/2025Excited to finally present the lab's latest work in defining candidate causal genetic variants that drive autoimmune diseases and their effects on primary human T cell expression and function! www.nature.com/articles/s41...nature.comGenetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks - Nature GeneticsMassively parallel reporter assay in primary human CD4+ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate ... 23819
Reposted by Troy McDiarmidKevin Bender @neurobender.bsky.social · 17/09/2025SCN2A loss is strongly linked to neurodevelopmental delays and, at times, seizure. In an amazing collaboration with @nadavahituv.bsky.social, led by Serena Tamura, Andrew Nelson, and Perry Spratt, we leveraged CRISPR activator approaches to rescue this loss. rdcu.be/eGU0Wrdcu.beCRISPR activation for SCN2A-related neurodevelopmental disordersNature - Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in... 97421
Reposted by Troy McDiarmidJanel Comeau 🍁 @verybadllama.bsky.social · 10/06/2025Google and Meta search both report that Cape Breton Island has its own time zone 12 minutes ahead of mainland Nova Scotia time because they are both drawing that information from a Beaverton article I wrote in 2024 10568031882
Reposted by Troy McDiarmidNozomu Yachie @nzmyachie.bsky.social · 21/05/2025CloneSelect published in Nature Biotechnology @natbiotech.nature.com. This retrospective clone isolation method using CRISPR base editors is a powerful tool in broad biology. A history of Soh in the Yachie lab. www.nature.com/articles/s41...nature.comA multi-kingdom genetic barcoding system for precise clone isolation - Nature BiotechnologyA barcoded CRISPR base editing system isolates target clones from complex mammalian, yeast and bacterial populations. 32913
Troy McDiarmid @troymcdiarmid.bsky.social · 21/05/2025Congrats @nzmyachie.bsky.social and co.! Beautiful work. 110
Reposted by Troy McDiarmidCarl de Boer @carldeboer.bsky.social · 28/04/2025⏰Abstract deadline for the Cascadia Advanced Genomic Technologies Meeting is April 30!⚠️ We're hoping this will be the first of many, catalyzing collaboration and leveraging our regional strength in advanced genomics technologies! See you there! de-boer-lab.github.io/CAGT_meeting/ 034
Reposted by Troy McDiarmidVikram Agarwal @vagar.bsky.social · 13/03/2025Published in today's issue! OPEN ACCESS article, FREE massive dataset, FREE code, FREE pre-trained AI/ML model. #OpenScience was a mountain of work to make this happen: check it out if you haven't already 😉nature.comMassively parallel characterization of transcriptional regulatory elements - NatureLentivirus-based reporter assays for 680,000 regulatory sequences from three cell lines coupled to machine-learning models lead to insights into the grammar of cis-regulatory elements. 0187
Reposted by Troy McDiarmidJeremy Berg @jeremymberg.bsky.social · 22/02/2025I have been trying to find the time to move away from the polical hellscape we find ourselves in to finish and share a bluetorial about science. This helps me remember what this is all about. Ironically, it is about the treatment of pain.media.tenor.comthe word irony is written on a white backgroundALT: the word irony is written on a white background 1033289
Reposted by Troy McDiarmidHarmit Singh Malik @harmitmalik.bsky.social · 23/02/2025I think people both within science and outside science don’t fully appreciate the miracle that were the Covid-19 vaccines. How much courage it took to get the sequence out, how much work had already gone into figuring out the best viral antigen and how best to present it. 1/ 9768188