Troy McDiarmid
@troymcdiarmid.bsky.social
Assistant Professor, School of Biomedical Engineering & Centre for Brain Health University of British Columbia @sbmeubc.bsky.social @dmcbrainhealth.bsky.social https://mcdiarmid-lab.sbme.ubc.ca/
Thrilled 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
New preprint from the group, comparing CRISPRko and CRISPRi via a Perturb-seq readout: www.biorxiv.org/content/10.6...
Direct comparison of CRISPR knockout and interference with Perturb-seq
CRISPR 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 ...
biorxiv.org
Meet @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?
From blueprint to black box: Dr. Troy McDiarmid is turning DNA into a record of brain health - Djavad Mowafaghian Centre for Brain Health | DMCBH
Dr. Troy McDiarmid grew up in rural Ontario watching people he loved change in ways nobody could explain. Multiple family members experienced dementia and
centreforbrainhealth.ca
Beautiful work @cxqiu.bsky.social @jshendure.bsky.social and co.!
cxqiu.bsky.social@cxqiu.bsky.social · 4mo agoNew preprint @cxqiu.bsky.social @jshendure.bsky.social ! Can we learn regulatory grammars of human cell types — by training on mouse development and transferring across 241 mammalian genomes? Introducing STEAM & a whole-organism scATAC-seq atlas from E10 to birth. www.biorxiv.org/content/10.6...
Stoked 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!
New 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 👇
Sambina Islam Aninta@sambean12.bsky.social · 5mo agoMPRAs are the gold-standard tool for measuring how DNA sequences drive gene expression and prioritizing variant effects. In this preprint we asked: does it matter WHERE you place a variant in an MPRA? Spoiler: yes, and it might lead you to miss disease-causing variants. 1/6 doi.org/10.64898/202...
[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.social
Harnessing heterogeneity for the rational design of cell manufacturing
Dorri 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...
cell.com
We 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/...
We 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!!
Jenny Nathans@jennynathans.bsky.social · 6mo agoSuper 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.
Check 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
Nature Protocols@natprot.nature.com · 6mo agoNew Article! Multichannel genomic recording of biological information with ENGRAM
Super 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.
Nature Protocols@natprot.nature.com · 6mo agoNew Article! Multichannel genomic recording of biological information with ENGRAM
Together 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/gwt2025
Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits
Gene 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, ...
tinyurl.com
Our work developing a parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording is now out @natbiotech.nature.com
Nature Biotechnology@natbiotech.nature.com · 9mo agoA parts list of promoters and gRNA scaffolds for mammalian genome engineering and molecular recording - @jshendure.bsky.social @troymcdiarmid.bsky.social @uwgenome.bsky.social go.nature.com/49eTPCu
🚀 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...
Stoked 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.
Thrilled 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/
Sometimes 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
Check 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)!
E11 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
After 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...
I'll never get tired of these. (courtesy of Sebasitan Wittekindt doi.org/10.1101/2025...)
New 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...
✨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/...
Functional maps of a genomic locus reveal confinement of an enhancer by its target gene
Genes 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...
science.org
New 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/
Excited 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...
Genetic and epigenetic screens in primary human T cells link candidate causal autoimmune variants to T cell networks - Nature Genetics
Massively 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 ...
nature.com
SCN2A 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/eGU0W
CRISPR activation for SCN2A-related neurodevelopmental disorders
Nature - 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...
rdcu.be
Google 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
CloneSelect 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...
A multi-kingdom genetic barcoding system for precise clone isolation - Nature Biotechnology
A barcoded CRISPR base editing system isolates target clones from complex mammalian, yeast and bacterial populations.
nature.com
⏰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/
