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The Dark Matter Project

@darkmatterproject.bsky.social
133 followers 63 following 47 posts

Studying The Dark Matter of the Genome - everything noncoding 🧬 A collaborative scientific project at NYU Langone. Account managed by Ran Brosh.

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The Dark Matter Project @darkmatterproject.bsky.social · 13h
www.nature.com/articles/s41... Highly multiplexed mammalian metabolic engineering with a shotgun approach. Congrats Julie Trolle, Sud Pinglay, Jef Boeke et al!
nature.com
Highly multiplexed mammalian metabolic engineering with a shotgun approach - Nature Biotechnology
Metabolic engineering of mammalian cells is simplified and scaled by screening ‘shotgun’ modifications.
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The Dark Matter Project @darkmatterproject.bsky.social · 24/09/2026
Tue Oct 27, 11:30 AM–1 PM ET · Thu Oct 29, 1–2 PM ET. Both include audience Q&A. Co-moderated by Jef Boeke, Ran Brosh & Carolyn Chapman. Part of NYU Langone’s “Rewriting Life” series. Recordings will be available. #Bioethics #Conservation #SciSky
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The Dark Matter Project @darkmatterproject.bsky.social · 24/09/2026
How can genome engineering support ecosystem health? What are the ethical considerations? How is it regulated? Free webinars: 🧬 Oct 27: Science talks by Ben Novak & Beth Shapiro ⚖️ Oct 29: Ethics, regulation & governance panel w/ Art Caplan, Alex Erwin & Larisa Rudenko Register: bit.ly/46GXlTQ
Flyer for two free webinars from NYU Langone’s Center for Synthetic Regulatory Genomics: Vertebrate Genome Engineering for Ecosystem Health — Scientific Innovation (Oct 27) and Ethics, Regulation and Governance (Oct 29). Registration: https://bit.ly/46GXlTQ.
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The Dark Matter Project @darkmatterproject.bsky.social · 22/08/2026
ZATELLITE: a toolkit to visualize and manipulate human centromeres in live cells using synthetic zinc fingers biorxiv.org/content/10.6... Congrats to Nestor Saiz et al. from the Center of Synthetic Regulatory Genomics!
biorxiv.org
ZATELLITE: a toolkit to visualize and manipulate human centromeres in live cells using synthetic zinc fingers
Changes in the number of chromosomes or their spatial organization within the nucleus have critical consequences for cell fate. Yet capturing the karyotype or three-dimensional architecture of chromat...
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The Dark Matter Project @darkmatterproject.bsky.social · 06/07/2026
Synthetic biology and genome engineering in support of human, agricultural, and environmental security doi.org/10.3389/fbio... Check out the latest Perspective by Carolyn Chapman et al.
doi.org
Frontiers | Synthetic biology and genome engineering in support of human, agricultural, and environmental security
The rapid pace of innovation in synthetic biology and genome engineering elicits a need to reevaluate systems of oversight to ensure that biosafety and biose...
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The Dark Matter Project @darkmatterproject.bsky.social · 22/06/2026
Tomorrow! bit.ly/4urIZQH
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The Dark Matter Project @darkmatterproject.bsky.social · 18/06/2026
Happening next week - register now: bit.ly/4urIZQH Learn from world leaders in the fields of Xenotransplantation science, ethics and regulation!!!
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Reposted by The Dark Matter Project
The Dark Matter Project @darkmatterproject.bsky.social · 10/06/2026
Interested in the Science, Ethics and Regulation of Xenotransplantation? Join the next sessions in the "Rewriting Life" series! Register here: bit.ly/4urIZQH
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The Dark Matter Project @darkmatterproject.bsky.social · 10/06/2026
This webinar series is supported by NHGRI's Centers of Excellence in Genome Science Program and is hosted by the Institute for Systems Genetics at NYU Langone Health
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The Dark Matter Project @darkmatterproject.bsky.social · 10/06/2026
The 2nd session, on Jun 25, 12:15 PM (ET), will focus on ethics and regulation, featuring Heather Lombardi (Director, Global Regulatory Affairs & Policy-Biologics, United Therapeutics) and Brendan Parent (Associate Professor, NYU Grossman School of Medicine).
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The Dark Matter Project @darkmatterproject.bsky.social · 10/06/2026
The first session, on Jun 23, 12 PM (ET) will feature David Ayares (Sr. Vice President, Xeno R&D, United Therapeutics), a pioneer in genetic engineering of pigs for xenotransplantation, as well as other mammalian species and applications.
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The Dark Matter Project @darkmatterproject.bsky.social · 10/06/2026
Interested in the Science, Ethics and Regulation of Xenotransplantation? Join the next sessions in the "Rewriting Life" series! Register here: bit.ly/4urIZQH
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Reposted by The Dark Matter Project
bioRxiv Genetics @biorxiv-genetic.bsky.social · 02/07/2025
Assemblatron: An Automated Workflow for High-Throughput Assembly of Big-DNA Libraries www.biorxiv.org/content/10.1101/202…
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The Dark Matter Project @darkmatterproject.bsky.social · 19/05/2026
Happening this Wednesday, 2 PM ET! Register here: nyulangone.zoom.us/webinar/regi...
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The Dark Matter Project @darkmatterproject.bsky.social · 06/05/2026
Please join us for the “Rewriting Life” series kickoff webinar on May 20th, 2026, 2-3 PM (ET). Register here: nyulangone.zoom.us/webinar/register/WN_tyBjjq2WTHytv_nyovzV9w
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The Dark Matter Project @darkmatterproject.bsky.social · 15/05/2026
Synthetic Regulatory Genomics pmc.ncbi.nlm.nih.gov/articles/PMC...
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Addgene @addgene.bsky.social · 14/05/2026
We appreciate you sharing your improved toolkit with us! 💙🧑‍🔬 Find the plasmids here: www.addgene.org/browse/artic...
addgene.org
Addgene: Improved vector toolkit for genome writing in mammalian cells.
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The Dark Matter Project @darkmatterproject.bsky.social · 13/05/2026
Plasmids described in this manuscript are now on Addgene. Check out our Resources page for more info: www.thedarkmatterproject.org/resources
thedarkmatterproject.org
Resources — The Dark Matter Project
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The Dark Matter Project @darkmatterproject.bsky.social · 13/05/2026
Improved vector toolkit for genome writing in mammalian cells www.biorxiv.org/content/10.6...
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The Dark Matter Project @darkmatterproject.bsky.social · 13/05/2026
Want to deploy Big-IN or mSwAP-In in your own lab? Check out new plasmids we deposited on Addgene as well as updated protocols: www.thedarkmatterproject.org/resources
thedarkmatterproject.org
Resources — The Dark Matter Project
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The Dark Matter Project @darkmatterproject.bsky.social · 06/05/2026
Please join us for the “Rewriting Life” series kickoff webinar on May 20th, 2026, 2-3 PM (ET). Register here: nyulangone.zoom.us/webinar/register/WN_tyBjjq2WTHytv_nyovzV9w
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The Dark Matter Project @darkmatterproject.bsky.social · 17/03/2026
Improved vector toolkit for genome writing in mammalian cells www.biorxiv.org/content/10.6...
biorxiv.org
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The Dark Matter Project @darkmatterproject.bsky.social · 29/01/2026
Mammalian genome writing: Unlocking new length scales for genome engineering www.sciencedirect.com/science/arti...
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Sudarshan Pinglay @sudpinglay.bsky.social · 23/01/2026
Happy to share that our review on mammalian genome writing with Jack Atwater, Ran Brosh, Jef Boeke, @jshendure.bsky.social and Matt Maurano is now out in @cellpress.bsky.social! www.sciencedirect.com/science/arti...
sciencedirect.com
Mammalian genome writing: Unlocking new length scales for genome engineering
The ability to design and engineer mammalian genomes across arbitrary length scales would transform biology and medicine. Such capabilities would enab…
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The Dark Matter Project @darkmatterproject.bsky.social · 20/01/2026
🧬Sign up to our free online 2026 Genome Writing Workshop 🧬 www.thedarkmatterproject.org/2026-genome-...
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The Dark Matter Project @darkmatterproject.bsky.social · 05/01/2026
www.biorxiv.org/content/10.6... Congrats to Dr. Noor Chalhoub who managed to defend her thesis and publish this paper on the same day!
biorxiv.org
Genome writing and Targeted Delivery of the NKX6-3/ANK1 gene cluster and its Type 2 Diabetes GWAS Variants to Human iPSCs
Genome-wide association studies (GWAS) identified over 600 loci containing single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D), most of which reside in non-coding regions. Amo...
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The Dark Matter Project @darkmatterproject.bsky.social · 22/12/2025
Enhancer cooperativity in the folded genome www.sciencedirect.com/science/arti...
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The Dark Matter Project @darkmatterproject.bsky.social · 09/12/2025
Structure and evolution-guided design of minimal RNA-guided nucleases www.biorxiv.org/content/10.6...
biorxiv.org
Structure and evolution-guided design of minimal RNA-guided nucleases
The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome editing capabilities. However, generating diverse multi-domain proteins with robust enzymatic...
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The Dark Matter Project @darkmatterproject.bsky.social · 06/12/2025
High-fidelity human chromosome transfer and elimination | Science www.science.org/doi/abs/10.1...
science.org
High-fidelity human chromosome transfer and elimination
The synthesis of human genomes and other gigabase-scale genomes will require new strategies. Here, we realized key steps in our pipeline for building synthetic human chromosomes. We established: (i) t...
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
Did it work? Hell yeah! Read our two companion preprints to learn more: bsky.app/profile/dark...
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
This recombination fuses mouse Taf1's exons 1-24 with human TAF1's exons 25-38 to form a fully functional gene that encodes mouse TAF1 protein. The recombination also removes all marker cassettes, making the final "converted" allele scarless.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
The final step of engineering is what we call "conversion". It includes introducing Cre enzyme that induces recombination between the 1st loxP site in mouse Taf1 intron 24, and a 2nd loxP site located in human TAF1 intron 24.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
This feat of engineering was performed using a variant of a method we recently published called mSwAP-In (mammalian switching antibiotic resistance markers progressively for integration). www.nature.com/articles/s41...
nature.com
Mouse genome rewriting and tailoring of three important disease loci - Nature
This study describes a method to insert large stretches of exogenous DNA into mammalian genomes, which is used to insert human ACE2 loci into mouse to produce a model of human SARS-CoV-2 infection.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
Next, we engineered mouse embryonic stem cells (mESCs), first with a loxP site in Taf1's intron 24, followed by integration of a marker cassette (a landing pad) downstream of the gene, and finally we replaced this cassette with the 78-kb human fragment.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
Using CREEPY (CRISPR-mediated editing of synthetic episomes in yeast) we've substituted every amino acid that is different between humans and mice so that the expressed protein would be identical to mouse TAF1. doi.org/10.1093/nar/...
doi.org
CREEPY: CRISPR-mediated editing of synthetic episomes in yeast
Abstract. Use of synthetic genomics to design and build ‘big’ DNA has revolutionized our ability to answer fundamental biological questions by employing a
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
But we were worried that the human TAF1 protein would be incompatible when expressed in mice (TAF1 is the largest subunit of the TFIID complex, a large protein group that is essential for initiating transcription of most genes).
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
We assembled this region from an XDP patient-derived BAC, using the superpower of S. cerevisiae (yeast), into a delivery-ready vector.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
The pathogenic SVA insertion is in TAF1's intron 32, but we wanted to generate a partially humanized mouse model, and decided to include a 78 kb human region that spans TAF1 exons 25-38, including all intervening introns and the SVA.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
Our solution? A "hybrid-convertible" allele:
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
This is the problem we had to tackle when we engineered the first mouse model of X-linked Dystonia Parkinsonism, a disease caused by an SVA (SINE-VNTR-Alu) retrotransposon insertion in the essential TAF1 gene.
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
The answer is quite simple of course: make it conditional. But what if the lethality is induced by a 2.7 kb retrotransposon insertion into an X-linked gene? How would you CONDITIONALLY introduce this element?
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The Dark Matter Project @darkmatterproject.bsky.social · 29/10/2025
How could one engineer a mouse carrying a LETHAL allele? A thread 🧵
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The Dark Matter Project @darkmatterproject.bsky.social · 25/10/2025
One step closer to an LLM that understands novel DNA🧬 𝗜𝘁𝗲𝗿𝗮𝘁𝗶𝘃𝗲 𝗶𝗺𝗽𝗿𝗼𝘃𝗲𝗺𝗲𝗻𝘁 𝗼𝗳 𝗱𝗲𝗲𝗽 𝗹𝗲𝗮𝗿𝗻𝗶𝗻𝗴 𝗺𝗼𝗱𝗲𝗹𝘀 𝘂𝘀𝗶𝗻𝗴 𝘀𝘆𝗻𝘁𝗵𝗲𝘁𝗶𝗰 𝗿𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗴𝗲𝗻𝗼𝗺𝗶𝗰𝘀. pubmed.ncbi.nlm.nih.gov/41125441 Congrats Andre Ribeiro-Dos-Santos and Matt Maurano!
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Priya Prakash @pryprk.bsky.social · 24/10/2025
I am proud to share our work on X-linked Dystonia-Parkinsonism — a rare neurodegenerative movement disorder driven by a SINE-VNTR-Alu retrotransposon insertion in the TAF1 gene. Read our two companion papers: 🔹 www.biorxiv.org/content/10.1... 🔹 www.biorxiv.org/content/10.1... 🧵 Highlights below!
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The Dark Matter Project @darkmatterproject.bsky.social · 08/10/2025
Read more on our website www.TheDarkMatterProject.org
thedarkmatterproject.org
The Dark Matter Project
The Center for Synthetic Regulatory Genomics at NYU Langone Health is tasked with the study of the genome's Dark Matter - the noncoding DNA and its role in human diseases.
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The Dark Matter Project @darkmatterproject.bsky.social · 08/10/2025
Congrats to all authors, including Yu (Jeremy) Zhao, Ran Brosh, @liddelowsa.bsky.social, @jefboeke.bsky.social, Cris Bragg and others. This work was primarily funded by the Collaborative Center for XDP and NHGRI's CEGS program.
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The Dark Matter Project @darkmatterproject.bsky.social · 08/10/2025
In the 2nd preprint @pryprk.bsky.social et al. describe deep behavioral and histological analysis of XDP mice and reveal a surprising myelin pathology. www.biorxiv.org/content/10.1...
biorxiv.org
Myelin pathology is a key feature of X-linked Dystonia Parkinsonism
X-linked Dystonia-Parkinsonism (XDP) is a progressive, adult-onset neurodegenerative movement disorder that predominantly affects males of Filipino descent. The disease is caused by the insertion of a...
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The Dark Matter Project @darkmatterproject.bsky.social · 08/10/2025
In the 1st preprint Zhang et al. describe the engineering of the first XDP mouse model and the splicing defects induced by the presence of a pathogenic intronic SVA retrotransposon. www.biorxiv.org/content/10.1...
biorxiv.org
Genome writing to dissect consequences of SVA retrotransposon disease X-Linked Dystonia Parkinsonism
Human retrotransposon insertions are often associated with diseases. In the case of the neurodegenerative X-Linked Dystonia-Parkinsonism (XDP) disease, a human-specific SINE-VNTR-Alu subfamily F (SVA_...
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The Dark Matter Project @darkmatterproject.bsky.social · 08/10/2025
We're thrilled to publish 2 exciting preprints today on the molecular pathology of X-linked Dystonia Parkinsonism! biorxiv.org/content/10.1... AND biorxiv.org/content/10.1... @nyulangone.bsky.social
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The Dark Matter Project @darkmatterproject.bsky.social · 25/09/2025
Megabase-scale human genome rearrangement with programmable bridge recombinases | Science www.science.org/doi/10.1126/...
science.org
Megabase-scale human genome rearrangement with programmable bridge recombinases
Bridge recombinases are naturally occurring RNA-guided DNA recombinases that we previously demonstrated can programmably insert, excise, and invert DNA in vitro and in Escherichia coli. In this study,...
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