Matt
@mtcjh
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Computational bio at @ProfluentBio | @UCSF PhD @JoeBondyDenomy lab
San Francisco
Joined December 2017
Excited to share an exciting discovery which I think will help us understand the anti-phage arsenal of bacteria! https://t.co/zuXz5XhY7d 1/
biorxiv.org
Bacteria use a diverse arsenal of anti-phage immune systems, including CRISPR-Cas and restriction enzymes. Identifying the full defense repertoire of a given species is still challenging, however....
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Excited to share our last collab paper, now out in print @ScienceMagazine!🎉 We reveal how dITP synthesis activates a SIR2 NADase effector to block phage infection! 🛡️🧬 https://t.co/pcBDNqW9zq
science.org
Signaling from pathogen sensing to effector activation is a fundamental principle of cellular immunity. Whereas cyclic (oligo)nucleotides have emerged as key signaling molecules, the existence of...
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Check out our new paper describing rAcrVIA1: an RNA anti-CRISPR that mimics guide RNAs to inhibit Cas13. Very fun project with stellar UW undergrad Victoria Hayes and collaboration with Ning Jia's group!
science.org
To circumvent CRISPR-Cas immunity, phages express anti-CRISPR factors that inhibit the expression or activities of Cas proteins. Whereas most anti-CRISPRs described to date are proteins, recently...
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What could scaling unlock for biology? Introducing ProGen3- our next AI foundation models for protein generation. We develop compute-optimal scaling laws up to 46B parameters on 1.5T tokens with real evidence in the wet lab. +we solve a new set of challenges for drug discovery
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Claire's paper now entitled "Multi-interface licensing of protein import into a phage nucleus" is now published here: https://t.co/ke6OpnHR85
@CKokontis used classic genetics to figure out how proteins are selected for import into a "phage nucleus" Some notable additions:
nature.com
Nature - This study uncovers a highly conserved jumbo phage protein, Imp1, that possesses multiple interfaces to license protein import into a proteinaceous nucleus-like compartment, using a...
New preprint from the lab, led by outstanding student Claire Kokontis! (@CKokontis) In this work Claire et al. discover Imp1-Imp6, phage proteins required for the selective import of proteins into the jumbo phage nucleus! Imp1 (below) is the special one. https://t.co/dtmUfpV8uk
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Can LLMs exert molecular control in modulating protein-DNA interactions? New research where we demonstrate AI can reprogram DNA recognition of gene editors-- all in single-shot without iterative laboratory screening. Incredible positive impact to unlock
1/ Today we announced new research in the ability of AI models to precisely modulate protein-DNA interactions without iterative lab screening. 🧵
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🌟Our latest results are now published at NAR🌟 https://t.co/yWciP3vC0n. We hope that AntiDefenseFinder will enable scientists to further uncover the natural diversity of inhibitors (or regulators) of known bacterial defense systems. Recap below!
academic.oup.com
Abstract. The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification of defense and anti-defense systems ali
Excited to introduce AntiDefenseFinder - a free, open source tool that detects anti-defense systems in any genomic sequence. Available here to toggle on/off: https://t.co/2Z08fGyQLD. Read below for our insights into the >47K detectable systems📈
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I am very proud to share our paper on Tad1/Tad2 sponges, which appeared to be multifunctional anti-defense proteins that inhibit many different signaling-based immunity systems!💫 https://t.co/K6UvnskoW8
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I'm thrilled to share that I've joined Dr. Pam Ronald’s lab at @ucdavis to study how plants evolve multi-pathogen resistance, and in the long-term, build upon sustainable agriculture practices. As pivot into this field, I'd love to connect w/ folks in the ag & climate space!🌱🌎
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Tomorrow, 9/17 @ 4pm ET, we'll have @jeffruffolo @ProfluentBio present ProseLM: Adapting protein language models for structure-conditioned design Sign up on our website to receive zoom links via email or DM us to join! Read the paper:
biorxiv.org
Generative models for protein design trained on experimentally determined structures have proven useful for a variety of design tasks. However, such methods are limited by the quantity and diversity...
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The final version of our paper on anti-CRISPRs "in disguise" as Cas proteins is out today in Nature! Congrats to Mark, Edith and the whole team!
nature.com
Nature - We demonstrate that phages have co-opted cas genes from CRISPR defence systems, which subsequently evolved anti-defence functions.
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My favorite and hardest NMR experiment ever conducted is finally out! Congrats to everyone involved, but especially Daphne for pushing the project to the end 🎉🎊
Anti-CRISPR enzyme is widespread, specific and potent: as good or better for lytic rep and lysogen stability than a strong non-enzyme! Long running effort in @fraser_lab/BD lab with many contributors (co-led by Daphne Chen and @leahtangroe). https://t.co/FAjO4ahAOi
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Glad this is finally out! 🛡️AntiDefenseFinder 🔎🦠 will identify over 150 defense inhibitor families across MGEs, phages, and prokaryotes. Update DefenseFinder to v1.3.0 to use. Congrats Florian and @ErinHuiting!
Excited to introduce AntiDefenseFinder - a free, open source tool that detects anti-defense systems in any genomic sequence. Available here to toggle on/off: https://t.co/2Z08fGyQLD. Read below for our insights into the >47K detectable systems📈
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For antibodies, we started with the clinically approved PD-1 binder nivolumab, focusing design on either the CDR loops or framework. We obtained a wide range of binders from each approach, including two antibodies with nearly 3-fold higher affinity for PD-1 than nivolumab.
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For gene editors, we started with a low-activity base editor previously designed using LMs, then focused design on either active site or non-active site residues. Both yielded base editors with 50% higher A-to-G editing, approaching SOTA editors in just one round of optimization.
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Protein structural search uncovers an ancestral Cas13 protein led by the brilliant @PeterHYoon !! Check out the paper and thread! 👇
Excited to share our work published in @ScienceMagazine today answering the question: “Where does Cas13 come from?” https://t.co/twJmttYYkx
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I am thrilled to start my lab as an assistant professor @biozentrum & @NCCR_AntiResist of @UniBasel_en this fall. I will continue my research interest in bacteria & jumbophage interactions. Equally thrilled to be closer to our families after 10+ years.
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Did you see the bridge RNA papers yesterday? Bacterial transposons promote programmable, RNA-guided DNA recombination. Remarkably, we found that the recombinase was co-opted in archaea and eukaryotes for widspread RNA-guided RNA modification, an essential function in humans!
New preprint: In a fun collaboration with the @SternbergLab, we reveal the evolutionary origin of eukaryotic RNA-guided RNA modification (Nop5 and Prp31) in recently characterized bacterial IS110-family transposons. https://t.co/W6W3nYU7HB
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Next Tuesday, 5/07 @ 4 pm EST, we're very excited to have @jeffruffolo @stephennaybach from @ProfluentBio present OpenCRISPR! Read the paper here: https://t.co/RUgkQx1va0 Sign up on our website to get the Zoom link via email next week!
biorxiv.org
Gene editing has the potential to solve fundamental challenges in agriculture, biotechnology, and human health. CRISPR-based gene editors derived from microbes, while powerful, often show significant...
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