@BashorLab

Bashor Lab in Houston, Texas | Mammalian Synthetic Biology et al.

 Houston, TX
bashorlab.rice.edu/
Joined December 2022
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  • Followers1K
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We are pleased to share a paper from our lab out in this week’s issue of @Nature, where we show that HT + ML can dramatically speed up the synbio DBTL cycles, profiling gene circuit design spaces at unprecedented scale: nature.com/articles/s41586-0… (1/16)

Ultra-high-throughput mapping of genetic design space

Nature - CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary...

nature.com
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Kaiyi Jiang
@idmjkyOct 19
Generative protein design is transforming macromolecular drugs, but de novo designed therapeutics could still be hindered by immunogenicity in the clinics. Excited to introduce MESSI, a discrete diffusion model for generative protein deimmunization.
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Lingchong You@lingchongyouOct 8
1/ Even bacterial communities can get caught in a bad romance they just can't get over. A brief encounter with antibiotics can leave a lasting ecological memory of resistance plasmids persisting for weeks after the drug is gone. @DukeBiodesign @DukeUBME nature.com/articles/s41467-0…

Ecological memory of prolonged plasmid persistence after transient antibiotic exposure

Nature Communications - Zhou, Weiss and colleagues show that a brief antibiotic pulse can prolong plasmid persistence by removing plasmid-free competitors, creating an ecological memory that may...

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Warmflash lab@WarmflashLabOct 7
Happy to share our latest preprint in collaboration with @BashorLab. Great work by first author Alena Streletskaia. biorxiv.org/content/10.64898…
Circular stem cell colonies with BMP activated on one side. Brachury and N-CAD positive cells are seen migrating from the light-induced source.

ALT Circular stem cell colonies with BMP activated on one side. Brachury and N-CAD positive cells are seen migrating from the light-induced source.

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Highly multiplexed mammalian metabolic engineering with a shotgun approach - @sudpinglay @JefBoeke nature.com/articles/s41587-0…
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Tom Ellis@ProfTomEllisSep 25
There's going to be so much cheap lab automation equip. on LabX in 2 to 3 years, when either all these new self-driving AI wetlabs fold, or they realise that current lab automation equip. sucks for what they need to do.
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Beautiful work from Ron Weiss and team - a significant step forward for ML-driven design of synthetic circuits. biorxiv.org/content/10.64898…

Generative Neuromorphic Programming of Mammalian Cells

Cells make decisions through densely interconnected regulatory networks that compute graded, analog responses[[1][1], [2][2]]. Synthetic biology has made cells programmable, but the field’s dominant...

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Xinchen Wang@xinchen_wSep 20
AI in biology may have a data problem before it has a model problem. It’s easy to use AI to make drug discovery faster & more efficient. The much harder challenge is discovering impactful medicines humans would never have found. AI models are only as useful as the data they learn from, and it’s especially hard in biotech. The biggest and most valuable goals in AI in biotech are to cure diseases we haven’t been able to cure and design therapeutics capable of doing things that haven’t been possible before. By definition, these goals aren’t represented in our training data. For our second essay at Waypoint Bio, we wrote about the data we think we’ll need to build out-of-distribution medicines: waypointbio.com/writings

Writings

Waypoint Bio harnesses high throughput and high resolution technologies to advance cell therapy, compressing years of work into a single experiment.

waypointbio.com
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Cell–cell interactions are key to all biological processes, but there hasn't been a good way to perform inter-cellular screens for genetic regulators of these interactions in vivo. We developed match-seq (multiplexed associative tagging of cell interaction histories) - using engineered virus-like particles to transfer barcoded mRNAs from 'sender' to neighboring 'receiver' cells, so you can reconstruct cellular interactions with sequencing alone, no imaging required. We coupled match-seq with CRISPR + scRNA-seq in cancer, revealing cancer-immune interaction neighborhoods at scale, and new cancer genes that can be targeted for tumor rejection via immune cell interactions. Led by the brilliant @peterdu_ with Bassik lab! biorxiv.org/content/10.64898…
Peter Du@peterdu_Sep 19
CRISPR screens are great at telling you what a gene is doing inside your cells. But what if you're interested in what's happening to its neighbors? Today, I'm excited to share match-seq, a new method that deciphers cell-cell interactions using barcoded RNA transfer. 1/9
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Furqan Fazal@FurqanMFazalSep 1
Excited to share our latest work, led by Surbhi Sharma! We study the kinetics of RNA localization to the outer mitochondrial membrane (OMM), building on our 2019 APEX-seq work showing that hundreds of RNAs go to the OMM for local translation. biorxiv.org/content/10.64898…
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Steven Banik@StevenMBanikSep 1
Excited our ratiometric transcriptional activation (RTA) work led by @Melissa_Gray234 is out online today @CellCellPress! Measurements determine what we can discover in biology; we use RTA to turn protein abundance changes into amplified signals. cell.com/cell/fulltext/S0092…

Ratiometric transcriptional activation by protein degradation

By tethering a protein of interest to anti-CRISPR, protein degradation is transformed into amplified and programmable transcriptional outputs via Cas-based transcription factors, with sensitivity to...

cell.com
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Excited to share our new preprint! We asked how inducible SynNotch-CAR circuits can better discriminate on-target from off-target cells when they share similar antigens. biorxiv.org/content/10.64898… Congratulations to Daniel Hoces, Jaclyn Ng and Julian Perez!
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1/ Let’s face it: we synthetic biologists are control freaks. We want every component to do exactly what we intend and nothing else. Our new paper asks what happens if we stop fighting biological “messiness”. @DukeBiodesign @DukeUBME nature.com/articles/s41467-0…

Engineering microbial consortia for distributed signal processing

Nature Communications - Multiplexed biosensing is often limited by crosstalk between sensors. Here, authors distribute sensing across microbial communities and use timer-resolved modelling and...

nature.com
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Controlling the transcription with the DNA… that stays outside of the cell? Introducing LUNAR, a chemogenetic receptor gated by DNA for sensing applications. This complex project was led by @BoaoXia with collaborators @aliceyting and @nkalogriopoulos. biorxiv.org/content/10.64898…
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Qiao Liu@liuqiao_Aug 21
Excited to share our new preprint: RegFM, an interpretable context-aware foundation model for human transcriptional regulation. 🧬 There are already a lot scFMs and DNA FMs in the field. We ask: Can a genomic FM understand both DNA sequence and the underlying cellular context?
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We've long wondered what gives NETs their branched architecture. Working with @SCWestLab, @DArmstrongJames we found that RAD51—a protein involved in DNA repair—promotes NET branching & stability, spatially restricting NETs to control type-2 inflammation. science.org/doi/10.1126/scie…

RAD51 stabilizes neutrophil extracellular traps to compartmentalize inflammation

Neutrophil extracellular traps (NETs) feature a branched chromatin architecture whose origin and function remain unknown. We found that NET branching is mediated by RAD51, a protein generating DNA...

science.org
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Jay Shendure@JShendureJul 31
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
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nature
@NatureJul 30
Nature research paper: Sequential reading of a stepwise-shortened peptide immobilized on nanopore go.nature.com/4h4kaHk

Sequential reading of a stepwise-shortened peptide immobilized on nanopore

Nature - A nanopore-based ‘chop and measure’ method sequences peptides at single-amino-acid resolution by using enzymatic digestion to progressively shorten the N terminus one...

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Peter Koo@pkoo562Jul 27
Our review is now published in @NatureGenet! We cover all aspects of modeling regulatory genomics, from loss landscapes to OOD generalization to model interp to fixing generalization issues using perturbation data via active and continual learning! nature.com/articles/s41588-0…

Toward generalizable and interpretable AI in regulatory genomics

Nature Genetics - This Review surveys the current landscape of genomic artificial intelligence through the lens of sequence-to-function models, examining how architectural choices, training data,...

nature.com
Peter Koo@pkoo562Feb 3
Excited to share a new Review: "Toward Interpretable and Generalizable AI in Regulatory Genomics" with @msyk_nagai @Al_Murphy_ @kae_rizzo We lay out the landscape of AI x Genomics and offer an opinionated perspective on where the field should go! arxiv.org/abs/2602.01230

Toward Interpretable and Generalizable AI in Regulatory Genomics

Deciphering how DNA sequence encodes gene regulation remains a central challenge in biology. Advances in machine learning and functional genomics have enabled sequence-to-function (seq2func)...

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jared toettcher@toettchJul 24
New Toettchlab paper alert! Harrison Oatman just published his beautiful work combining software design for "smart" microscopy+optogenetics and some really beautiful work understanding EGFR-driven collective cell migration. cell.com/cell-systems/fullte…
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Introducing a phospho-switch for allosterically regulating target proteins in response to ERK kinase activity. @toettch nature.com/articles/s41592-0…

Design and optimization of a kinase-controlled allosteric switch

Nature Methods - This Article introduces a phospho-switch for allosterically regulating target proteins in response to ERK kinase activity.

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