iiinova — where your digital self keeps evolving

11/ A huge thanks to the National Science Foundation for their foundational grant support of this research. Big shoutout to Liyuan Liu, Charlotte Rochereau, Simon @sim0nsays.bsky.social, Guillaume @gogurtecho.bsky.social for leading this project w/ Sergey @sokrypton.org and his group @mit.edu.

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10/ This is an important milestone for us, but also just the start. Building a complete 19 amino acid organism remains a major goal, w/ many open questions about genome-wide recoding, fitness, evolution, and the design rules of modern and early life. Lots of fun work ahead!

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9/ We installed 21 subunits in one location of the E. coli genome -> this Ec19 bacteria lived and was evolutionary stable for hundreds of generations without reverting back to any isoleucine residues!

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8/ Through a lot of hard work and troubleshooting by the team, we were able to individually recode all 50+ ribosomal subunits to replace all 382 isoleucine residues. Some functional AI designs were pretty wild, like this RpSJ where an entire stretch was replaced.🤯

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7/ We set out to remove all 382 isoleucine residues from the ribosome -- the cell's molecular factory. The ribosome is the most complex and one of the most important protein in the cell... If we can recode the ribosome, then we can likely do the rest of the proteome.

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6/ We explored different protein language models (ESM, MSATr) and structure-based sequence models (MPNN, AlphaFold Design) to computationally generate isoleucine-less proteins!

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5/ Can proteins with complete I-to-V or I-to-L substitutions function? ... We tested a bunch, but only ~40% of the proteins worked. So how do we get rid of Isoleucine in the rest of these proteins? ... We developed a Design-Build-Test loop and powered the protein design with AI.

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4/ Isoleucine is also more costly than Valine or Leucine (L) to produce -- an energetic saving for the cell if we can get rid of isoleucine entirely! ⛽️ 🫰

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3/ 🤔 So which amino acid (AA) can we get rid of ?🗑️ Based on AA conservation analysis across all proteins, the branched chain amino acids (BCAAs) are the most frequently mutated, with Isoleucine (I) to Valine (V) being the most tolerated substitution overall.

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Harris Wang @harriswang.bsky.social · 10/03/2026

2/ This work asks a simple but fundamental question: ❓Can life be built with fewer than the 20 standard amino acids used by all organisms on Earth 🌎 today? Achieving this would rewrite the molecular building blocks of life itself.

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SEED2026 abstract deadline extended to 3/15!! there's still time to submit an abstract for a talk or poster! #SEED2026 #synbio

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Harris Wang @harriswang.bsky.social · 05/03/2026

SEED 2026 Abstract due in 3 days! We've got an excellent line up of keynotes & invited speakers. Join us to present your work & hear the latest SynBio breakthroughs. A major theme this year is AI+Bio! 🧬🔬🤖💻🦠 synbioconference.org/2026

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Reposted by Harris Wang

Innovative Genomics Institute @innovativegenomics.bsky.social · 27/10/2025

We're excited to help launch the inaugural Gordon research conference on #microbiome editing, coming up in January in Pomona, CA! Learn more and register here: ow.ly/a6Am50X9XkE

illustration of petri dishes growing different microbes

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We are excited for many apps of Foli-seq in academia & industry. Please reach out to collaborate! Lots of exciting projects in this space for students & postdocs. Led by Yiming @yiminghuang.bsky.social and Yiwei @yiweisun.bsky.social & thanks to all our collaborators! @columbiasysbio.bsky.social

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In 💩 samples from patients with Inflammatory Bowel Disease (IBD) from the @crohnscolitisfdn.bsky.social, we can distinguish different patient cohorts with increase clinical severity of disease and stratifying biomarkers that associated with immune pathway involvement.

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Each day, humans shed billons of host cells from the gut lining out of the body (our "exfoliome") via our poop. Foli-seq unlocks this non-invasive exfoliome analysis to assess gut and immune functions, and links with the gut microbiome, all w/o colonoscopy or tissue biopsy. 💩🧬

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Fecal exfoliome sequencing captures immune dynamics of the healthy and inflamed gut - Nature Biotechnology

Introducing Foli-seq in @natbiotech.nature.com today. Foli-seq can be used to measure gut-derived RNA from fecal matter (signals of immune, secretory & epithelial cells). We used this to map gut inflammation, drug response, and host-microbe interactions. 💩🧬💊🦠 www.nature.com/articles/s41...

nature.com

Profiling host RNA shed in feces reveals disease states in the gut.

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Harris Wang @harriswang.bsky.social · 15/11/2025

📢 Our Dept. of Systems Biology at Columbia University has an open tenure-track Assistant Professor position in the broad area of quantitative biology. Come join our awesome department in NYC! Please circulate. apply.interfolio.com/177622 Suggested deadline: 12/15/2025. @columbiasysbio.bsky.social

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Reposted by Harris Wang

Sternberg Lab @sternberglab.bsky.social · 14/11/2025

1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge. Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...

science.org

Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases

Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...

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2026 Microbiome Editing Conference GRC

We are hiring PhD & Postdocs in this space so please reach out if interested. Also check out the Gordon Research Conference on Microbiome Editing in Jan 11-16, 2026. www.grc.org/microbiome-e...

grc.org

The 2026 Gordon Research Conference on Microbiome Editing will be held in Pomona, California. Apply today to reserve your spot.

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Precise virulence inactivation using a CRISPR-associated transposase for combating Enterobacteriaceae gut pathogens - Nature Biomedical Engineering

This new work in commensal microbes and our other recent work to engineer pathogenic bacteria to reduce virulence in the gut are greatly expanding our toolkit for in vivo microbiome editing. 🛠️🧬🦠 www.nature.com/articles/s41...

nature.com

A self-transmissible CRISPR-associated transposase system encodes a nanobody payload to treat Shiga toxin infections.

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Led by the stellar Diego Gelsinger @drgel.bsky.social working with many contributors through a wonderful long-term collab w/ Sam Sternberg & Ivo Ivanov labs! 🤝 @columbiauniversity.bsky.social @columbiasysbio.bsky.social

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Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases

Very excited to share our latest work in Science on metagenomic editing (MetaEdit) of the gut microbiome in vivo & directly modifying unculturable immune-modulatory SFB bug in the small intestine. 🦠🧬🛠️ www.science.org/doi/10.1126/...

science.org

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Harris Wang @harriswang.bsky.social · 25/06/2025

Grateful to work with the wonderful @vilcekfoundation.bsky.social and the super talented Hiroki Otsuka on a short manga highlighting our research and my journey as an immigrant scientist! 🧪🦠🧬 vilcek.org/news/microbe...

vilcek.org

Biographical Manga Highlights Scientist Harris Wang’s Superhero Microbiome Work

Discover how immigrant scientist Harris Wang, PhD, uses synthetic biology to reprogram gut bacteria in this manga by Hiroki Otsuka.

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Harris Wang @harriswang.bsky.social · 03/02/2025

Happy to share our new paper in @naturemicrobiol.bsky.social on mapping spatial relationships of the human gut microbiome. We identified distinct spatial hubs between gut bacteria that reflect sub-community assemblies at the micron-scale. Led by Miles Richardson & co. www.nature.com/articles/s41...

nature.com

SAMPL-seq reveals micron-scale spatial hubs in the human gut microbiome - Nature Microbiology

Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) can be applied to complex microbial communities to reveal spatial co-localization of microbes at the micron scale.

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Harris Wang @harriswang.bsky.social · 16/12/2024

I hear ya! I mean more on the “we” rather than “I” personally in some of these sentiments. Again, this is not meant as a substitute for things we do or aught to do already but something that can augment. Also, just an idea to stimulate conversations.

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Harris Wang @harriswang.bsky.social · 15/12/2024

I like your ideas, just trying to think of ways that I can donate my “time” to help specific labs/areas that might even be outside of my immediate area of expertise. Seems like having a universal currency for science might have some uses. It’s obviously imperfect, but maybe could refine the ideas.

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Harris Wang @harriswang.bsky.social · 15/12/2024

I think the idea is that you can compensate others with your credits/tokens like pay for reagents (service contracts on equipment!!). There are lots of misc expenses in running a lab that add up!

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Harris Wang @harriswang.bsky.social · 15/12/2024

May not push the incentives to a point where people will review more, but at least extend the effort of the review to benefit not only the authors (or the journals) but broaden impact to others through the peer review process. It’s like volunteering time and using earned credits to give to others.

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The problem is that people don’t have time to review. It’s not clear how you easily “fact check” papers in bio (unless there are massive flaws). Critiques of strengths & weaknesses are still useful. Most people aren’t volunteering time to review biorxiv papers. Maybe this system can be an incentive.

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Credits used back to invest in science community rather than on direct personal benefit.

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I recognize that this idea is still underdeveloped but wanted to start share it here. Would love to hear feedback and find people willing to help do something like this! Thanks for reading! (9/9)

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I can imagine this framework on a blockchain to track credits or tokens and you can have people invest in buying the tokens directly to further add to this community (basically a donation). Lots of ways to grow this organically. The economics need to be figured out in more detail. (8/9)

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Importantly you can DONATE these credits to other labs or entities. What if there’s a cool project from another lab that I want to support? I can donate my science credits to them so it can advance the science. You basically converted ↔️ PR time/effort into communal goods for sharing w/ others. (7/9)

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The SOLUTION:💡What if we gave reviewers some type of “science credits” after peer review. Sci-credits can be exchanged for all kinds of science related activities. For example: publication fees, society/conference fees, discount on purchasing reagents or repair cost of equipment. (6/9)

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The NEED: a fair, equitable, and transparent framework to compensate referee’s time and effort in peer review 👍. This could help make PR higher quality, attract better reviews and more motivated reviewers (maybe?) (5/9)

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Direct cash 💵 compensation for PR is not good as it has obvious perverse incentives. But most people hate to review a paper (for “free”) and then later get charged $10k+ to publish in a journal. Some journals have small discounts, but those don’t move the needle. (4/9)

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But most referees 🧑‍💻 agree to review a paper out of sense of duty, perceived obligation to the journal/editor, the topic area, the specific paper, or even the authors (or combo of the above). Some people do more PR than others. Most people I know don’t review 3x the # of papers they publish/yr. (3/9)

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The PROBLEM: Peer review (PR) is poorly incentivized. Reviewing papers take time, no one has time⌛️, and referees don’t get properly compensated for this work (often hours to days, stretched over months to years). People participate in PR because it’s a ‘communal good’ to keep science going. (2/9)

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