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Amir Mitchell

@amitchell.bsky.social

620 followers 260 following 370 posts

Systems biologist trying to disentangle host-drug-microbiome interactions | PI at UMass medical school | trying to keep the BS to a minimum (not always successful) https://mitchell-lab.umassmed.edu

mitchell-lab.umassmed.edu

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Amir Mitchell @amitchell.bsky.social · Nov 23

Why are some non-antibiotic drugs toxic to bacteria 💊☠️🦠? Do they work like standard #antibiotics (ABX)? Our latest work by @MarianaNoto published @ScienceMagazine addresses this fundamental question (1/n)
https://www.science.org/doi/10.1126/science.adk7368

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Amir Mitchell @amitchell.bsky.social · May 31

The (very real) cost of changing your research field. Absolutely true! But the freedom to pivot is one of the greatest things in this profession.
www.nature.com/articles/s41...

The pivot penalty in research - Nature

An analysis of millions of scientific papers and patents reveals a ‘pivot penalty’ when researchers shift direction, with the impact of studies decreasing rapidly the further they move from their prev...

www.nature.com

Amir Mitchell @amitchell.bsky.social · May 22

Great opportunity to participate in scientific outreach!

Mark O. Martin @markowenmartin.bsky.social · May 22

Starting to write to folks to consider appear on my #MattersMicrobial podcast. Would love an astrobiologist! Looking for other cool and #OMG #WTM microbial enthusiasts to appear. Happy to hear suggestions. I need to fill July and August.

Amir Mitchell @amitchell.bsky.social · May 5

Had a fantastic time with @markowenmartin.bsky.social’s on his #MattersMicrobial podcast (@microbetv.bsky.social). We discussed how to uncover the killing mechanisms of hundreds of antibacterials simultaneously and how #AI can transform the search for new antibiotics 🧪🦠💊
youtu.be/Wa0zd-TRCO8?...

Matters Microbial #89: Can AI Point Us to New Antibiotics

YouTube video by MicrobeTV

youtu.be

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Reposted by Amir Mitchell

Will Ratcliff @wcratcliff.bsky.social · Jan 29

Yo, micro/evo/qbio/physics of living systems/astrobiology/renegade cell bio folks- if you are interested in starting a feed, reply/repost this. Let's get the crew back together!

Sebastian S. Cocioba @atinygreencell.bsky.social · Jan 29

Would anyone be interested in starting a microbial evolution feed on here? EvoSky is rather organismal, which is great, but would love to see experimental evo folks' feeds too. Thoughts?

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Amir Mitchell @amitchell.bsky.social · Jan 26

Fascinating shift in the geography of drug development (excellent writing too!)

Niko McCarty @nikomccarty.bsky.social · Jan 25

If you haven't read this article yet, you should! Link here: atelfo.github.io/2024/12/20/...

I think Alex should write more because he's really, really great at it.

Will all our drugs come from China?

Personal site for posts about my interests: the biotech industry, medicine, molecular biology, neuroscience, biorisk, science, consciousness, AI, innovation, decision making, philosophy, games, sci-fi, probability, and forecasting (among other things). I write to learn, mostly about biotech.

atelfo.github.io

Amir Mitchell @amitchell.bsky.social · Jan 18

The inherent stochasticity of biological systems 😉

Amir Mitchell @amitchell.bsky.social · Jan 17

Interested in Antimicrobial Resistance & Quantitative Bio? Join a 3-day meeting+workshop with some of my favorite #AMR #QBio scientists this April (University of Exeter, UK). Register here: tinyurl.com/QAMR2025reg 🧪🦠

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Amir Mitchell @amitchell.bsky.social · Dec 28

Amazing book, shaped my worldview on Science. Kuhn’s genius was also in claiming that “paradigm shifts” are not purely logical, but are tainted by social & psychological factors. He claimed that established scientists are often conservatives resisting such shifts.

Amir Mitchell @amitchell.bsky.social · Dec 14

It was all code written in Matlab

Amir Mitchell @amitchell.bsky.social · Dec 14

Sure, email me I can attach a copy

Amir Mitchell @amitchell.bsky.social · Dec 14

The drug-drug similarity networks are based on how these drugs impact a library of E. coli mutants (profiles of resistance or sensitivity). We in fact show the chemical similarity fails to capture many of these similarities.

Amir Mitchell @amitchell.bsky.social · Dec 14

Beautiful detective work disentangling what is the actual trigger for cell death upon transcriptional arrest 🧪

Mike Lee @theleelab.bsky.social · Dec 13

We just posted a preprint about a death mechanism that we find truly surprising.

When you turn off transcription, cells die (duh!)... but did you know this happens due to loss of Pol II itself, not loss of Pol II activity!?!

preprint here and a thread (1/n): www.biorxiv.org/content/10.1...
🧪

Pol II degradation activates cell death independently from the loss of transcription

Pol II-mediated transcription is essential for eukaryotic life. While loss of transcription is thought to be universally lethal, the associated mechanisms promoting cell death are not yet known. Here,...

www.biorxiv.org

Amir Mitchell @amitchell.bsky.social · Dec 9

Never-have-I-ever seen technology racing forward as fast as #LMMs in the past two years. Watching the #openAI releases coming out in real-time in their twelves-days series is jaw dropping! 🤖🌊
www.youtube.com/playlist?lis...

12 Days of OpenAI - YouTube

12 days. 12 livestreams. A bunch of new things, big and small.

www.youtube.com

Amir Mitchell @amitchell.bsky.social · Dec 7

My only complain is that I feel a bit like Cassandra, from the greek mythology, barely anyone listens 😞

Amir Mitchell @amitchell.bsky.social · Dec 7

The ability of LMMs (chatGPT here) to *assist* in generating useful code for biologists a mind-blowing power multiplier 🤯! My advice to biologists at all career stages: Learn to code, its a superpower 🦸‍♀️🦹‍♂️ (simple example, counting fluorescent colonies isolated from mouse gut microbiome) 🧪🦠

Microscopy image of fluorescent colonies of E. coli after automatic image segmentation

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Amir Mitchell @amitchell.bsky.social · Dec 4

There is also a lot to be said about doing a "proper" postdoc in a good lab. It opens your eyes to different research directions, lab techniques, mentoring style, institutions, and so much more!

Amir Mitchell @amitchell.bsky.social · Dec 4

I absolutely agree!! So many of these positions end up going nowhere. They make sense only in *very* few use cases (5-10%): it's a *real* program with real legacy of successful PIs, the candidate continues on their phd research trajectory, and the candidate is scientifically mature (rare).

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Amir Mitchell @amitchell.bsky.social · Dec 2

Credit for this work goes to my former student Dr Emily Lowry. Emily literally submitted the revised version of this manuscript at the very last minute before leaving the lab 🥳 (9/9)

Amir Mitchell @amitchell.bsky.social · Dec 2

I love this work since it a wonderful demonstration of (1) Serendipity in research – it started unexpectedly when we saw an active reporter even in non-contacting colonies and (2) it shows the power of simple experiments and quantitative microscopy (8/9)

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Amir Mitchell @amitchell.bsky.social · Dec 2

Careful quantification revealed that the damage decay curves are identical in contacting and non-contacting colonies. Therefore, direct contact is not only not required, but it doesn’t even increase the level of toxicity beyond what is expected by proximity (7/9)

Traces of DNA-damage reporter decay with distance from colibactin producers

Amir Mitchell @amitchell.bsky.social · Dec 2

Next, we monitored colibactin damage in separated colonies. This setup allowed us not only to validate contact independence, but also to accurately quantify how DNA-damage decays across distance (6/9)

Experiment setup for monitoring colibactin induced DNA damage in neighboring colonies.

Amir Mitchell @amitchell.bsky.social · Dec 2

Microscopy imaging revealed that DNA damage is observed even hundreds of microns (YFP halo) away from the secreter front (mCherry) suggesting that direct cell-cell is not needed for toxicity (5/9)

Diagram of experiment setup. Colony of a colibactin producing cell is placed on a lawn of DNA-damage reporter cells. The yellow halo around the colony marks DNA damage

Amir Mitchell @amitchell.bsky.social · Dec 2

We cloned a YFP DNA-damage reporter in E. coli and tested how far colibactin induced damage “travels” across a lawn of cells (we tagged secreters and responders with constitutive mCherry and CFP to tell them apart) (4/9)

Diagram showing the plasmids used for cloning the colibactin producing strain and the DNA-damage reporter strain

Amir Mitchell @amitchell.bsky.social · Dec 2

Colibactin mode of delivery is still under debate, with common models claiming delivery requires direct cell-cell contact. While contact certainly improves toxicity (see great recent work by the Lars Vereecke lab), does it add anything beyond what is expected by proximity alone? (3/9)

Amir Mitchell @amitchell.bsky.social · Dec 2

Colibactin is deeply studied in human cells due to its involvement in colorectal cancers, yet far less is known in the context of microbial communities. Our first study with @daganlab.bsky.social revealed self-inflicted DNA-damage in colibactin producers (2/9)
genome.cshlp.org/content/earl...

Colibactin leads to a bacteria-specific mutation pattern and self-inflicted DNA damage

An international, peer-reviewed genome sciences journal featuring outstanding original research that offers novel insights into the biology of all organisms

genome.cshlp.org

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