iiinova — where your digital self keeps evolving

Jeff Mugridge @jeffmugridge.bsky.social · 09/07/2026

As the lab graduates more PhDs, I'm really feeling just how painful it is to constantly be losing your most senior people! 😭 (that's the goal of course! But it's still tough to always be sending off your best folks who've built up deep expertise on projects and techniques!)

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Jeff Mugridge @jeffmugridge.bsky.social · 29/06/2026

💥 Final version of our Elp3 paper is now live @natcomms.nature.com! We show how the radical SAM enzyme Elp3 uses a molecular tunnel to transport acetate molecules and modify tRNA! We think our proposed mechanism answers long-standing questions about how this important enzyme works! rdcu.be/fq2bw

rdcu.be

Elp3 uses a conserved molecular tunnel to transport acetate between distant active sites and catalyze tRNA wobble base modification

Nature Communications - tRNA modifications are essential for accurate translation, but how Elp3 catalyses them across distant active sites was unclear. Here, the authors show that Elp3 uses a...

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Jeff Mugridge @jeffmugridge.bsky.social · 08/11/2025

Thanks for hosting me! Really fun visit to UMBC and heard about lots of great science!

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Stand Up for Science! @standupforscience.net · 16/09/2025

DUCK AROUND, FIND OUT! With our duck delivery in tow, we waddled up to the Hill to let our representatives know that it's time to send the Quack-In-Chief packing. #ImpeachRFK

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Scott Delaney @scott-delaney.bsky.social · 16/06/2025

THIS IS IT! THIS IS HUGE!! PLAINTIFF'S WIN!! Judge Young rules that the NIH grant terminations at issue in these cases are illegal and therefore vacated. BOOM!

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Jeff Mugridge @jeffmugridge.bsky.social · 14/06/2025

LOTS of people and LOTS of energy for #NoKings in Newark DE! ❌👑❌ @indivisiblenewark.bsky.social

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Jenna Norton @jenna-m-norton.bsky.social · 10/06/2025

Please sign on and add your voice in calling for an NIH that prioritizes the safety of research participants and public health over political momentum. actionnetwork.org/forms/add-na...

actionnetwork.org

ADD YOUR NAME: Sign the Open Letter in Support of NIH Staff

Join the courageous and committed National Institutes of Health (NIH) public servants by adding your name now.

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Jeff Mugridge @jeffmugridge.bsky.social · 04/06/2025

My favorite is the 'world tour' tee shirt 🤣🤣 Looking forward to this GRC!

Bioorganic GRC 'world tour' shirt -- repeats Andover, NH over and over.

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Rachel W. Martin @rwmartin.bsky.social · 10/05/2025

Without basic science, there is nothing to translate.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

As far as we know, this is only the ~2nd example of a molecular tunnel connecting active sites in radical SAM enzymes, and the 1st example of acetate transport in an enzyme! We're working on more pieces of this puzzle to show how Elp3/Elongator tRNA modification is regulated! Congrats Evan! 9/9

Evan's PhD graduation sword says 'Tamer of Elp3'.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

See lots more experiments in the paper, but we propose a new model for Elp3/Elongator tRNA modification where Elp3 hydrolyzes acteyl-CoA to release acetate into the molecular tunnel which transports it to the RS active site for radical chemistry and tRNA modification! 8/9

Figure from the paper showing steps of the proposed Elp3 tRNA modification mechanism. Acetyl-CoA is hydrolyzed by the KAT domain to release acetate (or acetic acid) into the molecular tunnel. Acetate diffuses through the tunnel to the RS active site, where conserved residues position acetate for canonical radical SAM chemistry to generate a reactive acetate-based radical. The acetate radical reacts with tRNA to form the wobble base cm5U modification.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

Evan next showed that if you *block* the molecular tunnel by mutating a tunnel-lining residue to Trp, you cripple tRNA modification activity without affecting tRNA binding or acetyl-CoA binding and turnover much. 7/9

Figure from the paper with structural models showing how Trp mutation blocks the molecular tunnel (A), and that mutation completely destroys enzyme activity (B), but not tRNA binding to Elp3 (C), or acetyl-CoA hydrolysis (D).

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

With active Elp3, now we can do some enzymology! To test our acetate hypothesis, Evan showed that if you do Elp3 tRNA modification reactions where you *leave out* acetyl-CoA, but give the enzyme acetate, it still works! 6/9

Graph of kinetic data showing that Elp3 is active with acetyl-CoA, but inactive with -Elp3 or -SAM controls. If you leave out acetyl-CoA, but add acetate, you still get tRNA modification. We also did MS to show you're actually making cm5U in all of these cases.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

Let's test that! ONE PROBLEM: Elp3 is notoriously difficult to work with because its [4Fe-4S] cluster is very air sensitive. BUT after lots of work in our glovebox, grad student Evan Geissler was able to reconstitute in vitro Elp3 tRNA modification activity for the first time in over a decade!! 5/9

media.tenor.com

a room with a sign that says exit and a gifbin.com logo in the corner

Alt: animated GIF showing a scientist giving high fives to the gloves on an air-free glovebox. Evan was happy too when he got Elp3 activity!

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

When we looked closely at structures of recent Elongator-tRNA complexes, we found when tRNA binds Elp3 it creates an enclosed *molecular tunnel* that connects the acetyl-CoA binding site and radical SAM active site of Elp3! Could the enzyme use the tunnel to transport *acetate* to make cm5U? 4/9

We discovered that previously determined Elp3-tRNA structures have an enclosed molecular tunnel (pink) that connects the Elp3 acetyl-CoA binding site (light green KAT domain) with the Elp3 radical SAM active site (teal RS domain) where modification chemistry happens. This image shows the protein structure of an Elp1,2,3-tRNA complex, zoomed in on the Elp3-tRNA interaface that generates the molecular tunnel using the surface of Elp3 and tRNA.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

...in all the Elp3 and Elongator structures that have been determined, the acetyl-CoA binding site is over 20 A away from the radical SAM site where the modification chemistry happens! How does acetyl-CoA or its acetyl group get all the way across the enzyme? 3/9

Surface of Elp3 enzyme showing a 23 A gap between the acetyl-CoA binding site on the KAT domain and the radical SAM active site on the RS domain. How do the acetyl groups get from one side of the enzyme to the other?

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

Elp3, which in eukaryotes functions as part of the Elongator complex, installs the really important intermediate modification cm5U on the wobble base of tRNAs. The cm5U carbon and oxygen atoms (in red) come from cofactor acetyl-CoA. BUT... 2/9

chemical structure of the 5-carboxymethyluridine (cm5U) modification. It's an important intermediate modification that gets further elaborated in the cell to make a family of tRNA modifications that are important for translation.

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Jeff Mugridge @jeffmugridge.bsky.social · 08/05/2025

💥Latest preprint from our lab is now live! We propose a crazy(!?) new mechanism for how the radical SAM enzyme Elp3 (a subunit of the Elongator complex) modifies tRNA! #RNAsky #enzymes 🧵...

Graphical abstract shows molecules of acetate traveling through a molecular tunnel in Elp3 that connects its distant active sites

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Jordan Meier @doc-jlmeier.bsky.social · 10/04/2025

Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost. www.training.nih.gov/research-tra...

training.nih.gov

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Stand Up for Science! @standupforscience.net · 08/04/2025

📣 GET IN, DORKS! We are going protesting...AGAIN! 📣 This time we are standing up for our core value of academic freedom and asking university leadership to STAND UP WITH US against Trump's attack on higher ed ✊ #StandUpWithUS Register/find an event: actionnetwork.org/event_campai...

NATIONWIDE CAMPUS ACTION
STAND UP WITH US
because science, higher ed, and democracy are for everyone.
Where: YOUR COLLEGE CAMPUS
When: YOUR LAST DAY OF CLASSES
StandUpForScience2025.org

It’s time for a Summer Send-Off

Stand Up, Fight Back - TOGETHER!

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Max Kozlov @maxkozlov.bsky.social · 04/04/2025

🚨 BIG week for lawsuits against the NIH. Now 16 states have sued NIH and HHS for "engag[ing] in a concerted, and multi-pronged effort to disrupt NIH’s grants." "The result of these disruptions has been, in a word, devastating," they write. ag.ny.gov/press-releas...

ag.ny.gov

Attorney General James Sues Trump Administration for Illegally Cutting Funding for Medical Research

NEW YORK – New York Attorney General Letitia James and a coalition of 15 other attorneys general today filed a lawsuit against the Trump administration for its

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SmithLabUMBC @smithlabumbc.bsky.social · 28/03/2025

Our 28-yr U-RISE/MARC NIH grant that has served over 500 students and made us one of the top institutions producing African American students who go on to receive MD/PhDs in the United States was just cancelled yesterday. What a unnecessary and tragic end to such an impactful program...

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Joshua Weitz @joshuasweitz.bsky.social · 28/03/2025

Working with an interdisciplinary team, we have developed a website to communicate how the White House's proposed cuts to health research would cause losses of $16B and 68,500 jobs. Find out how your community may be impacted. Explore more at SCIMaP: scienceimpacts.org a 🧵

US map via scienceimpacts.org visualization of economic loss due to IDC cuts to 15% as part of Feb 7, 2025 executive order, with shading denoting intensity of cuts.

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Philip Gourevitch @pgourevitch.bsky.social · 19/03/2025

powerful detailed account of ICE captivity "To put things into perspective: I had a Canadian passport, lawyers, resources, media attention, friends, family and even politicians advocating for me...Imagine what this system is like for every other person in there" www.theguardian.com/us-news/2025...

theguardian.com

I’m the Canadian who was detained by Ice for two weeks. It felt like I had been kidnapped

I was stuck in a freezing cell without explanation despite eventually having lawyers and media attention. Yet, compared with others, I was lucky

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Jeff Mugridge @jeffmugridge.bsky.social · 15/03/2025

Me, leaving the US for a conference in Europe.

A smiling plan, flying away while bombs explode everywhere

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Jeff Mugridge @jeffmugridge.bsky.social · 11/03/2025

Yes! We do this for all the PhD students who graduate from our lab. Let me know if you want the name of my sword guy! 🗡️🧙‍♂️

Custom inscription with PhD student name, graduation date, fancy title, and thesis-defining protein structure

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Jeff Mugridge @jeffmugridge.bsky.social · 07/03/2025

Francis Collins brings down the house! 🎸🎸🎸

Former NIH director Francis Collins playing the guitar and signing a song at the stand up for science rally

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Jeff Mugridge @jeffmugridge.bsky.social · 07/03/2025

Great crowd and a great time at #StandUpForScience DC today at the Lincoln Memorial! @standupforscience.bsky.social Photos… 🧵

Some colleagues at the beginning the rally, with our signs in front of the Lincoln Memorial

Lots of people standing up for science in front of the Lincoln Memorial

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CantlonLab @cantlonlab.bsky.social · 07/03/2025

Write for @sciencehomecoming.bsky.social A major property of communication is that only repeated messages stick. Even if there’s already an op-ed on science funding in your town, adding more makes an impact. After we @standupforscience.bsky.social today, let’s write to bring it home. 🧪🏠

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Jeff Mugridge @jeffmugridge.bsky.social · 04/03/2025

Yes, that'd be great, thanks Vince!

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Jeff Mugridge @jeffmugridge.bsky.social · 04/03/2025

Anyone have tips for making active homemade Phusion polymerase? We have a plasmid (no his tag), and are doing purification by heat denaturation and then sizing, from which we get *a lot* of purified protein. But we can't see any polymerase activity from these purified preps!

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Jeff Mugridge @jeffmugridge.bsky.social · 03/03/2025

Let's go! Looking like a great Friday in DC! I'll be there!

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Science Homecoming @sciencehomecoming.bsky.social · 27/02/2025

Happy Homecoming to Biochemistry Professor and High School Science Olympian Jeff Mugridge from Central New York who wrote for The Post Standard about the rewards of science funding for NY health and economy 🍎 🧪🧬🔬🏠@jeffmugridge.bsky.social www.syracuse.com/opinion/2025...

syracuse.com

Protect science funding driving innovation, investment in Syracuse (Guest Opinion by Jeffrey Mugridge)

Severe cuts to budgets and staff threaten to undermine the next generation of American scientists, writes professor who discovered his love of science as a Liverpool High student.

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Jeff Mugridge @jeffmugridge.bsky.social · 27/02/2025

I wrote an opinion piece for my hometown newspaper in Central NY about attacks on NIH/NSF/research and why this harms not just US science but local jobs and economies. Thanks @sciencehomecoming.bsky.social for sparking these efforts! I encourage others to join in! www.syracuse.com/opinion/2025...

syracuse.com

Protect science funding driving innovation, investment in Syracuse (Guest Opinion by Jeffrey Mugridge)

Severe cuts to budgets and staff threaten to undermine the next generation of American scientists, writes professor who discovered his love of science as a Liverpool High student.

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Senator Lisa Blunt Rochester @bluntrochester.senate.gov · 21/02/2025

These NIH funding cuts threaten research happening in Delaware on heart disease, cancer, diabetes, stroke recovery, & more. This is what this administration is focused on. Not lowering your household costs.

delawarebusinesstimes.com

Delaware’s innovation pipeline could be at risk with new NIH funding policy

With a proposed cap on indirect costs for NIH grants, Delaware's life science sector could be hit the next generation of start-ups and researchers.

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Scott Delaney @scott-delaney.bsky.social · 21/02/2025

NIH indirects case update: Hearing ongoing now, and I'll try to live tweet some notable exchanges. Prior to more detailed arguments, Judge Kelley starts off with a few point questions to both sides: (I'm paraphrasing here)

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