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Jeff Mugridge

@jeffmugridge.bsky.social

630 followers 570 following 93 posts

I'm a scientist! Asst Prof at Univ of Delaware | RNA biochemistry, RNA modifications, (metallo)enzymology, structural biology, and chemistry | Postdoc at UCSF | PhD at UCBerkeley | he/him mugridgelab.org

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Jeff Mugridge @jeffmugridge.bsky.social · May 8

💥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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Reposted by Jeff Mugridge

Stand Up for Science! @standupforscience.bsky.social · 22d

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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Reposted by Jeff Mugridge

Scott Delaney @scott-delaney.bsky.social · Jun 16

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!

Scott Delaney @scott-delaney.bsky.social · Jun 16

"This Court rules that the challenged directives . . . are arbitrary and capricious."

"They are of no force and effect."

"They are illegal and so are each of the terminations before this Court"

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Reposted by Jeff Mugridge

Gregg Gonsalves @gregggonsalves.bsky.social · Jun 14

We are just getting started. “American Spring? How nonviolent protest in the US is accelerating…” wagingnonviolence.org/2025/06/amer...

American Spring? How nonviolent protest in the US is accelerating

Contrary to conventional wisdom, anti-Trump protests this year have dwarfed 2017 in size, and they have been extraordinarily peaceful.

wagingnonviolence.org

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Jeff Mugridge @jeffmugridge.bsky.social · Jun 14

LOTS of people and LOTS of energy for #NoKings in Newark DE! ❌👑❌

@indivisiblenewark.bsky.social

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Reposted by Jeff Mugridge

Jenna Norton @jenna-m-norton.bsky.social · Jun 10

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...

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.

actionnetwork.org

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Jeff Mugridge @jeffmugridge.bsky.social · Jun 4

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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Jeff Mugridge @jeffmugridge.bsky.social · May 31

Thanks John!

Reposted by Jeff Mugridge

Rachel W. Martin @rwmartin.bsky.social · May 10

Without basic science, there is nothing to translate.

K.T. Elliott @ktelliottmicro.bsky.social · May 9

I know you all know this, but apparently it needs to be said that basic science is a NECESSARY PRECURSOR to translational science

Dustin Rubenstein @dustinrubenstein.com · May 9

NSF to ONLY fund research in five areas: artificial intelligence, quantum information science, biotechnology, nuclear energy, and translational science. Can this be happening?

www.science.org/content/arti...

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Jeff Mugridge @jeffmugridge.bsky.social · May 8

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'.

Jeff Mugridge @jeffmugridge.bsky.social · May 8

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 · May 8

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 · May 8

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 · May 8

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

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!

media.tenor.com

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Jeff Mugridge @jeffmugridge.bsky.social · May 8

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 · May 8

...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?

Jeff Mugridge @jeffmugridge.bsky.social · May 8

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 · May 8

💥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 🧵...

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Jeff Mugridge @jeffmugridge.bsky.social · May 2

😬😬

Dan Garisto @dangaristo.bsky.social · May 1

BREAKING: NSF has frozen all grant funding, as of yesterday. It's unclear when they will resume funding awards, or why the pause has been put in place. www.nature.com/articles/d41...

Exclusive: NSF stops awarding new grants and funding existing ones

US science funder also plans to screen grant applications for compliance with ‘agency priorities’.

www.nature.com

Jeff Mugridge @jeffmugridge.bsky.social · Apr 23

Tucson!🌵 #desert #photography

View with cactus of Tucson and the Santa Catalina mountains

Symmetrical view of a saguaro cactus arm

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Reposted by Jeff Mugridge

Jordan Meier @doc-jlmeier.bsky.social · Apr 10

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...

www.training.nih.gov

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Jeff Mugridge @jeffmugridge.bsky.social · Apr 14

Well done.

Malinda Lo @malindalo.bsky.social · Apr 14

Harvard redid its whole homepage to push back against the administration’s demands. I mean, this is just a website but I think it’s kind of a great PR move: www.harvard.edu

Harvard University

Harvard University is devoted to excellence in teaching, learning, and research, and to developing leaders who make a difference globally.

www.harvard.edu

Jeff Mugridge @jeffmugridge.bsky.social · Apr 9

Yes, thanks to @aaup.bsky.social and others!

Nathan Kalman-Lamb @nkalamb.bsky.social · Apr 9

10 national unions repping 3 million members demand the release of abducted immigrant workers and call for employers and university admins to refuse to cooperate and elected officials to “find their spines.”

This is the way.

labornotes.org/blogs/2025/0...

Ten national unions and dozens of locals representing more than 3 million members have issued a joint statement demanding the release of immigrant workers recently snatched by Immigration and Customs Enforcement.

The statement names farmworker union leader Alfredo “Lelo” Juarez, who was picked up in what appears to be blatant retaliation for his organizing; SEIU Local 925 member Lewelyn Dixon, a University of Washington lab technician detained on her way home from visiting family; SEIU Local 509 member Rumeysa Ozturk, a graduate student whose detention by federal agents was captured in chilling footage; sheet metal worker Kilmar Armando Abrego Garcia, a SMART Local 100 apprentice who was sent to El Salvador’s notorious prison complex; and United Auto Workers Local 2710 member Mahmoud Khalil, abducted by federal agents in front of his eight-months-pregnant wife.

The unions are also calling on employers, university administrators, and local governments to refuse to cooperate—and demanding that elected officials “find their spines.”

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Reposted by Jeff Mugridge

Stand Up for Science! @standupforscience.bsky.social · Apr 8

📣 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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Reposted by Jeff Mugridge

Max Kozlov @maxkozlov.bsky.social · Apr 4

🚨 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...

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

ag.ny.gov

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Reposted by Jeff Mugridge

SmithLabUMBC @smithlabumbc.bsky.social · Mar 28

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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