Jeff Mugridge

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

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

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!

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.

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

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

@indivisiblenewark.bsky.social

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.

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...

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

Thanks John!

Without basic science, there is nothing to translate.

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

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

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.

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 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).

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

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.

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

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!

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

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.

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

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?

...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

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.

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

💥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 🧵...

😬😬

View with cactus of Tucson and the Santa Catalina mountains

Symmetrical view of a saguaro cactus arm

Another purplish cactus

Cactus with yellow flowers

Tucson!🌵 #desert #photography

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...

Well done.

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

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!

📣 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...

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

🚨 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...

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...

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.

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 🧵

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

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...

A smiling plan, flying away while bombs explode everywhere

Me, leaving the US for a conference in Europe.

Medieval Swords and Tankards Strongblade is a manufacturer and retailer of swords, and tankards. We specialize in custom engraved swords and tankards.

Roger at strongblade.com is a WIZARD with custom sword inscriptions!