@rubenlgonzalez
Dean of Science, Professor of Chemistry, and Professor of Physiology & Cellular Biophysics at Columbia University | Single-Molecule Biophysics, Structural Biology, and Biochemistry | Diversity, Equity, and Inclusion in STEM
C.S. Wu changed physics with the Wu Experiment, proving nature distinguishes left from right—parity isn’t conserved. Although others won the 1957 Nobel, she was excluded. A champion of equity in STEM, her legacy lives on
at Columbia Physics with this year’s lecturer, Nathalie P. de Leon.
Tons of fun at the first @columbiacollege.bsky.social Fac’ to Table Lunch at John Jay, hosted by the one and only Dean Josef Sorett!
So great to be in community with our amazing students and just talk about what’s on their minds: history, jazz, Frontiers of Science, teaching, and DJ’ing! IYKYK!
Dozens of researchers will move to France from US following high-profile bid to lure talent
Large proportion worked at Columbia University, which had its grants cut and frozen by the administration of US President Donald Trump.
www.nature.com/articles/d41...
I agree, Da-Neng—it’s been great fun working together and I can’t wait to see what we’ll learn next from our ongoing transporter studies!
Huge congrats to Colin Kinz-Thompson, Marisa Lopez-Redondo, @chrismulligan.bsky.social, @davidbsauer.bsky.social, and the rest of the team from my lab and the labs of @danengw.bsky.social, Joe Mindell, David Stokes, John Hunt, and Emad Tajkhorshid.
Grateful for the science and the superb teamwork!
The big surprise: Transporter dynamics are largely substrate-independent!
Thermodynamic modeling shows cooperative co-substrate binding, rather than motion inhibition, minimizes slippage, offering a general strategy for efficient energy transduction in secondary transporters.
Our data directly reveal elevator-type motions that are...
• stochastic and fast
• independent between protomers
• repeated many times before productive transport
Yet transport remains tightly coupled via highly cooperative co-substrate binding, not by suppressing motion.
(Top) smFRET enables direct observation of a sodium-coupled transporter executing rapid, stochastic elevator-type motions in lipid bilayers. (Bottom) Thermodynamic modeling shows how highly cooperative co-substrate binding enables tightly coupled transport, without suppressing these motions.
New work out today in PNAS!
Secondary active transporters are everywhere, but direct observation of their structural dynamics is rarely achieved.
Here, we capture the real-time dynamics of a sodium-coupled dicarboxylate transporter using smFRET.
🧵⬇️
doi.org/10.1073/pnas...
eIF3 is a central player in translation initiation and has been implicated in events throughout translation.
New Biochem Soc Trans review:
eIF3 as a modular, central regulator of translation.
Authored by @nickide.bsky.social and Colin Echeverría Aitken, this review integrates genetic, biochemical, and structural perspectives and highlights open mechanistic questions.
doi.org/10.1042/BST2...
Huge shout-out to the fantastic team of researchers and authors who worked on this: Nina Michael*, Bridget Huang*, @korakray.bsky.social, and Colin Kinz-Thompson!
(*equal contribution)
Using a loss-of-function ArfA mutant, we show that the role of wild-type ArfA is not to recruit RF2, but to shape the conformational energy landscape of the ribosome to bias RF2 away from transient binding intermediates and toward the hydrolysis-competent docked state.
RF2 doesn’t just switch between 'collapsed' and 'extended' states.
We directly observe multiple transient intermediate conformations that control RF2 binding, docking into the peptidyl transfer center, and dissociation.
Energy-landscape model of RF2 activation. Comparison of termination complexes (TC), wild-type ArfA-bound nonstop elongation complexes (nsECs), and loss-of-function ArfA mutant-bound nsECs reveals that wild-type ArfA promotes RF2 docking to nsECs by reshaping the conformational cascade.
Slightly overdue article highlight!
In PNAS, we use smFRET to reveal how polypeptide release factor 2 (RF2) undergoes a cascade of structural changes to catalyze polypeptide release during translation termination and ArfA-mediated ribosome rescue.
🧵⬇️
doi.org/10.1073/pnas...
In the absence of m¹G37, we directly visualize the formation of four, and even five, codon-anticodon base pairs on the ribosome, thereby capturing a long-standing hypothesis for +1 frameshifting.
I’ve been behind on highlighting a few recent papers—more posts coming soon.
Mechanistic model for +1 frameshifting suppression. The m¹G37 tRNA modification blocks expanded codon–anticodon interactions, preserving translational fidelity.
A (belated!) highlight from an excellent collaboration with
@dunhamlab.bsky.social and #HouLabTJU.
In this Nat Commun paper, we combine smFRET and cryo-EM to show how the tRNA modification m¹G37 stabilizes the reading frame—and what happens when it’s missing.
The Gonzalez Lab at Columbia University is seeking a scientific leader!
Join us in a Research Scientist position, driving single-molecule, structural, and biochemical studies of translation, translational control, and other RNA-based processes.
Apply: apply.interfolio.com/176949
Our findings reveal a general mechanism of biomolecular stability--compensatory flexibility--that we predict is widely used by structured biopolymers. This conceptual breakthrough allows the design of mutations and ligands that can disrupt or engineer biomolecular function. 5/5
We found that the stem-loop folds via two distinct pathways, each defined by a different loop structure.
By tuning its flexibility, the RNA can favor either rapid folding or resistance to unfolding—an adaptive strategy for robust structural stability. 4/5
Using a carbon nanotube–based single-molecule field-effect transistor (smFET), we recorded the folding and unfolding of an individual UUCG stem-loop at microsecond time resolution, revealing conformations and kinetic pathways that ensemble methods cannot resolve. 3/5
An excellent collaboration with the labs of Ken Shepard and Colin Nuckolls, led by @ssjang.bsky.social, @korakray.bsky.social, and David Lynall! 2/5
New from our lab in @narjournal.bsky.social:
We dissect the folding dynamics of a fundamental element of RNA secondary structure—a stem-loop—at single-molecule and microsecond resolution.
doi.org/10.1093/nar/... 1/5
Over 60 NIH staff are blowing the whistle on Trump’s assault on biomedical research — calling it unethical, illegal, and dangerous. Grants canceled. Trials halted. Science censored. This is a direct threat to public health. www.standupforscience.net/bethesda-dec...
A Puerto Rican Ph.D. student. A first-gen scientist. Both lost NIH grants under vague “new priorities.”
Nearly 2,500 projects and $1.6B in cut or stalled grants.
No vote. No debate. Just science erased. www.nytimes.com/interactive/...
“If things continue as they are, American science is ruined.”
This isn’t sabotage from the outside — it’s self-inflicted. Cuts to research, visa bans, and closed doors to global talent are doing what an enemy of the US could only dream of. www.nytimes.com/2025/05/31/w...
I said I would! 🤣
Check out group member Meghna Maiti’s poster at #RNA2025! She’s presenting new findings on how frameshift-suppressor tRNAs exhibit altered dynamics in the ribosomal A site that modulate translocation and +1 frameshifting. Friday, 8–10 PM PT — she’s at P2-492!
Photo credit: Pallav Kosuri by way of Jingyi Fei.
A blast from the past! The Gonzalez Group, circa 2008, celebrating our first publication! Check out much, much younger versions of, from left to right, Pallav Kosuri, yours truly, Sam Sternberg, Mike Englander, @jingyifei.bsky.social, Daniel MacDougall, Margaret Elvekrog, and Subasree Das!
Excited to share that group member Riley Gentry will present a talk at #RNA2025 tomorrow! He’ll reveal how PIC-bound eIFs collaborate to drive mRNA loading during translation initiation. Don’t miss “The mechanism of mRNA activation” at 9 AM in the Translation Mechanisms plenary.
“Undermining the future of American science is not a path to accountability — it’s a path to decline.”
In a powerful new piece, my colleague Daphna Shohamy explains how canceled grants are driving young scientists out of science—and out of the country.
🔗 www.statnews.com/2025/05/07/u...
This op-ed details how the billionaires now destroying basic science at our universities built their fortunes on its breakthroughs. They're aggressively moving to deny others the very foundation that made their own successes possible. www.nytimes.com/2025/04/28/o...