Congrats Deepshi, Teresa, and the whole team! 🎉🪱✨️

... this is a reference to William Kaelin's essay: Publish houses of brick, not mansions of straw.

This is such a great resource! Thanks Jordan and the whole team! ✨️🪱

Thank you. I am so happy you like it!

Joy Alcedo, Cori Bargmann, Rita Droste, @wormsense.bsky.social , Josh Kaplan, Takaaki Hirotsu, Bob Horvitz, Ikue Mori, Junho Lee, Roger Pocock, @dougp.bsky.social, and Shawn Xu kindly provided >25 C. elegans strains, and the CGC 30 more!

Wormbase and @wormatlas.bsky.social were indispensable. 28/

We had rigorous and insightful discussions with Max Heiman @heiman.bsky.social, Steven Cook @dumpyunc.bsky.social, and Oliver Hobert, about the anatomy of the amphids/labial organs and the pharyngeal nervous system; especially which neurons truly sense the outside of the worm, and which do not. 27/

At the 2023 Worm Meeting, Alexander Gottschalk tracked down our poster and told us about his lab’s amazing structural modeling of LITE-1 and GUR-3. That insight was critical, it helped us to think much more biophysically about how neurons sense H2O2. 26/

We have lots of people to thank, especially Nikhil Bhatla, Steven Sando, and Bob Horvitz. Their exquisite foundational work showed how H2O2 and UV inhibit feeding and promote spitting via PRDX-2/LITE-1/GUR-3, and they were incredibly generous with ideas that helped move this project forward. 25/

Going forward, it will be interesting to determine whether circuit defects in aging and neurodegenerative disease arise from changes in H2O2 signaling via peroxiredoxins rather than from direct oxidative damage. 24/

In this view, cytosolic peroxiredoxins transduce information carried by non-cytotoxic levels of H2O2 into long-range electrical signals that can modulate behavior and distant physiology. 23/

Because cells routinely produce non-cytotoxic H2O2 as a metabolic byproduct (and because H2O2 can diffuse hundreds of microns and cross membranes), our study leads us to propose that peroxiredoxins enable H2O2 to play a much broader role in regulating neuronal activity than previously thought. 22/

In contrast, our studies in C. elegans show that H2O2 can quickly modulate neuronal activity at much lower concentrations (even 1 µM!), through a process enabled by cytosolic peroxiredoxins. 21/

H2O2 is traditionally thought as a cytotoxic oxidant: at ~0.25-1 mM (reported during inflammation and post-ischemic reperfusion), it rapidly reacts with proteins, nucleic acids, and lipids, causing dysfunction that may increase the aging brain’s vulnerability to neurodegenerative disease.

But! 20/