iiinova — where your digital self keeps evolving

PlessLab @plesslab.bsky.social · 28/08/2026

This one took patience: many oocytes, lots of peptide, and a lot of persistence - big thanks to @lauriepeverini.bsky.social and the whole team for keeping at it. Gratefully funded by the @lundbeckfonden.bsky.social and the EU's Marie Skłodowska-Curie Actions. 4/x

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PlessLab @plesslab.bsky.social · 28/08/2026

It works and the signal tracks inactivation (both fast and steady-state) rather than activation. And two things binding at distant sites, the auxiliary protein iFGF12A at the C-terminus and lidocaine in the pore, both allosterically tune the kinetics of the DIII–DIV linker movements. 3/x

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PlessLab @plesslab.bsky.social · 28/08/2026

In our new preprint we placed a bright, photostable rhodamine in the intracellular domain of the human Nav1.5, next to the IFM motif, by having a living cell splice in a chemically synthesized 77-mer peptide via two orthogonal split inteins. 2/x

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PlessLab @plesslab.bsky.social · 28/08/2026

Voltage-clamp fluorometry turns 30 this year - thank you, Isacoff & Bezanilla! It has been a great tool to watch the outside of channels move, but of less use on the inside. That’s a shame because that is where a lot happens, incl. conformational changes related to sodium channel inactivation. 1/x

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PlessLab @plesslab.bsky.social · 08/04/2026

One week left to apply for the EMBO/FEBS lecture course on #ionchannels and #transporters in beautiful Erice in May 2026: meetings.embo.org/event/26-ion... Please share

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PlessLab @plesslab.bsky.social · 16/01/2026

Time to sign up! Registration for the joint FEBS/EMBO course on ion channels and transporters in Erice, Italy (May 13-19th 2026) is now open: meetings.embo.org/event/26-ion... Please share and repost.

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PlessLab @plesslab.bsky.social · 26/11/2025

To all trainees interested in channels and transporters: the joint FEBS/EMBO course will go ahead in Erice, Italy from May 13-19 2026: network.febs.org/posts/new-jo... Further details to come soon. Please share and repost.

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PlessLab @plesslab.bsky.social · 17/09/2025

Collaborator @amelierocks.bsky.social complemented this with predictions of protein stability and conservation scores. In combination with functional work this establishes a framework for classifying suspected disease variants, which we hope will aid assessment of NALCN variant pathogenicity

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PlessLab @plesslab.bsky.social · 17/09/2025

@chowhanchua.bsky.social implemented use of a combination of multiple parameters derived from two-electrode voltage-clamp electrophysiology recordings. These allow us to classify LoF and GoF phenotypes and to provide mechanistic insight into the molecular mechanism underlying specific variants.

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PlessLab @plesslab.bsky.social · 17/09/2025

De novo and inherited NALCN variants can lead to severe developmental syndromes. Although variants of uncertain significance or presumed pathogenic variants have been studied in heterologous systems before, there is no generally accepted framework on how to assess or predict variant pathogenicity.

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PlessLab @plesslab.bsky.social · 17/09/2025

After years in making, I am glad to be able to share our attempt on establishing a framework for combined functional and computational assessment of variant pathogenicity in the sodium leak channel NALCN: www.biorxiv.org/content/10.1...

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PlessLab @plesslab.bsky.social · 22/08/2025

Wonderful visit to beautiful Bergen, Norway. Big thanks to @herculeria.bsky.social for hosting and to Tim Lynagh for guiding me up the local hills

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PlessLab @plesslab.bsky.social · 06/07/2025

“It’s the company that matters!” This is certainly true for acid-sensing ion channel 1a, whose function is modulated by the presence of monocarboxylate transporter 1 All was made possible by the drive & curiosity of the fantastic @mette-h-poulsen.bsky.social www.biorxiv.org/cgi/content/...

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PlessLab @plesslab.bsky.social · 14/03/2025

Our latest paper on the sodium leak channel NALCN complex is now online. We found that the neuronal SNARE proteins syntaxin 1A and SNAP25 inhibit sodium leak currents both in heterologous systems and in neurons! www.science.org/doi/10.1126/...

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PlessLab @plesslab.bsky.social · 13/12/2024

...and outlines how mutations in the pre-M1 / re-entrant loop can shift the conformational equilibrium between closed and open states.

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PlessLab @plesslab.bsky.social · 13/12/2024

Using a combination of structures, ephys and VCF, we demonstrate that the mechanism of channel activation by protons differs from that by peptide toxins...

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PlessLab @plesslab.bsky.social · 13/12/2024

Grateful for having contributed to this work by the Isabelle Baconguis group, who solved eleven (!) new structures of hASIC1a to show that open states require linear transmembrane helices, while desensitized states display a dazzling structural diversity www.biorxiv.org/content/10.1... #ionchannels

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PlessLab @plesslab.bsky.social · 16/11/2024

First post here: just returned from an inspiring trip to meet colleagues and collaborators at Genentech, UC Davis and UW Seattle - big thanks to the wonderful hosts!

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