Fondation Maladies Rares

Modeling disease-causing mutations of Neurobeachin/NBEA in the nematode Caenorhabditis elegans


We are grateful to the Fondation Maladies Rares that will support our study of variants of unknown significance of Neurobeachin / NBEA. This funding will allow us to create new tools in the model nematode C. elegans to evaluate the impact of mutations causing this very rare disease associated with strong neurodevelopmental deficits and epilepsy (Mulhern et al., 2018).

We hope that this work will contribute to the diagnosis of patients with novel variants in Neurobeachin in the future in order to better define the phenotypic spectrum of this "disease" (not named officially yet).

New team photo

July 2019

A big thank you to Léa, Charlotte, Emilie (no pictured), and Quentin who have been wonderful rotation students this year. They have each pioneered new projects in which we model genetic variant for human diseases in C. elegans.

Missing from the picture: Caroline Borkowski.

NIH Undiagnosed Diseases Network

Functional evaluation of Neurobeachin/NBEA genetic variants in the model nematode Caenorhabditis elegans


Today on #RareDiseaseDay we submit our 1st application to the NIH's Undiagnosed Diseases Network "Gene Function Studies" call. It flows directly from ERC-funded blue-sky research. We hope that it will get funded so we can demonstrate (once more...) how basic non-applied "worm research" leads directly to Rare Disease model systems!


Despite very encouraging and positive comments, our proposal was not funded by UDN. We'll keep working on it and try again next year.

Newest paper out today!


“Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels”

Great collaboration between our group, IPMC Nice's Delphine Bichet and Florian Lesage and Dawon Kang at Gyeongsang National University.

Editor's Summary: "Mutations that modulate the activity of ion channels are essential tools to understand the biophysical determinants that control their gating. Here authors reveal the role played by a single residue in the second transmembrane domain of vertebrate and invertebrate two-pore domain potassium channels."

Indeed, we found that “Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels”. We named this position TM2.6.

We think this works by increasing K2P channel open probability (first found serendipitously for ORK1 by Ben-Abu, Zhou, Zilberberg and Yifrach in 2009, and by Chatelain et al. and @ProfKalium (S. Tucker) for TWIK1 and THIK channels)

It got better, when we saw that we could tune the effect of these gain-of-function mutants by using different amino acid substitutions.

Using CRISPR/Cas9 gene editing, we then created designer gain-of-function mutants in 4 C. elegans K2P channels (and many more since…), which phenocopy those found by Sydney Brenner and Bob Horvitz. This works consistely despite very divergent primary amino acid sequences.

Altoghether, this has been a crucial finding for us because, we were looking for a way to increase the activity of K2P channels in worms to find the genes that are required for their function in vivo.

(On a personnal note, this has solved the entire AIM 3 of our @ERC_Research project *Kelegans*, and then some! Incredibly satisfying when science works out in this way)

And it has opened the way to a (frustratingly) large universe of new projects. Using genetic screens, we have now drawn lines between K2P channels and major cellular players such as Ankyrin, Notch, and most recently, the Dystrophin complex! More about that in the coming year.

Let us know if you have comments, questions, are interested in reagents or collaborations, or just want to chat about our work.

This work was made possible by support from ERC_Research #Kelegans Telethon France #AllianceMyoNeurALP Agence National de la Recherche PIA #LabexICST Université Lyon 1 CNRS and INSERM



All moving boxes are gone. Science going on.

That new lab smell...


After a rocky move across town featuring: snow, ice, rain, city-wide power outage, failing elevators, missing keys, we are (almost) all setup and operational in our brand spanking new lab space.
14 teams and 200 people finally under/on one roof/floor! Now, let's do some science.

Fresh lab space
Fresh lab space

Mind blown...


What a shock when you turn on the microscope and see such a striking subcellular localisation at the tip of every muscle cell. Figuring out how this is possible is going to be an amazing journey.

Mind blown

Reliable CRISPR/Cas9 genome engineering in Caenorhabditis elegans using a single efficient sgRNA and an easily recognizable phenotype

Update 2018-12-14

 144 Labs and counting!  wrmScarlet is freely available for all labs who want it. Visit the following page for the page dedicated to this paper.

To efficiently and freely distribute the wrmScarlet sequence to the community, we have decided to list here all the labs that we have sent the sequence to. Please contact us or anyone on the list to get your copy of the plasmid.
More information here

(6) (1) (1) (6) (4) (5) (2) (1) (1) (1) (9) (77) (9) (1) (4) (3) (2) (1) (7) (2) (1)
21th International Worm Meeting

Great Meeting!

Posters, check! Talk, check! 30 wrmScarlet vectors gone in 3 min, check! 70+ requests to be sent out in the coming days, pending...

And to top it off, Sonia wins the Dr. Matthew J. Buechner Tie Award for service to the community!

July 6, 2017

"Genes to Genomes" announces #Worm17 GSA Poster Award Winners



Institut NeuroMyoGène

We are now part of the Institut NeuroMyoGène.

The INMG is a novel institute dedicated to the study of the nervous and muscular systems. It was created in 2016 in Lyon at the heart of a dense hospital network and of one of the biggest medical universities in France.


2017-03-02 - Finally!

Our paper has just been accepted at G3: GENES, GENOMES, GENETICS!
27 days from submission to acceptance!

Congratulations to the whole team! It was a great collective effort.

 We want to understand how cellular physiology is controled by basic molecular and cellular pathways regulating the biology of potassium-selective ion channels.

Two-pore domain potassium channels (K2P) play a central role in the control of cellular excitability and the regulation of the cell's electrical membrane potential. K2Ps have been widely conserved throughout evolution. They are polymodal ion channels that are subjected to extensive regulation by a diverse set of physical (pH, temperature, mechanical force) and biological signals (lipids, G-protein coupled receptor pathways). They are broadly expressed in excitable and non-excitable cells, and have in turn been implicated in a large spectrum of physiopathological processes, ranging from the regulation of neuronal excitability, respiratory and cardiac function to the control of cell volume, hormone secretion and cell proliferation. Recently, loss- and gain-of-function mutations in K2P channels have been directly linked to human pathologies (Birk Barel syndrome, familial migraine with aura, cardiac conduction disorder).

In contrast to many other ion channel families, comparatively little is known about the molecular and cellular processes that regulate different aspects of the cell biology of K2P channels. For instance we know only of very few factors that specifically regulate the expression, the activity and the localisation of K2P channels at the cell surface. Therefore the central question addressed by our team is: How is the number of active potassium leak channels present at the cell surface controlled in vivo?

To identify novel genes and conserved cellular processes that regulate the biology of K2P channels in vivo we take advantage of the powerful genetic tools available in the model nematode Caenorhabditis elegans. We use the full array of techniques available in C. elegans including genetics, live imaging, electrophysiology and state-of-the-art CRISPR/Cas9 genome engineering and next-generation DNA sequencing. These studies will provide new leads to understand the cellular pathways that control K2P function in other organisms.


CNRS Bronze Medal

Thomas has received his Bronze medal during the official CNRS ceremony on December 4th, 2014

"La Médaille de bronze récompense le premier travail d'un chercheur, qui fait de lui un spécialiste de talent dans son domaine. Cette récompense représente un encouragement du CNRS à poursuivre des recherches bien engagées et déjà fécondes."

Press releases: CNRSUniversité de LyonFaculté des SciencesERC



We are always looking for highly motivated Post-docs, Masters and PhD students to participate in our ERC Starting Grant-funded projects.
Please consult this page before applying.


Our Projects

We endeavor to understand how basic molecular and cellular pathways regulating the biology of potassium-selective ion channels control cellular physiology.

Lab Members

Funding & Support

Our research has been or is funded by the European Research Council (ERC Stg 2013), Fondation Fyssen, AFM Téléthon, and Fondation Maladies Rares.

Our Publications

A generally up-to-date list of our publications and meeting abstracts.

The Newsstand

An ever growing list of papers that stand out.


References to tools that might be of interest.

General & Travel Information


On this page you will find practical information about the lab (location, directions, etc.)

About Lyon

Welcome to Lyon. The capital of the Gauls (Lugdunum) is famous for its gastronomy and architecture.

Organisations & Funding

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Current funding

ERC_logov2        Fondation Fyssen
AFM Téléthon

Past funding

Fondation Fyssen
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