2021-08-09 – Now published in Molecular Genetics and Metabolism!

Great collaboration with the Undiagnosed Diseases Network's Tim Schedl and Stephen Pak.

Papers never tell the “story” behind the science. So much had to happen for this to come together! From eagle-eyed curiosity-driven observations, great timing, to outstanding scientific collaboration. I feel lucky for the opportunity to bring such a meaningful work to fruition.

Kudos to all involved in Europe and the US. Past and present lab members who all contributed their essential piece.

Neurobeachin (NBEA) was initially identified as a candidate gene for autism. Recently, variants in NBEA have been associated with neurodevelopmental delay and childhood epilepsy. Here, we report on a novel NBEA missense variant (c.5899G > A, p.Gly1967Arg) in the Domain of Unknown Function 1088 (DUF1088) identified in a child enrolled in the Undiagnosed Diseases Network (UDN), who presented with neurodevelopmental delay and seizures. Modeling of this variant in the Caenorhabditis elegans NBEA ortholog, sel-2, indicated that the variant was damaging to in vivo function as evidenced by altered cell fate determination and trafficking of potassium channels in neurons. The variant effect was indistinguishable from that of the reference null mutation suggesting that the variant is a strong hypomorph or a complete loss-of-function. Our experimental data provide strong support for the molecular diagnosis and pathogenicity of the NBEA p.Gly1967Arg variant and the importance of the DUF1088 for NBEA function.

Keywords: C. elegans; Epilepsy; Neurobeachin; Neurodevelopmental delay; SEL-2; NEDEGE OMIM 619157; Two-pore domain potassium channels.

New team photo

June 2021

Welcome Uma and Marine.

2021 June

2021-02-05 – Now published in Science Advances!

Great collaboration with Christian Braendle : from wild worms to a single point mutation in an SK potassium channel.

Press release from CNRS

Genetic assimilation—the evolutionary process by which an environmentally induced phenotype is made constitutive—represents a fundamental concept in evolutionary biology. Thought to reflect adaptive phenotypic plasticity, matricidal hatching in nematodes is triggered by maternal nutrient deprivation to allow for protection or resource provisioning of offspring. Here, we report natural Caenorhabditis elegans populations harboring genetic variants expressing a derived state of near-constitutive matricidal hatching. These variants exhibit a single amino acid change (V530L) in KCNL-1, a small-conductance calcium-activated potassium channel subunit. This gain-of-function mutation causes matricidal hatching by strongly reducing the sensitivity to environmental stimuli triggering egg-laying. We show that reestablishing the canonical KCNL-1 protein in matricidal isolates is sufficient to restore canonical egg-laying. While highly deleterious in constant food environments, KCNL-1 V530L is maintained under fluctuating resource availability. A single point mutation can therefore underlie the genetic assimilation—by either genetic drift or selection—of an ancestrally plastic trait.

Funded by ANR

We are hiring!

Molecular, cellular, and clinical investigation of the autism, epilepsy, and neurodevelopmental disorder gene Neurobeachin/NBEA


Neurobeachin is a brain-specific protein required for vesicular trafficking, synaptic structure, and synaptic targeting of neurotransmitter receptors. Neurobeachin mutations have very recently been identified as a genetic cause of autism, neurodevelopmental delay and early generalized epilepsy (Mulhern et al., 2018). During a genetic screen in C. elegans, we have discovered that Neurobeachin can also regulate potassium channel trafficking. Interestingly, these channels play a central role in controlling neuronal excitability. In this project, we propose to combine clinical and fundamental research approaches to better understand the pathophysiology of this new neurological disease, identify cellular processes regulated by Neurobeachin, and find new molecular partners that could serve as potential therapeutic targets in the future.

This project will be a collaborative venture between our team, Tristan T. Sands and Natalie Lippa (Columbia University, New York), Sarah Weckhuysen (VIB & University of Antwerp), Qiang Liu (Bargmann Lab, Rockefeller University, New York), and Maëlle Jospin (Bessereau Lab, Institut NeuroMyoGène, Lyon).

If you are interested in joining the project as a Post-doctoral fellow, Masters, or PhD Student, don't hesitate to contact us!

Newest Preprint out on BioRXiv!


“A single nucleotide change underlies the genetic assimilation of a plastic trait”

Great collaboration with Christian Braendle : from wild worms to a single point mutation in an SK potassium channel. Great how science pulls us all together!


Genetic assimilation - the evolutionary process by which an ancestral environmentally sensitive phenotype is made constitutive - is a fundamental concept in biology. Its evolutionary relevance is debated, and our understanding of its prevalence, and underlying genetics and molecular mechanisms, is poor. Matricidal hatching is an extreme form of maternal provisioning induced by adverse conditions, which varies among Caenorhabditis elegans populations. We identified wild isolates, sampled from natural populations across multiple years and locations, that express a derived state of near-constitutive matricidal hatching. A single amino acid change in kcnl-1, encoding a small-conductance calcium-activated potassium channel subunit, explains most of this variation. A gain-of-function mutation altering the S6 transmembrane domain causes inappropriate activation of the K+ channel, leading to reduced vulval muscle excitability, and thus reduced expulsion of embryos, irrespective of environment. Using reciprocal allelic replacements, we show that this amino acid change is sufficient to induce constitutive matricidal hatching whilst re-establishing the ancestral protein abolishes matricidal hatching and restores egg-laying, thereby doubling lifetime reproductive fitness under benign conditions. While highly deleterious in the laboratory, experimental evolution showed that KNCL-1(V530L) is maintained under fluctuating resource availability. Selection on a single point mutation can therefore underlie the genetic assimilation of an ancestrally plastic trait with drastic life-history consequences.



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

New team photo

February 2020

Big thanks to our pre-COVID-19 interns Ingrid and Fiona. Lots of energy and exciting results.

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).

 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.

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 2020-12-07

 146 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) (6) (2) (1) (1) (1) (9) (78) (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.


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


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

Our Publications

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

Funding & Support

Our research has been or is funded by the European Research Council (ERC Stg 2013), Fondation Fyssen, AFM Téléthon, Fondation Maladies Rares, Agence Nationale de la Recherche (ANR), SOLVE-RD, and Labex CORTEX.

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

Agence Nationale de la Recherche       Fondation Fyssen
AFM Téléthon

Past funding

ERC_logov2       Fondation Fyssen
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