Thomas

Short Bio

Thomas Boulin heads the team "Molecular and cellular neurobiology of C. elegans" at the Institut NeuroMyoGène - CNRS/INSERM/Université Lyon 1. He has worked on various aspects of C. elegans neurobiology for the past 20 years.

During his PhD with Oliver Hobert at Columbia University, he studied molecular and cellular mechanisms controling the formation and the maintenance of the C. elegans nervous system (Buelow, Neuron 2003). As a post-doc with Jean-Louis Bessereau at École Normale Supérieure in Paris, he developed genetic and electrophysiological strategies to study synaptic function and acetylcholine receptor modulation (Boulin, PNAS 2008 ; Boulin, Nature Neuroscience 2012).

His team is now focusing on the role played by potassium channels in the control of cellular excitability and the regulation of the cell's membrane potential. The goal of the team is to investigate the biology of these widely-conserved ion channels in their native cellular context by taking advantage of the powerful genetic tools available in C. elegans.

Academic Positions & Education

  • Since 2013   Group leader at Institut NeuroMyoGène - INMG.
  • Since 2009   Tenured researcher at CNRS, CRCN.
  • 2016        Habilitation à diriger des Recherches (HDR), Université Lyon 1.

  • 2020 - 2025 Member of LabEx CORTEX
  • Since 2019   Scientific Council; Association Aïda, associationaida.org.
  • Since 2016   Scientific Advisor, CNRS UMS 3421.
  • 2013 - 2019 Member of the Management Committee of COST Action BM1408.

  • 2005 - 2009 Post-doctoral fellow with Jean-Louis Bessereau, École Normale Supérieure, Paris.
  • 2001 - 2005 PhD with Oliver Hobert, Columbia University, HHMI, New York.
  • 2000 - 2001 Masters / D.E.A. Biologie Moléculaire et Cellulaire du Dévelopement (BMCD), Université Paris 6.
  • 1998 - 2002 Student of the École Normale Supérieure (ENS Paris).

Publications

18| Mutation of a single residue promotes gating of vertebrate and invertebrate two-pore domain potassium channels.
Ben Soussia I, El Mouridi S, Kang D, Leclercq-Blondel A, Khoubza L, Tardy P, Zariohi N, Gendrel M, Lesage F, Kim EJ, Bichet D, Andrini O, Boulin T.
Nature Communications (2019) Download PDF here
CRISPR/Cas9 genome engineering strategies allow the directed modification of the Caenorhabditis elegans genome to introduce point mutations, generate knock-out mutants, and insert coding sequences for epitope or fluorescent tags. Three practical aspects, however, complicate such experiments. First, the efficiency and specificity of single-guide RNAs (sgRNA) cannot be reliably predicted. Second, the detection of animals carrying genome edits can be challenging in the absence of clearly visible or selectable phenotypes. Third, the sgRNA target site must be inactivated after editing to avoid further double-strand break events. We describe here a strategy that addresses these complications by transplanting the protospacer of a highly efficient sgRNA into a gene of interest to render it amenable to genome engineering. This sgRNA targeting the dpy-10 gene generates genome edits at comparatively high frequency. We demonstrate that the transplanted protospacer is cleaved at the same time as the dpy-10 gene. Our strategy generates scarless genome edits because it no longer requires the introduction of mutations in endogenous sgRNA target sites. Modified progeny can be easily identified in the F1 generation, which drastically reduces the number of animals to be tested by PCR or phenotypic analysis. Using this strategy, we reliably generated precise deletion mutants, transcriptional reporters, and translational fusions with epitope tags and fluorescent reporter genes. In particular, we report here the first use of the new red fluorescent protein mScarlet in a multicellular organism. wrmScarlet, a C. elegans-optimized version, dramatically surpassed TagRFP-T by showing an eightfold increase in fluorescence in a direct comparison.
17| CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors.
D'Alessandro M, Richard M, Stigloher C, Gache V, Boulin T, Richmond JE, Bessereau JL.
Elife (2018) Download PDF here
16| Reliable CRISPR/Cas9 Genome Engineering in Caenorhabditis elegans Using a Single Efficient sgRNA and an Easily Recognizable Phenotype.
El Mouridi S, Lecroisey C, Tardy P, Mercier M, Leclercq-Blondel A, Zariohi N, Boulin T.
G3 (Bethesda) (2017) Download PDF here
CRISPR/Cas9 genome engineering strategies allow the directed modification of the Caenorhabditis elegans genome to introduce point mutations, generate knock-out mutants, and insert coding sequences for epitope or fluorescent tags. Three practical aspects, however, complicate such experiments. First, the efficiency and specificity of single-guide RNAs (sgRNA) cannot be reliably predicted. Second, the detection of animals carrying genome edits can be challenging in the absence of clearly visible or selectable phenotypes. Third, the sgRNA target site must be inactivated after editing to avoid further double-strand break events. We describe here a strategy that addresses these complications by transplanting the protospacer of a highly efficient sgRNA into a gene of interest to render it amenable to genome engineering. This sgRNA targeting the dpy-10 gene generates genome edits at comparatively high frequency. We demonstrate that the transplanted protospacer is cleaved at the same time as the dpy-10 gene. Our strategy generates scarless genome edits because it no longer requires the introduction of mutations in endogenous sgRNA target sites. Modified progeny can be easily identified in the F1 generation, which drastically reduces the number of animals to be tested by PCR or phenotypic analysis. Using this strategy, we reliably generated precise deletion mutants, transcriptional reporters, and translational fusions with epitope tags and fluorescent reporter genes. In particular, we report here the first use of the new red fluorescent protein mScarlet in a multicellular organism. wrmScarlet, a C. elegans-optimized version, dramatically surpassed TagRFP-T by showing an eightfold increase in fluorescence in a direct comparison.
15| Microtubule severing by the katanin complex is activated by PPFR-1-dependent MEI-1 dephosphorylation.
Gomes JE, Tavernier N, Richaudeau B, Formstecher E, Boulin T, Mains PE, Dumont J, Pintard L.
Journal of Cell Biology (2013) Download PDF here
14| Biosynthesis of ionotropic acetylcholine receptors requires the evolutionarily conserved ER membrane complex.
Richard M, Boulin T, Robert VJ, Richmond JE, Bessereau JL.
PNAS (2013) Download PDF here
13| Positive modulation of a Cys-loop acetylcholine receptor by an auxiliary transmembrane subunit.
Boulin T, Rapti G, Briseño-Roa L, Stigloher C, Richmond JE, Paoletti P, Bessereau JL.
Nature Neuroscience (2012) Download PDF here
Auxiliary subunits regulate the trafficking, localization or gating kinetics of voltage- and ligand-gated ion channels by associating tightly and specifically with pore-forming subunits. However, no auxiliary subunits have been identified for members of the Cys-loop receptor superfamily. Here we identify MOLO-1, a positive regulator of levamisole-sensitive acetylcholine receptors (L-AChRs) at the Caenorhabditis elegans neuromuscular junction. MOLO-1 is a one-pass transmembrane protein that contains a single extracellular globular domain-the TPM domain, found in bacteria, plants and invertebrates, including nonvertebrate chordates. Loss of MOLO-1 impairs locomotion and renders worms resistant to the anthelmintic drug levamisole. In molo-1 mutants, L-AChR-dependent synaptic transmission is reduced by half, while the number and localization of receptors at synapses remain unchanged. In a heterologous expression system, MOLO-1 physically interacts with L-AChRs and directly enhances channel gating without affecting unitary conductance. The identification of MOLO-1 expands the mechanisms for generating functional and pharmacological diversity in the Cys-loop superfamily.
12| From genes to function : the C. elegans genetic toolbox.
Boulin T, Hobert O
Wiley Interdisciplinary Reviews : Developmental Biology (2011) Download PDF here
11| Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance.
Boulin T, Fauvin A, Charvet C, Cortet J, Cabaret J, Bessereau JL, Neveu C.
British Journal of Pharmacology (2011) Download PDF here
10| A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans.
Jospin M, Qi YB, Stawicki TM, Boulin T, Schuske KR, Horvitz HR, Bessereau JL, Jorgensen EM, Jin Y.
PLoS Biology (2009) Download PDF here
9| The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in Caenorhabditis elegans.
Benard C, Tjoe N, Boulin T, Recio J, Hobert O. (2009)
Genetics (2009) Download PDF here
8| Eight genes are required for functional reconstitution of the C. elegans levamisole-sensitive acetylcholine receptor.
Boulin T*, Gielen M*, Richmond J, Williams DC, Paoletti P and Bessereau JL.
PNAS (2008) Download PDF here
7| Mos1-mediated insertional mutagenesis in Caenorhabditis elegans.
Boulin T, Bessereau JL
Nature Protocols , (2007) Download PDF here
6| A novel Eph receptor-interacting IgSF protein provides C. elegans motoneurons with midline guidepost function.
Boulin T, Pocock R, Hobert O.
Current Biology (2006) 16(19):1871-83.
Reviewed by Quinn CC, Wadsworth, WG. Current Biology, 2006 ; 16(22):R954-5.
5| Developmental regulation of whole cell capacitance and membrane current in identified interneurons in C. elegans.
Faumont S, Boulin T, Hobert O, Lockery SR.
J. Neurophysiology (2006) 95(6):3665-73.
4| Reporter gene fusions
Boulin T*, Etchberger JF*, Hobert O.
WormBook (2006) Apr 5 ; 1-23.
3| Characterization of Mos1 Mediated Mutagenesis in C. elegans : A Method for the Rapid Identification of Mutated Genes.
Williams DC, Boulin T, Ruaud AF, Jorgensen EM, Bessereau JL.
Genetics (2005) 169(3):1779-85.
2| Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position.
Bülow H*, Boulin T*, Hobert O.
Neuron (2004) 42(3):367-74.
1| Identification of spatial and temporal cues that regulate postembryonic expression of axon maintenance factors in the C. elegans ventral nerve cord.
Aurelio O, Boulin T, Hobert O.
Development (2003) 130(3):599-610.

Favourite quote
Progress in science depends on new techniques, new discoveries and new ideas, probably in that order.

Sydney Brenner

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