Thomas [dot] Boulin [at] univ-lyon1 [dot] fr
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 15 years, first as a PhD student with Oliver Hobert (Columbia University), and later as a post-doc and CNRS researcher with Jean-Louis Bessereau (ENS Paris, now Université Lyon 1), where he developed genetic strategies and electrophysiological tools to study levamisole-sensitive acetylcholine receptors.
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.
- 2016 - now Group leader at Institut NeuroMyoGène - INMG.
- 2013 - 2016 Group leader at CGphiMC — Université Lyon 1.
- 2013 Researcher at CNRS (CR1).
- 2009 - 2013 Researcher at CNRS (CR2).
- 2005 - 2009 Post-doctoral fellow with Jean-Louis Bessereau, INSERM U789, 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).
Personal Funding & prizes
- 2014 CNRS Bronze Medal
- 2007 - 2009 INSERM Junior Contract — 2007-2009
- 2007 Prix René Descartes, Congrès Jeunes Chercheurs
- 2005 - 2007 EMBO Long term Post-doctoral Fellowship
- 2006 PhD Prize of the French Society of Neurosciences
- 2002 - 2005 Boehringer Ingelheim Fonds PhD Fellowship
El Mouridi S, Lecroisey C, Tardy P, Mercier M, Leclercq-Blondel A, Zariohi N, Boulin T.
G3 (Bethesda) (2017) May 5;7(5):1429-1437.
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) Aug 5;202(3):431-9.
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) Mar ;110(11):E1055-63.
The number of nicotinic acetylcholine receptors (AChRs) present in the plasma membrane of muscle and neuronal cells is limited by the assembly of individual subunits into mature pentameric receptors. This process is usually inefficient, and a large number of the synthesized subunits are degraded by endoplasmic reticulum (ER)-associated degradation. To identify cellular factors required for the synthesis of AChRs, we performed a genetic screen in the nematode Caenorhabditis elegans for mutants with decreased sensitivity to the cholinergic agonist levamisole. We isolated a partial loss-of-function allele of ER membrane protein complex-6 (emc-6), a previously uncharacterized gene in C. elegans. emc-6 encodes an evolutionarily conserved 111-aa protein with two predicted transmembrane domains. EMC-6 is ubiquitously expressed and localizes to the ER. Partial inhibition of EMC-6 caused decreased expression of heteromeric levamisole-sensitive AChRs by destabilizing unassembled subunits in the ER. Inhibition of emc-6 also reduced the expression of homomeric nicotine-sensitive AChRs and GABAA receptors in C. elegans muscle cells. emc-6 is orthologous to the yeast and human EMC6 genes that code for a component of the recently identified ER membrane complex (EMC). Our data suggest this complex is required for protein folding and is connected to ER-associated degradation. We demonstrated that inactivation of additional EMC members in C. elegans also impaired AChR synthesis and induced the unfolded protein response. These results suggest that the EMC is a component of the ER folding machinery. AChRs might provide a valuable proxy to decipher the function of the EMC further.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) Oct ;15(10):1374-81.
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) Nov ;1(1):114-137.
This review aims to provide an overview of the technologies which make the nematode Caenorhabditis elegans an attractive genetic model system. We describe transgenesis techniques and forward and reverse genetic approaches to isolate mutants and clone genes. In addition, we discuss the new possibilities offered by genome engineering strategies and next-generation genome analysis tools.11| A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans.
Boulin T, Fauvin A, Charvet C, Cortet J, Cabaret J, Bessereau JL, Neveu C.
British Journal of Pharmacology (2011) Nov ;164(5):1421-32 ; Epub ahead of print Apr 12
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) Dec ;7(12):e1000265
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) Nov ;183(3):917-27.
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) 105(47):18590-18595.
7| Mos1-mediated insertional mutagenesis in Caenorhabditis elegans.
Boulin T, Bessereau JL
Nature Protocols , (2007) 2(5):1276-86.
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.