Translational Proteomics lab

Director, Benoit Coulombe PhD

Professor of Biochemistry and Molecular Medicine, Université de Montréal

Person in Charge of Responsible Conduct in Research (PCRCR), IRCM

Associate Editor, Molecular Brain

Editorial Board Member, Biomolecules

Biography

Exploring the Universe of Protein-Protein Interactions

Mission

Mission

Discovery of the PAQosome

Our Technology Platforms

Affinity Purification coupled with Mass Spectrometry (AP-MS)
Purification and characterization of soluble protein complexes

Proximity-dependent labeling coupled with Mass spectrometry (BioID-MS)
Characterization of insoluble protein complexes

Mass Spectrometry Immuno Affinity (MSIA)
Targeted protein quantification

FAB-Phage Display screening (PhD)
Unbiased discovery of FAB-phages recognizing specific cell epitopes

Quantitative Single-Cell Proteomics (SCP)
Identification of proteins at single-cell resolution

Small-molecule screening (SMS)
Discovery of small molecules affecting biological/biochemical functions

Artificial Intelligence-Alphafold2 multimer-Binary (AI-AF2m-Binary)
Determination of pairwise protein-protein interactions in the AlphaFold database

MOST RECENT ARTICLE

Discovery of a drug that stimulates protein complex assembly

Pinard M, Dastpeyman S, Poitras C, Bernard G, Gauthier MS, Coulombe B.

Riluzole partially restores RNA polymerase III complex assembly in cells expressing the leukodystrophy-causative variant POLR3B R103H

Mol Brain. 2022 Nov 30;15(1):98. doi: 10.1186/s13041-022-00974-z.

Schematic representation of Pol III assembly defects caused by various mutated subunits

FEATURED ARTICLES

Discovery of a novel mode of substrate selection by the PAQosome

Pinard M, Cloutier P, Poitras C, Gauthier MS, Coulombe B.

Unphosphorylated Form of the PAQosome Core Subunit RPAP3 Binds Ribosomal Preassembly Complexes to Modulate Ribosome Biogenesis

J Proteome Res. 2022 Apr 1;21(4):1073-1082. doi: 10.1021/acs.jproteome.1c00938

PAQosome Subunit RPAP3 Binds Ribosomal Preassembly Complexes

Discovery of a novel neurodegenerative disorder and causative mutations

Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G.

De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy

Am J Hum Genet. 2021 Jan 7;108(1):186-193. doi: 10.1016/j.ajhg.2020.12.002

Model of POLR3 in transcription initiation state

A mechanistic model for interactome biogenesis

Coulombe B, Cloutier P, Gauthier MS.

How do our cells build their protein interactome?

Nat Commun. 2018 Jul 27;9(1):2955. doi: 10.1038/s41467-018-05448-2.

Representation of putative alternative PAQosomes

Summary of the PAQosome structure and function

Houry WA, Bertrand E, Coulombe B.

The PAQosome, an R2TP-Based Chaperone for Quaternary Structure Formation

Trends Biochem Sci. 2018 Jan;43(1):4-9. doi: 10.1016/j.tibs.2017.11.001.

Schematic of the PAQosome Structure, Adaptors, and Clients

Discovery of leukodystrophy-causing mutations that target assembly of RNA pol III

Thiffault I, Wolf NI, Forget D, Guerrero K, Tran LT, Choquet K, Lavallée-Adam M, Poitras C, Brais B, Yoon G, Sztriha L, Webster RI, Timmann D, van de Warrenburg BP, Seeger J, Zimmermann A, Máté A, Goizet C, Fung E, van der Knaap MS, Fribourg S, Vanderver A, Simons C, Taft RJ, Yates JR 3rd, Coulombe B, Bernard G.

Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III

Nat Commun. 2015 Jul 7;6:7623. doi: 10.1038/ncomms8623.

Impact of POLR1C mutations on polymerase assembly and nuclear import

Discovery of molecular adaptors for substrate selection by the PAQosome

Cloutier P, Poitras C, Durand M, Hekmat O, Fiola-Masson É, Bouchard A, Faubert D, Chabot B, Coulombe B.

R2TP/Prefoldin-like component RUVBL1/RUVBL2 directly interacts with ZNHIT2 to regulate assembly of U5 small nuclear ribonucleoprotein

Nat Commun. 2017 May 31;8:15615. doi: 10.1038/ncomms15615.

R2TP substrates

Selected publications

Using machine learning to build protein interaction networks

Jeronimo C, Forget D, Bouchard A, Li Q, Chua G, Poitras C, Thérien C, Bergeron D, Bourassa S, Greenblatt J, Chabot B, Poirier GG, Hughes TR, Blanchette M, Price DH, Coulombe B.

Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme

Mol Cell. 2007 Jul 20;27(2):262-274. doi: 10.1016/j.molcel.2007.06.027.

Application of machine learning to construct an interaction network for the human RNA polymerase II transcription machinery, leading to discovery of the 7SK capping enzyme