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Creating new
knowledge
Exploring new avenues to develop tomorrow’s medical knowledge through an approach that integrates basic and clinical research
Our research units are led by principal investigators who collaborate in a spirit of collegiality and with the vision of bridging the gap between research and patients. They train the next generation of scientists and are independent and creative minds who work tirelessly to improve health.
Current research
“We are developing state-of-the-art methods for high-sensitivity profiling of the human proteome at single-cell resolution. More specifically, we aim to understand the folding and assembly of protein complexes by the HSP90/PAQosome chaperone machinery, and its dysregulation in various diseases.”
Benoit Coulombe, research director
Translational Proteomics
Our lab combines the use of high-performance mass spectrometry, AI and iPSC/organoid cell models to advance biology and understand disease, most particularly leukodystrophy, Alzheimer's, amyotrophic lateral sclerosis (ALS), and respiratory viral infections with high pandemic risk.
Our research lay upstream of the development of a new medical paradigm, called cell-based interceptive medicine, which is spreading rapidly in Europe ("LifeTime Initiative") and aims to treat diseases at the first signs of disruption of gene expression networks in cells that branch off from health to disease. To accelerate the development of cell-based interceptive medicine in Québec and Canada, our team has set up the 37TrillionCells initiative which brings together a number of projects that use common single-cell and omics technologies.
Our work is based on national and international partnerships with academic and industrial groups, promoting an open science approach to accelerate the discovery of medical treatments and the creation of wealth for the economy of Quebec and Canada.
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PAIRS is an algorithm that uses the AI system AlphaFold-Multimer (DeepMind/Google) to identify direct physical protein-protein interactions of human or viral origin. Previously named AlphaFold-pairs, PAIRS has been developed by the Translational Proteomics lab at the Montreal Clinical Research Institute (IRCM).
Most Recent Article
Several drugs target the PAQosome subunits
Pinard M, Moursli A, Coulombe B.
Drugs targeting the particle for arrangement of quaternary structure (PAQosome) and protein complex assembly
Expert Opin Drug Discov. 2023 Oct 15:1-15. doi: 10.1080/17460441.2023.2267974
Featured Articles
Variants of RNA polymerase III subunits strike again and cause leukodystrophy
Macintosh J, Perrier S, Pinard M, Tran LT, Guerrero K, Prasad C, Prasad AN, Pastinen T, Thiffault I, Coulombe B, Bernard G.
Biallelic pathogenic variants in POLR3D alter tRNA transcription and cause a hypomyelinating leukodystrophy: A case report
Front Neurol. 2023 Oct 13. doi: 10.3389/fneur.2023.1254140
AI predicts protein direct physical interactions with AlphaFold-pairs
Poitras C, Lamontage F, Grandvaux N, Song H, Pinard M, Coulombe B.
High-accuracy mapping of human and viral direct physical protein-protein interactions using the novel computational system AlphaFold-pairs
bioRxiv. 2023 Aug 30:2023.08.29.555151. doi: 10.1101/2023.08.29.555151. Preprint.
A mouse model to study RNA polymerase III-related leukodystrophies
Michell-Robinson M, Watt KEN, Grouza V, Macintosh J, Pinard M, Tuznik M, Chen X, Darbelli L, Wu CL, Perrier S, Chitsaz D, Uccelli NA, Liu H, Cox TC, Müller C, Kennedy TE, Coulombe B, Rudko D, Trainor PA, Bernard G.
Hypomyelination, hypodontia and craniofacial abnormalities in a Polr3b mouse model of leukodystrophy
Brain. 2023 Aug 28:awad249. doi: 10.1093/brain/awad249
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.
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
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
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.
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.
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.
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.
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.
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