Our goal is to develop and apply high-specificity, high-sensitivity methods for mapping human protein-protein interactions (the interactome) and for characterizing interactome changes in various genetic and viral diseases. This knowledge accelerates biomarker and drug discovery en route to the development of more efficient diagnostics and therapeutics for various diseases.
Our group adopts a resolutely innovative modus operandi, which contributes to shaking up our classic methods by creating a transdisciplinary and open ecosystem where totally distinct approaches collide to allow both the study of the atomic structure of proteins and their organization in complex networks, both the analysis of microscopic model systems and of patient cohorts, both the screening of small molecules and their development to create affordable drugs.
To join our group as a graduate student or a postdoctoral fellow, please send a motivation letter and a complete CV by email directly to Benoit.Coulombe@ircm.qc.ca. Only candidates of interest will be contacted.
Protein-protein interactions are at the heart of SARS-CoV-2 replication and propagation. The spike glycoprotein interacts with receptors at the surface of host cells to determine viral tropism. The SARS-CoV-2 RNA polymerase associates with other viral proteins to support genome replication and transcription. Our group is studying the function and regulation of protein-protein interactions involved in the SARS-CoV-2 replication cycle.
Mutations causing rare diseases, including leukodystrophies and amyotrophic lateral sclerosis, often perturb interactions of the mutated gene product with cellular partners. Our group is characterizing early protein-protein interaction defects causing rare diseases, and seeking to discover small molecules or peptides to restore these molecular defects.
Protein Affinity Capture coupled to quantitative Mass Spectrometry (PAC-qMS) harnesses the power of antibody-antigen interactions to capture and quantify a protein of interest (antigen) with high specificity and sensitivity. We have developed assays to measure a number of proteins involved in cardiometabolic diseases, including PCSK9 and Insulin, as well as the synaptic adhesion factor neuroligin involved in various types of diseases.
The Particle for Arrangement of Quaternary structure (PAQosome) plays a crucial role in the assembly of many protein complexes, including RNA polymerases, snRNPs, the ribosome and many others. Our group played a central role in human PAQosome discovery and continues to study its function and regulation.
10 MOST SIGNIFICANT DISCOVERIES FROM OUR LAB
Robert F, Douziech M, Forget D, Egly JM, Greenblatt J, Burton ZF, Coulombe B.
Wrapping of promoter DNA around the RNA polymerase II initiation complex induced by TFIIF.
Mol Cell. 1998 Sep;2(3):341-51.
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):262-74.
Cloutier P, Lavallée-Adam M, Faubert D, Blanchette M, Coulombe B.
A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.
PLoS Genet. 2013;9(1):e1003210.
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.
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.
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.
Coulombe B, Cloutier P, Gauthier MS.
How do our cells build their protein interactome?
Nat Commun. 2018 Jul 27;9(1):2955.
Gauthier MS, Awan Z, Bouchard A, Champagne J, Tessier S, Faubert D, Chabot K, Garneau PY, Rabasa-Lhoret R, Seidah NG, Ridker PM, Genest J, Coulombe B.
Posttranslational modification of proprotein convertase subtilisin/kexin type 9 is differentially regulated in response to distinct cardiometabolic treatments as revealed by targeted proteomics.
J Clin Lipidol. 2018 Jul-Aug;12(4):1027-1038.
Mendes MI, Gutierrez Salazar M, Guerrero K, Thiffault I, Salomons GS, Gauquelin L, Tran LT, Forget D, Gauthier MS, Waisfisz Q, Smith DEC, Simons C, van der Knaap MS, Marquardt I, Lemes A, Mierzewska H, Weschke B, Koehler W, Coulombe B, Wolf NI, Bernard G.
Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.
Am J Hum Genet. 2018 Apr 5;102(4):676-684.
Cloutier P, Poitras C, Faubert D, Bouchard A, Blanchette M, Gauthier MS, Coulombe B.
Upstream ORF-Encoded ASDURF Is a Novel Prefoldin-like Subunit of the PAQosome.
J Proteome Res. 2020 Jan 3;19(1):18-27.
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