Our goal is to harness the power of proteomics to characterize the molecular defects that cause disease and develop biomarkers that can track the onset and the evolution of disease conditions, the response to treatment, and ultimately serve for the development of new diagnostics and therapeutics.
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.
TOWARDS SINGLE-CELL PROTEOMICS
DEVELOPING SINGLE-CELL TECHNOLOGIES TO CRACK THE FULL COMPLEXITY OF THE HUMAN PROTEOME IN HEALTH, DISEASE, AND RESPONSE TO TREATMENT
Cells are the smallest structural and functional unit of living organisms. For more than a century, scientists have classified cells according to their structure, function, location, and, more recently, their molecular profile, but the characterization of cell types and states has remained limited. We do not comprehensively know our cells: how they are defined by their molecular products, how they vary across tissues, systems, and organs, and how they influence health and disease. This has hampered our ability to study key fundamental domains in biology, and to translate our knowledge to accelerate diagnosis and treatment.
However, transformative advances in experimental and computational methods now provide a unique opportunity to change this situation. Our ability to characterize the protein content of one cell at a time in tissues and organs, coupled with other omics and imaging technologies, is revolutionizing our knowledge. Our group is developing an innovative platform to perform high-throughput surveys of proteins, posttranslational modifications and interactions with single cell resolution.
DEVELOPING NEW GENERATION BIOMARKERS FOR THE MEDICINE OF TOMORROW
We also focus on the quantitative analysis of:
Protein levels using methods that either target specific proteins or achieve large-scale unbiased proteome screens
Protein-protein interactions and their inhibition by small molecules or peptides
The specific methods in place in our lab involve complex workflows mastered by our lab members, including
Protein Affinity Purification coupled to Mass Spectrometry (AP-MS)
Proximity-Dependent Protein Identification (BioID)
Tandem Mass Tag (TMT)-Based Discovery Proteomics
Protein Affinity Capture coupled to quantitative Mass Spectrometry (PAC-qMS)
Phage Display Peptide/Protein Library Screening (PhD)
We invite requests of collaboration not only from IRCM colleagues but also from researchers of other institutions. We usually accept to participate in projects we judge feasible and impactful, when a budget has been already secured by the collaborator. In some cases, we help with the preparation of grant applications. Our current collaborations target multiple diseases/biomarkers, including, but not limited to:
Leukodystrophies / RNA polymerase III
Amyotrophic Lateral Sclerosis / SOD1
Alzheimer's disease / Neuroligins
Cardiometabolic conditions / PCSK9, insulin
COVID-19 / SARS-CoV-2 S glycoprotein and replicase complex
Understanding the molecular defects that cause rare diseases is important to us. Mapping protein-protein interaction changes caused by rare disease-causing mutations is used to build the "Rare Disease Cell Map". This data is made available, often ahead of publication, at OpenforRare.com.
MOST RECENT PAPER
J Proteome Res. 2020 Jan 3;19(1):18-27.
The prefoldin-like module of the PAQosome. Schematic representation of prefoldin and prefoldin-like complexes subunit arrangement.
(A) Subunit arrangement of the canonical prefoldin complex. Archaeal prefoldin is used as a structural reference.
(B) Subunit composition of the canonical prefoldin complex (PFD) and prefoldin-like module (PFDL) of the PAQosome.
(C) Proposed subunit arrangement of the PFDL module.
(D) Simplified phylogenetic tree of the β-prefoldin family with local bootstrap indicated next to the nodes.
10 MOST CITED PAPERS FROM OUR LAB
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.
Mol Cell. 2007 Jul 20;27(2):262-74. (404 citations)
Discovery of the 7SK methylphosphate capping enzyme and a series of chaperone-like proteins that associate with RNA polymerase to regulate its biogenesis, some being components of a chaperone complex later named “Particle for Arrangement of Quaternary structure” (PAQosome)
Coulombe B, Burton ZF.
Microbiol Mol Biol Rev. 1999 Jun;63(2):457-78. (153 citations)
Cloutier P, Lavallée-Adam M, Faubert D, Blanchette M, Coulombe B.
PLoS Genet. 2013;9(1):e1003210. (131 citations)
Robert F, Douziech M, Forget D, Egly JM, Greenblatt J, Burton ZF, Coulombe B.
Mol Cell. 1998 Sep;2(3):341-51. (126 citations)
Douziech M, Coin F, Chipoulet JM, Arai Y, Ohkuma Y, Egly JM, Coulombe B.
Mol Cell Biol. 2000 Nov;20(21):8168-77. (89 citations)
Cloutier P, Al-Khoury R, Lavallée-Adam M, Faubert D, Jiang H, Poitras C, Bouchard A, Forget D, Blanchette M, Coulombe B.
Methods. 2009 Aug;48(4):381-6. (84 citations)
Composition of the R2TP/PFDL co-chaperone complex, later renamed “Particle for Arrangement of Quaternary structure” (PAQosome)
7. Structural Perspective on Mutations Affecting the Function of Multisubunit RNA Polymerases.
Trinh V, Langelier MF, Archambault J, Coulombe B.
Microbiol Mol Biol Rev. 2006 Mar;70(1):12-36. (79 citations)
8. The Protein Interaction Network of the Human Transcription Machinery Reveals a Role for the Conserved GTPase RPAP4/GPN1 and Microtubule Assembly in Nuclear Import and Biogenesis of RNA Polymerase II.
Forget D, Lacombe AA, Cloutier P, Al-Khoury R, Bouchard A, Lavallée-Adam M, Faubert D, Jeronimo C, Blanchette M, Coulombe B.
Mol Cell Proteomics. 2010 Dec;9(12):2827-39. (77 citations)
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.
Nat Commun. 2015 Jul 7;6:7623. *Co-senior authors (75 citations)
Forget D, Langelier MF, Thérien C, Trinh V, Coulombe B.
Mol Cell Biol. 2004 Feb;24(3):1122-31. (73 citations)
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