Stephen Michnick
Gene function and interactions at a genome-wide scale
- Professeur titulaire
-
Faculté de médecine - Département de biochimie et médecine moléculaire
Roger-Gaudry, room E523
Media
Profile
Research expertise
How do cells work? We can pose this question in two ways first, we could ask: what is the function of a gene and second, how do genes function as ensembles. In my lab, we want to be able to test hypotheses both about how genes function and how to study their interactions at a genome-wide scale. The sequencing of some 28,000 human genes has occupied a number of labs around the world and has motivated feverish activity among biomedical researchers to understand functions of genes. However, in the absence of simple methods to establish function, these activities have not advanced significantly. We have a situation analogous to having a complete list of telephone numbers for a city, but few easy ways of linking those numbers to their owners, let alone the relationships among them.
On way to define the function of a newly identified gene is to study the interactions of its product (a proteins) with proteins for which we already know their function. We have developed experimental and theoretical methods that allow us to study how proteins form complexes with each other. Our methods allow us to determine how, when and where in the cell novel proteins interact with known proteins and what are resulting phenotypes specifically associated with a new gene. We also study how groups of proteins work as ensembles to regulate decision making by the cell. We have posed the hypothesis that cells use a limited number of molecular strategies to respond to environmental signals to make decisions to divide, to differentiate into new forms or to die. We are searching for these common mechanisms, which we call « logic motifs » at a genome-wide level. We have already discovered several logic motifs that are necessary to cell survival and for which their interruptions are implicated in several diseases including cancers and diseases of development and aging.
Biography
Professeur au Département de biochimie et médecine moléculaire, Stephen Michnick est titulaire de la Chaire de recherche du Canada sur l'architecture et la dynamique des cellules (niveau 1). Il est membre du Centre Robert-Cedergren de l’Université de Montréal, qui a pour mission de catalyser l’avancement de la recherche fondamentale et de la formation dans les domaines de la bio-informatique et des sciences génomiques. L'objectif de M. Michnick et de son équipe est de comprendre l'intelligence et la mémoire cellulaires. Pour ce faire, ils étudient les principes d'organisation moléculaire et leur influence sur la cellule et sur la mémoire transgénérationnelle.
Awards and recognitions
- Membre de la Société royale du Canada - 2018
Affiliations and responsabilities
Research affiliations
Research units
Titulaire
Membre
Teaching and supervision
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Consequences of local and global chromatin mechanics to adaption and genome stability in the budding yeast Saccharomyces cerevisiae
Cycle : Doctoral
Grade : Ph. D.
Phosphoproteomic study on osmotic shock in Saccharomyces cerevisiae over sub-minute and half- hour timescales
Cycle : Master's
Grade : M. Sc.
Une correction à l’échelle et progressive des données Hi-C révèlent des principes fondamentaux de l’organisation tridimensionnelle et fonctionnelle du génome
Cycle : Master's
Grade : M. Sc.
The regulation and induction of clathrin-mediated endocytosis through a protein aqueous-aqueous phase separation mechanism
Cycle : Doctoral
Grade : Ph. D.
Beyond hairballs: depicting complexity of a kinase-phosphatase network in the budding yeast
Cycle : Doctoral
Grade : Ph. D.
The potential role of the multivalent ionic compound PolyP in the assembly of the liquid nature in the cell
Cycle : Master's
Grade : M. Sc.
Searching for novel gene functions in yeast : identification of thousands of novel molecular interactions by protein-fragment complementation assay followed by automated gene function prediction and high-throughput lipidomics
Cycle : Doctoral
Grade : Ph. D.
Étude de l’effet de la metformine sur la survie cellulaire et sur la réparation de l’ADN chez la levure
Cycle : Master's
Grade : M. Sc.
A proteome-wide strategy reveals a novel mechanism of control of cell cycle progression through modulation of cyclin mRNA stability
Cycle : Doctoral
Grade : Ph. D.
Dissecting cell cycle protein complexes using the pptimized yeast cytosine deaminase protein-fragment complementation assay “You too can play with an edge”
Cycle : Doctoral
Grade : Ph. D.
Clustering algorithms and shape factor methods to discriminate among small GTPase phenotypes using DIC image analysis.
Cycle : Master's
Grade : M. Sc.
Molecular mechanisms for a switch-like mating decision in Saccharomyces cerevisiae
Cycle : Doctoral
Grade : Ph. D.
Détection, caractérisation et visualisation des structures transitoires de protéines par sondage au tryptophane
Cycle : Doctoral
Grade : Ph. D.
Cartographe dynamique des voies de signalisation MAPK chez la levure Saccharomyces cerevisiae
Cycle : Master's
Grade : M. Sc.
Application des librairies de codons dégénérés à l'étude du mécanisme de repliement et de la stabilisation de la structure du domaine liant ras de Raf
Cycle : Doctoral
Grade : Ph. D.
Développement d'un essai de complémentation protéique avec la Renilla luciférase et étude de la voie de biosynthèse des acides aminés aromatiques chez Saccharomyces cerevisiae
Cycle : Master's
Grade : M. Sc.
Development of a binary positive and negative protein fragment complementation assay using yeast cytosine deaminase
Cycle : Master's
Grade : M. Sc.
Étude du mécanisme de repliement de l'ubiquitine de levure par l'introduction de contraintes conformationnelles dans son état dénaturé
Cycle : Master's
Grade : M. Sc.
Les séquences Pierre de Rosette et les interactions protéine-protéine à l'échelle d'un organisme : confrontation avec une approche expérimentale fondée sur la complémentation de fragments protéiques (PCA)
Cycle : Master's
Grade : M. Sc.
Le mécanisme de repliement du Domaine Liant Ras de Raf : implication de la relation "topologie native/mécanisme de repliement" des protéines chez la superfamille de l'ubiquitine
Cycle : Master's
Grade : M. Sc.
Étude de la structure des ARNm et des protéines impliqués dans les maladies neurodégénératives à prion
Cycle : Master's
Grade : M. Sc.
Développement d'un nouvel essai de complémentation protéique pour l'étude des interactions protéine-protéine : le PCA de la bêta-lactamase
Cycle : Master's
Grade : M. Sc.
Visualisation des voies de signalisation intracellulaires dans les cellules vivantes
Cycle : Doctoral
Grade : Ph. D.
Making conformation-specific RNA-binding zinc fingers
Cycle : Doctoral
Grade : Ph. D.
Role of tertiary interactions in determining RNA architecture
Cycle : Doctoral
Grade : Ph. D.
Projects
Research projects
Ultrapotent and broadly neutralizing engineered biologics as therapeutics for SARS-CoV-2
Dynamic protein interaction networks to map molecular origins of envronmental and genomic variations.
Canada Research Chair in Cellular Architecture and Dynamics
DISCOVERY, DEVELOPMENT AND VALISATION OF BIOMARKERS AND THERAGNOSTIC APPROACHES
Structure, dynamics and function of non-membranous organelles
An Integrated Quantitative Biology Initiative (IQBI)
Optimization of specific Frizzled Receptor-targeted antibodies signalling responses - Year two
Drop-based microfluidics (DBM) for single cell studies and ultrahighthroughput phenotypic screens and lab evolution
Persistance des bactéries contre les antibiotiques et la vitrosité de leur cytoplasme
STRUCTURE, DYNAMICS AND CAUSALITY IN PROTEIN INTERACTION NETWORKS
Optimization of specific Frizzled Receptor-targeted antibodies signalling responses
Développement de thérapies contre et tests homogènes rapides pour le SRAS CoV-2 basés sur des anticorps recombinants
Macromolecular interaction analysis using a surface plasmon resonance biosensor
Elucidating the molecular logic of membrane-free compartment function and assembly.
STRUCTURE DYNAMICS AND CONTINGENCY IN SIGNALING REGULATORY NETWORKS
CHAIRE DE RECHERCHE DU CANADA - ARCHITECTURE ET LA DYNAMIQUE DES CELLULES - CELLULAR ARCHITECTURE AND DYNAMICS
An Integrated Quantitative Biology Initiative (IQBI)
Thermodynamique intra-cellulaire: approche intégrée théorie-expérience
Microscopie de confinement à l'échelle nanométrique pour l?observation de la dynamiques et des interactions de l'ADN et des protéines
Thermodynamique intra-cellulaire: approche intégrée théorie-expérience
MEMORY AND CHANCE DURING NUTRIENT SENSING IN BUDDING YEAST
NSERC CREATE TRAINING PROGRAM IN BIONANOMACHINES
STRUCTURE, DYNAMICS AND CONTINGENCY IN NUCLEAR REGULATORY NETWORKS
STRUCTURE, DYNAMICS AND CONTINGENCY IN NUCLEAR REGULATORY NETWORKS
Training program in cellular dynamics of macromolecular complexes
PROBING STRUCTURE AND CAUSALITY IN BIOCHEMICAL NETWORKS WITH DYNAMIC HOMOMERIC PROTEIN COMPLEXES
CIHR EMERGING TEAM IN INTEGRATIVE BIOLOGY OF INFLAMMATORY DISEASES : IL23R AS A CONFIRMED IMMUNE DISEASE PATHWAY : A MODAL FOR TRANSLATING GENETIC DISCOVERIES INTO BETTER DIAGNOSIS AND TREATMENT OF COMMON DISEASES
CIHR EMERGING TEAM IN INTEGRATIVE BIOLOGY OF INFLAMMATORY DISEASES : IL23R AS A CONFIRMED IMMUNE DISEASE PATHWAY: A MODAL FOR TRANSLATING GENETIC DISCOVERIES INTO BETTER DIAGNOSIS AND TREATMENT OF COMMON DISEASES
CIHR EMERGING TEAM IN INTEGRATIVE BIOLOGY OF INFLAMMATION DISEASE : IL23R AS A CONFIRMED IMMUNE DISEASE PATHWAY : A MODEL FOR TRANSLATING GENETIC DISCOVERIES INTO BETTER DIAGNOSIS AND TREATMENT OF COMMON DISEASES
STRUCTURE, DYNAMICS AND CONTINGENCY IN SIGNALING REGULATORY NETWORKS
LOW-VOLUME ITC FOR INVESTIGATING BIOMOLECULAR INTERACTIONS
PROBING STRUCTURE AND CAUSALITY IN BIOCHEMICAL NETWORKS WITH DYNAMIC HOMOMERIC PROTEIN COMPLEXES
STRUCTURE, DYNAMICS AND CONTINGENCY IN SIGNALING REGULATORY NETWORKS
CREATE TRAINING PROGRAM IN BIONANOMACHINES
Outreach
Publications and presentations
Publications
- Tarassov, K. Messier, V., Landry, C.R., Radinovic, S., Serna Molina, M. M., Shames, I., Malitskaya, Y., Vogel, J., Bussey, H. and S. W. Michnick (2008) An in vivo Map of the Yeast Protein Interactome Science Epub May 8.
- Stefan, E., Aquin, S., Berger, N., Landry, C., Bouvier, M., Michnick, S. W., (2007) Quantification of dynamic protein complexes using Renilla luciferase-fragment complementation applied to PKA activities in vivo. Proc Natl Acad Sci U S A, 104, 16,916-16,921.
- Michnick, S. W., Ear, P. H., Manderson, E. N., Remy, I., Stefan, E., (2007) Universal strategies in research and drug discovery based on protein-fragment complementation assays. Nature Rev Drug Discov 6, 569-582.
- MacDonald, M. L., Lamerdin, J., Owens, S., Keon, B. H., Bilter, G. K., Shang, Z., Huang, Z., Yu, H., Dias, J., Minami, T., Michnick, S. W.*, Westwick, J. K., (2006) Identifying off-target effects and hidden phenotypes of drugs in human cells. Nature Chem Biol 2, 329-337.
- Remy, I., Montmarquette, A., Michnick, S. W., (2004) PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nature Cell Biol 6, 358-65.
Disciplines
- Biochemistry
- Bioinformatics
- Genomics
- Molecular Biology
- Molecular Medicine
Areas of expertise
- Genomics
- Genes
- Proteomics
- Nucleic Acids
- Bioinformatics
- Cell
- Chromosome (Living Organisms)
- Enzymes and Proteins
- Gene (Living Organisms)
- Biological and Biochemical Mechanisms
- Bioactive Molecules
- Macromolecules
- Cell Signaling and Cancer
- COVID-19
- COVID19