Daniel Zenklusen
RNA regulation and disease
- Professeur titulaire
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Faculté de médecine - Département de biochimie et médecine moléculaire
Pavillon J.-Armand-Bombardier, local 3033
Portrait
Expertise de recherche
Regulating gene expression, the process of reading and interpreting genetic information is a central task for all living organisms, and errors in this process cause many diseases, including cancer and various neurodegenerative diseases. We seek to understand the processes that modulate regulated expression of genes in cells by investigating the spatio-temporal regulation of RNA metabolism, focusing on studying the biology of the main molecule within this process, RNA. Combining single-molecule and super-resolution microscopy approaches with biochemistry, genomics and genetics we aim to gain a better understanding of the general rules that governing RNA metabolism, establishing the basis for a better understanding of cell physiology and treatment of complex diseases. Among our current research projects, we investigate how the organization and composition of (pre-)mRNP and lncRNP modulate their function, how the structural organization of the nucleus in different phase separated compartment contributes to the regulation of RNA expression, and how the nuclear pore complex regulates the RNA transport to the cytoplasm.
Biographie
Daniel Zenklusen est titulaire d'un doctorat en microbiologie de l'Université de Lausanne et a effectué des études postdoctorales dans le laboratoire de Robert H Singer à l'Albert Einstein College of Medicine à New York. Il est professeur au Département de biochimie et médecine moléculaire de la Faculté de médecine de l'UdeM depuis 2010.
Formation
- 2002 — Doctorat — Biologie cellulaire — Université de Lausanne
- 1998 — Maîtrise — Biologie moléculaire — Universität Bern
Affiliations et responsabilités
Enseignement et encadrement
Recrutement en recherche
Multiple PhD and postdoctoral positions are available in the Zenklusen laboratory. Available projects aim to study fundamental aspects of RNP biology (including the biology in introns and other coding and non-coding RNAs), to decipher mechanisms that facilitate the formation and composition of RNA-protein complexes, their topological organization, and how this facilitates gene expression. Moreover, we want to understand, how defects in RNPs lead to various disease phenotypes, including cancer and various neurodegenerative diseases. Projects will employ multidisciplinary approaches in the areas of single-molecule and super-resolution microscopy, RNA/protein biochemistry, genomics and CRISPR-Cas9-mediated genome editing, using mammalian cell culture models.
Applicants should have expertise/undergraduate degree in cell biology, biochemistry and/or biophysics and experience in working with RNA, RNA-protein interactions and/or single molecule biophysical methods.
Interested applicants should email a CV and letter of introduction, proposed start date, a list of publications (for postdoc candidates), names of two or three references who may be contacted for letters, and a brief description of future research interests to daniel.r.zenklusen@umontreal.ca
Enseignement
Cours siglés (session en cours uniquement)
Programmes
Encadrement
Thèses et mémoires dirigés (dépôt institutionnel Papyrus)
Investigation des fonctions de la protéine du pore nucléaire TPR en utilisant la microscopie à molécule unique
Cycle : Maîtrise
Diplôme obtenu : M. Sc.
Deciphering intron structural organization and metabolism using super-resolution microscopy
Cycle : Maîtrise
Diplôme obtenu : M. Sc.
Characterising (pre-)mrnp organisation at different stages of gene regulation using single-molecule microscopy
Cycle : Doctorat
Diplôme obtenu : Ph. D.
Deciphering mRNP – nuclear pore interactions : study of basket protein dynamics in budding yeast
Cycle : Doctorat
Diplôme obtenu : Ph. D.
Single molecule characterization of the roles of long non-coding RNAs in eukaryotic transcription regulation
Cycle : Doctorat
Diplôme obtenu : Ph. D.
Dissection du processus d’export des ARNm nucléaires par des approches de molécules uniques chez Saccharomyces cerevisae
Cycle : Maîtrise
Diplôme obtenu : M. Sc.
Les patrons d’expression de gènes : ont-ils évolué avec la complexité des organismes?
Cycle : Maîtrise
Diplôme obtenu : M. Sc.
Projets
Projets de recherche
Investigate features and dynamics of intron RNP topology and its role in modulating RNA metabolism
Determine the composition and structural organization of non-translating mRNAs
Determining the role of the nuclear basket protein Mlp1/TPR in mRNA homeostasis
Investigate features and dynamics of intron RNP biology and its role in modulating RNA metabolism
Deciphering the role of nuclear organization in mRNA and lncRNA nuclear retention
Nuclear Transport Meeting 2022
Investigate The Role Of mRNP Structure In Translation And RNA Metabolism
Disséquer les mécanismes régulant l'expression des gènes utilisant des approches de molécules uniques
Determining the pathways, components and functional niches that define specialized ribosomes.
Drop-based microfluidics (DBM) for single cell studies and ultrahighthroughput phenotypic screens and lab evolution
DISSECTING THE ROLE OF THE NUCLEAR BASKET IN REGULATING MRNA METABOLISM
Supplément COVID-19 CRSNG_Deciphering the role of nuclear organization in mRNA and lncRNA nuclear
Disséquer les mécanismes régulant l'expression des gènes utilisant des approches de molécules uniques
DISSECTING THE KINETICS AND MECHANISMS OF GENE EXPRESSION PROCESSES USING SINGLE CELL AND SINGLE MOLECULE RESOLUTION LIVE CELL IMAGING
DISSECTING THE DYNAMICS OF TRANSCRIPTION REGULATION AT A SINGLE CELL LEVEL
DETERMINING THE KINETICS AND MECHANISM OF MRNA EXPORT
Training program in cellular dynamics of macromolecular complexes
ANALYSE DE LA DYNAMIQUE DE L'EXPRESSION DES GENES DANS DES CELLULES UNIQUES
ANALYSE DE LA DYNAMIQUE DE L'EXPRESSION DES GENES DANS DES CELLULES UNIQUES
DISSECTING THE DYNAMICS OF TRANSCRIPTION REGULATION AT A SINGLE CELL LEVEL
ANALYSE DE LA DYNAMIQUE DE L'EXPRESSION DES GÈNES DANS DES CELLULES UNIQUES
DETERMINING THE KINETICS AND MECHANISM OF MRNA EXPORT
Rayonnement
Publications et communications
Publications
Dernières publications
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Bensidoun P, Reiter T, Montpetit B, Zenklusen D#, Oeffinger M#. Nuclear mRNA metabolism drives selective basket assembly on a subset of nuclear pores in budding yeast. Molecular Cell 2022 Oct 20;82(20):3856-3871.e6. #co-corresponding authors
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Zhao C, Biondic S, Vandal K, Björklund ÅK, Hagemann-Jensen M, Sommer TM, Canizo J, Clark S, Raymond P, Zenklusen D, Rivron N, Reik W, Petropoulos S. Single-cell multi-omics of human preimplantation embryos shows susceptibility to glucocorticoids. Genome Research 2022 Aug 10;32(9):1627-41.
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Jayabalan AK, Adivarahan S, Koppula A, Abraham R, Batish M, Zenklusen D, Griffin DE and Leung AKL. Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity. Proc Natl Acad Sci U S A, 2021 118 (6) e2021719118
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Adivarahan S, Livingston N, Nicholson B, Rahman S, Wu B, Rissland O, Zenklusen D. Spatial organization of single mRNPs at different stages of the gene expression pathway. Molecular Cell. 08 Nov 2018, 72(4):727-738.e5
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Lessard F, Igelmann S, Huot G, Le Calvé B, Montero B, St-Germain E, Mignacca L, Deschênes-Simard X, Moiseeva O, Zorca CE, Zenklusen D, Brakier-Gingras L, Bourdeau V and Ferbeyre G. Defective ribosome biogenesis in senescence reveals a novel checkpoint pathway to block cyclin dependent kinases. Nature Cell Biology. Jul;20(7):789-799
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Rahman S, Zorca C, Traboulsi T, Noutahi E, Krause M, Mader S and Zenklusen D. Single-cell profiling reveals that eRNA accumulation at enhancer-promoter loops is not required to sustain transcription. Nucleic Acid Research. 2017 Apr 7;45(6):3017-3030.
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Fernandez-Martinez J, Kim SJ, Shi Y, Upla P, Pellarin R, Gagnon M, Chemmama IE, Wang J, Nudelman I, Zhang W, Williams R, Rice WJ, Stokes DL, Zenklusen D, Chait BT, Sali A, Rout MP. Structure and Function of the Nuclear Pore Complex Cytoplasmic mRNA Export Platform. Cell 2016 Nov 17;167(5):1215-1228.e25
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Saroufim MA, Bensidoun P, Raymond P, Rahman S, Krause MR, Oeffinger M, Zenklusen D. The nuclear basket mediates perinuclear mRNA scanning in budding yeast. Journal of Cell Biology 2015 Dec 21;211(6):1131-40
- Castelnuovo M, Rahman S, Guffanti E, Infantino V, Stutz F and Zenklusen D. Single cell analysis reveals aspects of antisense RNA regulation and mode of action in PHO84 transcription repression. Nat Struct Mol Biol. 2013 Jul;20(7):851-8.
- Hocine S, Raymond P, Zenklusen D, Chao JA and Singer RH. Single-molecule analysis of gene expression using two-color RNA labeling in live yeast. Nature Methods 2013 Feb;10(2):119-21.
Disciplines
- Biochimie
- Génétique médicale
Champ d’expertise
- Expression et régulation génique
- Génétique moléculaire
- Mécanismes biologiques et biochimiques
- Signalisation cellulaire et cancer
- Cellule
- Imagerie (Outils de caractérisation)
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