Project

Back to overview

Bonus of Excellence - Structural studies of complexes involved in ribosome assembly and translation initiation in yeast

English title Bonus of Excellence - Structural studies of complexes involved in ribosome assembly and translation initiation in yeast
Applicant Ban Nenad
Number 163478
Funding scheme Project funding
Research institution Institut für Molekularbiologie und Biophysik Deptartement für Biologie ETH Zurich
Institution of higher education ETH Zurich - ETHZ
Main discipline Molecular Biology
Start/End 01.11.2015 - 31.10.2018
Approved amount 930'138.00
Show all

All Disciplines (2)

Discipline
Molecular Biology
Biochemistry

Keywords (3)

Ribosome; Initiation; Translation

Lay Summary (German)

Lead
Proteine werden in allen Organismen durch Ribosomen synthetisiert, welche anhand einer mRNA-Vorlage den genetischen Code in eine Aminosäurekette übersetzen. Das Ribosom ist eine grosse molekulare Maschine und besteht aus mehreren rRNAs und Proteinen. Die in der mRNA gespeicherte Information wird durch die kleine ribosomale Untereinheit entschlüsselt, während die grosse Untereinheit die Bildung der Peptidbindung katalysiert. Obwohl die grundlegenden Prozesse der Proteinbiosynthese bei allen Lebensformen gleich sind, sind die regulatorischen Mechanismen bei Eukaryoten wesentlich komplexer als bei Bakterien, was sich in der Grösse der Ribosomen wiederspiegelt. Weiter hängt bei eukaryotischen Ribosomen der richtige Zusammenbau dieser molekularen Maschinerie von zahlreichen akzessorischen Proteinen ab, und für die Initiation der Translation werden wesentlich mehr unterschiedliche Initiationsfaktoren benötigt.
Lay summary

Das Hauptziel der Forschung in unserem Labor ist die Strukturanalyse von prokaryotischen und eukaryotischen Ribosomen, deren Untereinheiten sowie deren Komplexe mit verschiedenen regulatorischen Faktoren, um detaillierte Einblicke in die Proteinbiosynthese zu erhalten. Dazu verwenden wir als primäre Methode die Kristallografie, in Kombination mit Elektronenmikroskopie und Biochemie.

Mittels finanzieller Unterstützung durch den SNF beabsichtigen wir, die Ribosomen-Biogenese in Hefe genauer zu untersuchen. Dazu sollen Komplexe mit den involvierten akzessorischen Proteinen analysiert werden, mit Fokus auf die Vorgänge in der grossen eukaryotischen 60S Untereinheit. Des Weiteren wollen wir die Mechanismen der Translations-Initiation und Re-Initiation, welche bei speziellen zellulären mRNAs vorkommt, unter die Lupe nehmen.


 

Direct link to Lay Summary Last update: 02.11.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Conformational Switching of the Nuclear Exosome during Ribosome Biogenesis
Kummer Eva, Ban Nenad (2018), Conformational Switching of the Nuclear Exosome during Ribosome Biogenesis, 57(32), 4765-4766, American Chemical Society, USA 57(32), 4765-4766.
The Complete Structure of the Mycobacterium smegmatis 70S Ribosome
Hentschel Jendrik, Burnside Chloe, Mignot Ingrid, Leibundgut Marc, Boehringer Daniel, Ban Nenad (2017), The Complete Structure of the Mycobacterium smegmatis 70S Ribosome, in Cell Reports, 20(1), 149-160.
Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon
Jomaa Ahmad, Boehringer Daniel, Leibundgut Marc, Ban Nenad (2016), Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon, in Nature Communications, 7(1), 10471-10471.
Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates
Bar-Yaacov Dan, Frumkin Idan, Yashiro Yuka, Chujo Takeshi, Ishigami Yuma, Chemla Yonatan, Blumberg Amit, Schlesinger Orr, Bieri Philipp, Greber Basil, Ban Nenad, Zarivach Raz, Alfonta Lital, Pilpel Yitzhak, Suzuki Tsutomu, Mishmar Dan (2016), Mitochondrial 16S rRNA Is Methylated by tRNA Methyltransferase TRMT61B in All Vertebrates, in PLOS Biology, 14(9), e1002557-e1002557.
Structure and Function of the Mitochondrial Ribosome
Greber Basil J., Ban Nenad (2016), Structure and Function of the Mitochondrial Ribosome, in Annual Review of Biochemistry, 85(1), 103-132.
Insertion of the Biogenesis Factor Rei1 Probes the Ribosomal Tunnel during 60S Maturation
Greber Basil Johannes, Gerhardy Stefan, Leitner Alexander, Leibundgut Marc, Salem Michèle, Boehringer Daniel, Leulliot Nicolas, Aebersold Ruedi, Panse Vikram Govind, Ban Nenad (2016), Insertion of the Biogenesis Factor Rei1 Probes the Ribosomal Tunnel during 60S Maturation, in Cell, 164(1-2), 91-102.
Architecture of human mTOR complex 1
Aylett C. H. S., Sauer E., Imseng S., Boehringer D., Hall M. N., Ban N., Maier T. (2015), Architecture of human mTOR complex 1, in Science, 351(6268), 48-52.

Collaboration

Group / person Country
Types of collaboration
Timm Maier / University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Vikram Panse / University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Mike Hall / University of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Daniel Mishmar / Ben-Gurion University of the Negev Israel (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Andre Schneider / University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Shu-ou Shan / Caltech United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Andrej Sali / University of San Francisco United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Ruedi Aebersold / ETH Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Albert Heck Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
RNA Symposium: Regulatory circuits in RNA biology Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins 17.10.2018 Vienna, Austria Ban Nenad;
Two Days of Proteostasis in Konstanz Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins” 11.10.2018 Konstanz, Germany Ban Nenad;
2018 Louis-Jeantet Symposium Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins 08.10.2018 Geneva, Switzerland Ban Nenad;
27th tRNA conference Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins 23.09.2018 Strasbourg, France Ban Nenad;
Summer School of Biophysics Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins 28.08.2018 Split, Croatia Ban Nenad;
Gordon Research Conference 2018 Three Dimensional Electron Microscopy Poster Analysis of coupled conformational changes in the biogenesis of the eukaryotic 40S ribosomal subunit 03.06.2018 Newport, United States of America Böhringer Daniel;
38th Blankenese Conference Talk given at a conference Protein synthesis: from ribosome assembly to targeting of membrane proteins 05.05.2018 Hamburg, Germany Ban Nenad;
Otto Naegeli Prize Ceremony Individual talk Unique Features of Eukaryotic Ribosomes 10.04.2018 Zurich, Switzerland Ban Nenad;
Grenoble EMBL Seminar Series Individual talk Structures of Prokaryotic and Eukaryotic Ribosomal Complexes Involved in Initiation, Maturation and Targeting of Proteins to Membranes 11.01.2018 Grenoble, France Ban Nenad;
Downing College 11-13th Dec - New approaches for investigating nascent peptide folding Talk given at a conference Structures of Prokaryotic and Eukaryotic Ribosomal Complexes Involved in Initiation, Maturation and Targeting of Proteins to Membranes 11.12.2017 Cambridge, United States of America Ban Nenad;
Technical University Darmstadt Individual talk Extensions, extra factors and extreme complexity: Ribosomal structures provide insights into eukaryotic translation 14.11.2017 Darmstadt, Germany Ban Nenad;
Gordon Research Conference 2017 Three Dimensional Electron Microscopy Poster Variance analysis of cryo-EM 3D reconstructions 06.11.2017 Les Diablerets, Switzerland Böhringer Daniel;
SFB Symposium "The biology of RNA-protein interactions" Talk given at a conference Extensions, extra factors and extreme 11.10.2017 Regensburg , Germany Ban Nenad;
German Society of Chemistry Scientific Forum Chemistry 2017 - Anniversary Congress - 150 Years: Session: Molecules of Life - Molecules in Life Talk given at a conference Keynote lecture: Beyond the Prokaryotic Ribosome: Structural and Functional Insights into Eukaryotic and Mitochondrial Ribosomes 10.09.2017 Berlin, Germany Ban Nenad;
NCCR RNA & Disease Summer School Talk given at a conference Cryo-electron microscoopy 28.08.2017 Saas Fee, Switzerland Böhringer Daniel;
NCCR RNA and disease summer school Talk given at a conference Beyond the Prokaryotic Ribosome: Structural and Functional Insights Into Eukaryotic and Mitochondrial Ribosomes 28.08.2017 Saas Fee, Switzerland Ban Nenad;
Microscopy Conference 2017 Talk given at a conference Variance analysis of cryo-EM 3D reconstructions 21.08.2017 Lausanne, Switzerland Böhringer Daniel;
10th Joint Meeting on Medicinal Chemistry Talk given at a conference Beyond the Prokaryotic Ribosome: Structural and Functional Insights Into Eukaryotic and Mitochondrial Ribosomes 25.06.2017 Dubrovnik, Croatia Ban Nenad;
EMBO lecture course: Integrative Structural Biology Talk given at a conference Protein synthesis by large cellular assemblies 02.06.2017 Erice, Italy Ban Nenad;
Ernst Jung Prize symposium Talk given at a conference Structural and functional insights into eukaryotic and mitochondrial ribosomes 18.05.2017 Hamburg, Germany Ban Nenad;
EMBO conference: Towards Novel Therapies: Emerging Insights from Structural and Molecular Biology Talk given at a conference Beyond the prokaryotic 06.03.2017 Groningen, Netherlands Ban Nenad;
Molecular Machines: integrative Structural and Molecular Biology Talk given at a conference Using interdisciplinary approaches in structural biology to investigate initiation and regulation of translation in eukaryotes 20.11.2016 Heidelberg, Germany Ban Nenad;
Centro Nacional de Biotecnología: University Seminar Series Individual talk Beyond the prokaryotic ribosome 11.11.2016 Madrid, Spain Ban Nenad;
Centre for Biological Research, Spanish National Research Council: University Seminar Series Individual talk Beyond the prokaryotic ribosome 11.11.2016 Madrid, Spain Ban Nenad;
Basel Life Science Week Talk given at a conference Beyond the prokaryotic ribosome 19.09.2016 Basel, Switzerland Ban Nenad;
13th Horizons in Molecular Biology Talk given at a conference Beyond the prokaryotic ribosome 12.09.2016 Goettingen, Germany Ban Nenad;
13th International School of Biophysics Talk given at a conference Ribosomes and their functional complexes 01.09.2016 Zadar, Croatia Ban Nenad;
13th International School of Biophysics Talk given at a conference Beyond the prokaryotic ribosome 01.09.2016 Zadar, Croatia Ban Nenad;
EMBO conference: Ribosome Structure and Function Talk given at a conference Beyond the prokaryotic ribosome: structural and functional insights into eukaryotic and 06.07.2016 Strasbourg, France Ban Nenad;
EMBO Conference: Mitochondrial Molecular Biology Talk given at a conference Beyond the prokaryotic ribosome: structural and functional insights into eukaryotic and mitochondrial translation 19.06.2016 Stockholm, Sweden Ban Nenad;
Hybrid Methods Symposium Talk given at a conference Using interdisciplinary approaches in structural biology to investigate initiation of translation in eukaryotes 21.03.2016 Villigen, Switzerland Ban Nenad;
University seminar series Individual talk Beyond the prokaryotic ribosome: structural and functional insights into eukaryotic and mitochondrial ribosomes 04.02.2016 Cambridge , United States of America Ban Nenad;
Inter-University seminar series Individual talk Beyond the prokaryotic ribosome: structural and functional insights into eukaryotic and mitochondrial ribosomes 02.02.2016 Potsdam, United States of America Ban Nenad;
Clarkson University Distinguished Speaker “Shipley” Lecture Individual talk Visualizing the invisible 02.01.2016 Potsdam, United States of America Ban Nenad;


Communication with the public

Communication Title Media Place Year
Print (books, brochures, leaflets) Ribosomen der Eukaryonten: molekulare Maschinen mit besonderen Eigenschaften Western Switzerland German-speaking Switzerland 2018

Awards

Title Year
Human Frontiers Science Program Long Term Fellowship 2018
Otto Naegeli Prize for Medical Research 2018
EMBO fellowship 2017
Ernst Jung Prize for Medicine 2017
FEBS fellowship 2017
Shipley Distinguished Lectureship 2016

Associated projects

Number Title Start Funding scheme
144214 Structural studies of eukaryotic complexes involved in ribosome assembly and translation initiation 01.11.2012 Project funding
141735 NCCR RNA & disease: Understanding the role of RNA biology in disease mechanisms (phase I) 01.05.2014 National Centres of Competence in Research (NCCRs)
144214 Structural studies of eukaryotic complexes involved in ribosome assembly and translation initiation 01.11.2012 Project funding
182341 Structural studies of eukaryotic ribosomal complexes involved in regulation of translation and in mitochondrial protein synthesis 01.11.2018 Project funding
170808 Acquisition of a Talos Arctica transmission electron microscope for single particle analysis and cryo-tomography 01.05.2017 R'EQUIP

Abstract

Ribosomes are responsible for mRNA directed protein synthesis in all organisms. Bacterial ribosomes are complex ribonucleoprotein assemblies that have molecular weights of approximately 2.5 million Daltons and contain 50-60 different protein molecules and three different RNAs. Eukaryotic ribosomes are approximately 30% larger than their bacterial counterparts with a molecular weight of at least 3.3 MDa (yeast). Although basic aspects of protein synthesis are preserved in all kingdoms of life, there are many important differences between bacterial and eukaryotic ribosomes and their roles in translation. Consequently, eukaryotic ribosomes require a large number of assembly and maturation factors during their biogenesis, they use numerous initiation factors, and are subjected to extensive regulation. The main goal of the research in my laboratory supported through Swiss National Science Foundation is to study structures of prokaryotic and eukaryotic ribosomes, ribosomal subunits and their complexes with various factors involved in protein synthesis. In our research we use a combination of biochemistry, crystallography and electron microscopy experiments. As evidenced by the list of recent publications from my lab we have accumulated the expertise and established the methodology to competitively conduct research in this field. As a continuation of our research on eukaryotic ribosomes we intend to study the mechanisms of ribosome assembly in yeast and the factors involved in this process, with a particular emphasis on the maturation of the eukaryotic 60S ribosomal subunit. Furthermore, we intend to investigate the mechanisms of translation initiation and reinitiation by special cellular messenger RNAs. Our recent results, obtained during the previous phase of this grant support, will provide the basis for this application.
-