FOR 1805:  Ribosome Dynamics in Regulation of Speed and Accuracy of Translation

• Subject Area: Biology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 207100805

Translation of the genetic information from a nucleotide sequence into a functional protein is a central biological process. The aim of this Research Unit is to uncover dynamic aspects of the ribosome function in translation on different levels, from atomic analysis to a global-scale stochastic behaviour. Both, prokaryotic and eukaryotic systems will be used as research objects, which will provide invaluable insights into common principles and divergent features in translation dynamics and regulation across the species. We will use a combination of interdisciplinary approaches, including high-resolution structural studies (single and multi-particle cryo-EM and X-ray crystallography), biophysical (kinetics, molecular dynamics simulation, stochastic modelling), and biochemical (quantitative mass spectrometry, ribosomal profiling probed with the power of highly parallel deep sequencing) approaches. The team we have assembled consolidates the scientific expertise across Germany on ribosome function and protein translation to unravel molecular details on (1) the role of various translation factors on the metastable energy landscape of the translating ribosome, (2) the speed and accuracy in translation of single codon and whole open-reading frame, (3) the impact of external factors (antibiotics, environmental stress) on translation fidelity and processivity, and (4) the link between translation and protein assembly and function. On a long-term scale, we believe that merging the research activities with a focus on the ribosome, as crucial molecular machinery for the cell, will provide unprecedented insights into central molecular aspects of the ribosome function and dynamics, ultimately enabling us to generate an integrated view of the molecular choreography of the processes orchestrated by the ribosome.

• DFG Programme: Research Units

Projects

• Coordination of the Research Unit 1805 (Applicant Ignatova, Zoya )
• Coordination of translation and assembly of protein complexes (Applicant Kramer, Günter )
• Dynamic interplay between chloramphenicol/linezolid and the translating ribosome (Applicant Wilson, Daniel Nicodemus )
• Dynamics of translation under normal conditions and oxidative stress (Applicant Ignatova, Zoya )
• Mechanisms regulating speed and accuracy of translation (Applicants Rodnina, Marina V. ;  Wohlgemuth, Ingo )
• Probing the mechanisms of unnatural protein translation with an engineered genetic code and orthogonal translational pairs (Applicants Budisa, Nediljko ;  Vaiana, Andrea C. )
• Stochastic modelling of protein synthesis by ribosomes (Applicant Lipowsky, Reinhard )
• Structural basis of canonical and non-canonical translation termination and recycling by eRF1/eRF3 and ABCE1 in yeast and humans (Applicant Beckmann, Roland )
• Structural studies of ribosome-SelB complexes and ribosome nascent chain folding intermediates by cryo-EM and molecular dynamics simulations (Applicants Grubmüller, Helmut ;  Stark, Holger )
• Translational GTPases and the energy landscape of the 70S ribosome (Applicant Spahn, Christian M. T. )

• Spokesperson: Professorin Dr. Zoya Ignatova