Heads of Laboratories

Sebastian Klinge, Ph.D.

Assistant Professor
Laboratory of Protein and Nucleic Acid Chemistry
klinge@rockefeller.edu

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Faculty Bio

Sebastian Klinge

Ribosomes, molecular machines that catalyze protein synthesis in cells, must be able to accurately and completely translate messenger RNA into synthesized proteins that function in all domains of life. Dr. Klinge is interested in the structure and function of the proteins required for the assembly of the eukaryotic ribosome. 

Ribosomes are giant molecular machines that are responsible for decoding the information contained in messenger RNA to synthesize proteins in all domains of life. Ribosome maturation, the process by which ribosomes are synthesized, is a very complex process, which involves approximately 200 factors in eukaryotes, of which most are essential for viability. These factors are involved in all stages of ribosome maturation, from transcription of ribosomal RNA in the nucleolus to export into the cytoplasm, where final stages of maturation occur. Our knowledge of the molecular machinery responsible for ribosome maturation is currently limited by a lack of structural information. Although work on the prokaryotic ribosome has advanced with structural studies of several important functional complexes, there had until recently been no atomic-level structural information about corresponding eukaryotic subunits. In contrast to their prokaryotic homologues, eukaryotic ribosomes are substantially larger, and this increase in size is accompanied by an overall increase in complexity. 

As a postdoc, Dr. Klinge solved the 3.5-Ångström crystal structure of the Tetrahymena thermophila 60S ribosomal subunit, the first atomic description of any large eukaryotic ribosomal subunit. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryote-specific ribosomal protein features and RNA expansion segments. Eukaryote-specific elements cluster in two regions of the solvent-exposed side. In contrast to the prokaryotic 50S subunit, in which ribosomal proteins are isolated entities, the 60S ribosomal proteins are largely interconnected, giving rise to an intricate network of interactions. Eukaryote-specific proteins frequently fulfill key structural roles by interacting with RNA expansion segments. The structure further reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site, since proteins in the vicinity of the catalytic center form an interconnected module.

At Rockefeller, Dr. Klinge works to solve the structures of macromolecular assemblies that catalyze key steps of ribosome maturation in eukaryotes. Structural information about these assemblies will represent a structural framework to understand the function of the complexes, and it will further provide a cornerstone for subsequent biochemical analysis.

Ultimately, Dr. Klinge hopes to reconstitute the initial stages of ribosome biogenesis in vitro. Such a system would facilitate the mechanistic study of different processing steps and allow for the isolation of specific intermediates, which cannot be obtained in vivo and may therefore provide novel approaches to study ribosome biogenesis.

CAREER

Dr. Klinge, a native of Germany, received his B.A. and Ph.D. in biochemistry from the University of Cambridge in 2005 and 2009, respectively. He was a postdoc in Nenad Ban’s laboratory at ETH Zurich in Switzerland from 2009 to 2013. He came to Rockefeller as assistant professor in 2013.

Dr. Klinge has been the recipient of fellowships from the Bill & Melinda Gates Foundation, the European Molecular Biology Organization and the Human Frontier Science Program. In 2014 Dr. Klinge was named a Human Frontier Science Program Career Development Awardee, an Alfred P. Sloan Research Scholar, an Irma T. Hirschl/Monique Weill-Caulier Trusts Research Awardee and a Rita Allen Foundation Scholar.



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