Three prestigious ERC grants go to LMU researchers
Peter Becker’s Project
In many organisms, the sexes differ in the set of chromosomes they possess. In the fruitfly Drosophila, females have two X chromosomes, while males have only one X. However, many of the genes on the X chromosome code for proteins that are essential for both sexes. To enable males to make these in the same amounts as females do, the single X works twice as hard as each X chromosome in female cells. This is achieved by a genetic mechanism called dosage compensation, which upregulates all the genes on the male X by a factor of two. Peter Becker and his team want to know how this vital process operates at the molecular level. In particular, they are interested in the role of the so-called "Dosage Compensation Complex" (DCC). The DCC is made up of a number of proteins and two non-coding RNAs, and plays a critical part in regulating gene activity on the X chromosome in male cells. Becker plans to investigate how the DCC is assembled, how it distinguishes the X from the other chromosomes, and how it binds to regulatory elements in all the genes on the single male X. The two RNAs that form part of the complex appear to be crucial for its function. “We want to take a closer look at their structures and identify their binding sites on the protein subunits of the complex,” says Becker. “We assume that the RNAs coordinate the assembly of the complex and then guide it to the chromosomal sites where it acts; they are responsible for the precise control of DCC’s function.” The team is now preparing to test this hypothesis, in the hope of understanding how dosage compensation, a highly specialized mechanism of gene regulation, actually works. Their findings may also have implications for the field of gene regulation in general.
Professor Peter Becker was born in 1958 in Frankfurt am Main. He studied Biology at Heidelberg University, obtaining his PhD in 1987. In 1988 he joined the staff of the German Center for Cancer Research in Heidelberg, where he had done his doctoral research. Following engagements at the Laboratory of Biochemistry at the National Cancer Institute (USA) and the European Molecular Biology Laboratory (EMBL) in Heidelberg, Becker was appointed to the Chair of Molecular Biology at the Adolf Butenandt Institute, which is part of the Faculty of Medicine at LMU. He is also a member of the Center for Integrated Protein Science Munich (CIPSM), a Cluster of Excellence at LMU. In 2005 Becker won the Gottfried Wilhelm Leibniz Prize awarded by the Deutsche Forschungsgemeinschaft (DFG).
Roland Beckmann’s Project
Ribosomes are the protein factories of the cell. These multimolecular complexes form the assembly lines at which thousands of amino acids are linked together, in sequences specified by coded blueprints called mRNAs, to form proteins with different functions. The goal of Beckmann‘s group is to elucidate the structure and function of these miniature machines. He and his colleagues use cryoelectron microscopy to visualize the fragile architecture of intact, fast-frozen ribosomes and investigate the structural changes that take place during the course of protein synthesis. The project selected for funding by the ERC will tackle both technical and biological problems. First, Beckmann’s team will explore ways of increasing the resolution of the imaging techniques, so that structural alterations can be discerned in much greater detail. A significant increase in resolution is necessary if one is to answer the biological questions of interest. Specifically, Beckmann wishes to study how proteins destined for integration into membranes are fed into them as they emerge from the ribosome during synthesis. To observe this process directly he attaches active ribosomes to tiny membrane disks held together by protein rings. He also wants to work out how the ribosome is released from the mRNA after the finished protein has been released, so that a new round of synthesis can begin. “It has only recently become clear that, in eukaryotic cells, an enzyme called ABCE1 is crucial for this process,” Beckmann says. His team hopes to visualize various ribosomal recycling intermediates containing bound ABCE1, with a view to understanding how this essential step in protein synthesis takes place.
Professor Roland Beckmann studied Biochemistry at the Free University in Berlin, obtaining his doctorate there in 1995. He then worked at Rockefeller University in New York (USA), before returning to Berlin in 2001 to lead a new research group set up at the Humboldt University with the support of the Volkswagen Foundation. In 2006 Beckmann accepted a professorship at the Chair of Biochemistry at LMU. Beckmann is also a member of the Center for Integrated Protein Science Munich (CIPSM), a Cluster of Excellence at LMU.
Hermann Gaub’s Project
Biofuels based on renewable raw materials offer a promising, climate-friendly alternative to fossil fuels, and are set to become more important as energy sources in the coming years. The use of organic waste or woody plants for energy production is an attractive proposition, because cultivation of such inedible materials does not entail competition with food production. The problem is that they contain large amounts of lignocellulose, a cross-linked biopolymer that is difficult to break down into components that can be used as biofuels. Therefore, the major hurdle that must be overcome before woody biomass can be used for fuel production is to find an efficient and economical way of degrading lignocellulose into polysaccharides. Only a few species of bacteria and fungi possess enzymes capable of doing this under natural conditions. Chemical degradation on an industrial scale requires a costly production process and the use of toxic reagents. In his ERC-funded project, biophysicist Hermann Gaub plans to design enzymes that are tailor-made for the efficient conversion of lignocellulose into polysaccharides. Gaub can manipulate molecules with the help of atomic force microscopy (AFM), picking them up and depositing them in defined positions with nanometer precision. He and his team will first mount lignocellulose-degrading enzymes obtained from various species on chips. They then plan to add particular nanocatalysts, producing artificial molecular complexes whose catalytic efficiency can be probed using fluorescence measurements. “The chip makes it possible to study at the level of single molecules, biological processes that normally take place inside cells,” says Gaub. The goal of the exercise is to find an optimal combination of enzyme and nanocatalyst, which would be suitable for use in an industrial setting.
Professor Hermann Gaub studied Physics at Ulm University and at the Technical University (TU) in Munich, where he earned his doctorate in 1984. He then carried out post-doctoral research at Stanford University (USA) and at the University of California in Santa Barbara. In 1992 Gaub took up a professorship at the TU Munich, and has held the Chair of Applied Physics at LMU since 1995. He was one of the founding members of the Center for NanoScience, and also belongs to the and also belongs to the Clusters of Excellence “Center for Integrated Protein Science Munich” (CIPSM) and “Nanosystems Initative Munich” (NIM).
ERC Advanced Investigator Grants
ERC Advanced Investigator Grants are designed to support highly innovative research, which has the potential to extend significantly the frontiers of existing fields and pioneer the investigation of new areas. Projects are assessed solely on the basis of the scientific stature of their authors and the originality and quality of the proposed research program.
Prof. Dr. Peter Becker
Adolf Butenandt Institute
Phone: +49 89 / 2180 - 75427
Fax: +49 89 / 2180 - 75425
Professor Peter Becker:
- Einsichten 2005:
Männliche Fliegen mit frisiertem Chromosom (von Susanne Wedlich; PDF, 84kb)
Professor Roland Beckmann:
- Press Release 11.10.2010:
“Don’t hesitate to interrupt ...” - How to gum up the ribosomal works
- Press Release 17.04.2011:
Crossing a soapy sea – 3D images reveal how proteins are inserted into the cell membrane
Professor Hermann Gaub:
- Press Release 13.11.2008:
The molecule factory of the future - self-assembling synthetic nanostructures