Download Dr. Anton Meinhart Department of Biomolecular

Dr. Anton Meinhart
Department of Biomolecular Mechanisms
Max Planck Institute for Medical Research
69120 Heidelberg, Germany
Phone: +49-(0)6221-486505
Fax: +49-(0)6221-486585
E-mail: [email protected]
28/04/1974 Wels, Austria
CURRICULUM VITAE
2006 - present
Research group leader, Max Planck Institute for Medical Research,
Heidelberg
2004 - 2006
Project and group leader, Max Planck Institute for Medical
Research, Heidelberg
2002 - 2004
PostDoc, Gene Center, University of Munich
2001 - 2002
PostDoc, Free University of Berlin
1999 - 2001
Ph.D., Free University of Berlin
1997 - 1998
Diploma thesis, Crystallography, University of Vienna, Austria and
University of Cologne
1993 - 1997
Study of Mineralogy and Crystallography, University of Vienna,
Austria
HONORS AND FELLOWSHIPS
2003 - 2004
EMBO long term fellowship
1999
Young Scientist Award from the Faculty of Natural Science,
University of Vienna
1997 - 1998
DAAD-Fellowship, Student exchange program
FIELDS OF INTEREST
Structure – Function relationship of RNA processing factors; Coupling of Processing
machines in RNA maturation; Bacterial Toxin Antitoxin systems
CURRENTLY FUNDED PROJECTS
DFG Einzelantrag ME 3135/1-2
EXPERIENCE IN SUPVERSION OF DOCTORIAL CANDIDATES:
Currently advisor of 2 Ph.D. thesis
PUBLICATIONS (10 most important publications):
Vasiljeva, L., Kim, M., Mutschler, H., Buratowski, S., and Meinhart, A. (2008). The Nrd1Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA
polymerase II C-terminal domain. Nat. Struct. Mol. Biol. 15:795-804.
Becker, R., Loll, B., and Meinhart, A. (2008). Snapshots of the RNA processing factor
SCAF8 bound to different phosphorylated forms of the carboxy-terminal
domain of RNA-polymerase II. J. Biol. Chem. 283:22659-22669.
Khoo, S. K., Loll, B., Chan, W. T., Shoeman, R. L., Ngoo, L., Yeo, C. C., and Meinhart,
A. (2007). Molecular and structural characterization of the PezAT
chromosomal toxin-antitoxin system of the human pathogen Streptococcus
pneumoniae. J. Biol. Chem. 282:19606-19618.
Meinhart, A., Kamenski, T., Hoeppner, S., Baumli, S., and Cramer, P. (2005). A
structural perspective of CTD function. Genes Dev. 19:1401-1415.
Armache, K. J., Mitterweger, S., Meinhart, A., and Cramer, P. (2005). Structures of
complete RNA polymerase II and its subcomplex, Rpb4/7. J. Biol. Chem.
280:7131-7134.
Kamenski, T., Heilmeier, S., Meinhart, A., and Cramer, P. (2004). Structure and
mechanism of RNA polymerase II CTD phosphatases. Mol. Cell 15:399-407.
Meinhart, A., and Cramer, P. (2004). Recognition of RNA polymerase II carboxy-terminal
domain by 3'-RNA-processing factors. Nature 430:223-226.
Meinhart, A., Silberzahn, T., and Cramer, P. (2003). The mRNA transcription/processing
factor Ssu72 is a potential tyrosine phosphatase. J. Biol. Chem. 278:1591715921.
Meinhart, A., Blobel, J., and Cramer, P. (2003). An extended winged helix domain in
general transcription factor E/IIE alpha. J. Biol. Chem. 278:48267-48274.
Meinhart, A., Alonso, J. C., Strater, N., and Saenger, W. (2003). Crystal structure of the
plasmid maintenance system epsilon/zeta: functional mechanism of toxin zeta
and inactivation by epsilon 2 zeta 2 complex formation. Proc. Natl. Acad. Sci.
USA 100:1661-1666.
RESEARCH INTEREST
Macromolecular Machines in eukaryotic RNA 3’-end Processing
Concomitant with eukaryotic transcription, RNA undergoes extensive modification. Nuclear
processes, such as capping, splicing and cleavage / polyadenylation are necessary for
producing a mature RNA. These RNA processing events take place in a dynamic interplay of
individual transcription and processing complexes within the transcription machinery and they
are intimately coupled with each other. Whereas the general protein composition and structures
of individual domains of RNA 3’-end processing factors have been elucidated, information on the
three dimensional arrangements within these machines, the understanding of complex formation
and the spatial and temporal coordination of these events is very limited.
Our current focus is a comprehensive structural and biophysical / biochemical characterization of
one of the key components of the RNA 3’-end processing machinery in Saccharomyces
cerevisiae, the cleavage factor IA (CF IA). CF IA governs the spatial and temporal coordination
of mRNA 3’-end processing, since it recruits the entire machinery to the site of transcription by
binding to the RNA Polymerase II and is thought to recognize signal sequences at the nascent
RNA. We are currently studying the assembly pathway of CF IA and want to obtain structural
information of this complex to the highest resolution possible. Additionally, we are interested in
the putative enzymatic polynucleotide kinase activity of CF IA and its impact on complex
formation or disassembly. Ultimately, these investigations will provide new insights in how and
when this complex is formed during transcription and how sequence specificity for the RNA is
achieved.
In a long term perspective, we will extend our investigations on macromolecular assemblies that
are involved in 3’-end processing events of snRNA and snoRNA and cryptic unstable transcripts
(CUTs) and transcription termination. These projects are already initiated and we have
characterized how the physical link between these machines and RNA polymerase II is
established. In near future we will concentrate on the entire complexes and study their structural
arrangement and the kinetics of assembly and disassembly.
Macromolecular Machines in bacterial genome stabilization.
The second research focus is the structural and functional characterization of bacterial toxin and
antitoxin systems. Bacterial Toxin-Antitoxin (TA) systems were initially discovered as genetic
elements encoded from prokaryotic low-copy number plasmids, where they are involved in
stable maintenance and inheritance of these mobile genetic elements. Stable maintenance is
performed by a mechanism called postsegregational killing (PSK), where libration of the
bacterial toxin from its cognate antitoxin eventually leads to cell death, once an offspring has lost
the plasmid.
These systems are of general interest for antimicrobial therapy, since any activation of these
toxic proteins eventually leads to cell death. We are currently investigating the kinetics of
assembly and disassembly pathway of the PezA/PezT system, which we have recently
discovered to be encoded from the genome of the human pathogen Streptococcus pneumoniae.
The second important scope of this project is to elucidate the still enigmatic toxic activity of this
system in order to find ways of activating or deactivating this system with the ultimate goal of
antimicrobial therapy.
METHODS APPLIED
Protein crystallography, Various biophysical techniques: Fluorescence spectroscopy, Isothermal
titration Calorimetry, Circular dichroism spectroscopy, Analytical Ultracentrifugation, Dynamic
Light Scattering etc., Protein chemistry, Classical Molecular Biology (E. coli, Insect cell culture
and yeast);