Faculty Profile: Albert Dahlberg, MD, PHD

Albert Dahlberg, MD, PHD
Professor of Medical Science
Molecular Biology, Cell Biology, & Biochemistry
Work: +1 401-863-2223
Understanding the mechanism of protein synthesis is the central focus of research in my laboratory. Our approach has involved the use of genetics, biochemistry and X-ray crystallography to correlate high resolution structures with function in mutant ribosomes.

Institutions

Bu

Research Description

Understanding the catalytic role of ribosomal RNA in protein synthesis was the central focus of my laboratory for a number of years. Our primary approach involved the use of genetic methods, specifically mutagenesis of plasmid-encoded rDNA. We investigated numerous regions of E. coli 16S and 23S rRNA to decipher both the higher order structure and the dynamic aspects of ribosome function.

More recently we have developed a similar genetic system in the extreme thermophile Thermus thermophilus and combined it with X-ray crystallography. We are now able to obtain high resolution crystal structures of mutant ribosomes as we probe sites involved in tRNA selection, translocation, peptide bond formation and signal transmission within and between the subunits. These same methods are being applied to investigate the mechanism of action and resistance of antibiotics affecting protein synthesis.

Grants and Awards

USPHS Predoctoral Fellow in combined M.D.-Ph.D. program, 1965-1967
University of Chicago, Chicago, Illinois

American Cancer Society Postdoctoral Fellow, 1970-1971
Aarhus University, Aarhus, Denmark

European Molecular Biology Organization, 1971-1972
Postdoctoral Fellow, Aarhus University, Aarhus, Denmark

NIH Research Career Development Award, 1975-1980

Teaching Award from Brown University Medical School, Class of 1980, 1980

Nominated for the Van Arkel Honorary Chair of Chemistry, 1985
Gorlaeus Laboratories, Department of Chemistry, State University of Leiden, The Netherlands

Who's Who in America, 44th edition, 1986

Visiting Professor, Institute of Microbiology, June-August 1988
University of Copenhagen, Denmark

Fellow, American Association for the Advancement of Science, 1992

Fellow, American Academy of Microbiology, 2000

Affiliations

1. American Society for Biochemistry and Molecular Biology
2. American Association for the Advancement of Science
3. American Society for Microbiology
4. Corporation of Haverford College, Haverford, PA

Funded Research

NIH GM19756-38 to 41: Polysomes and Subunits: Structure-Function
Relationships (2010-2014)
Annual Effort: 40%

Teaching Experience

Bio 127: Molecular biology, genetics and biochemistry of protein synthesis; from an historical perspective to the current atomic structures.
Bio 130: Biochemical review of DNA, RNA and protein synthesis, amino acid metabolism, and heme synthesis.
Currently on sababatic leave at the University of New South Wales, Sydney, Australia (Fall, 2006).

Courses Taught

  • Advanced Biochemistry (Bio 127)
  • Molecular and Regulatory Biochemistry (Bio 130)

Selected Publications

  • 16. Gregory ST, Dahlberg AE (2008) "Genetic and structural analysis of base substitutions in the central pseudoknot of Thermus thermophilus 16S ribosomal RNA". RNA,15:215-223. (2008)
  • 15. Kapralou S, Fabbretti A, Garulli C, Spurio R, Gualerzi CO, Dahlberg AE, Pon CL (2008) "Translational initiation factor IF1 of Bacillus Sterothermophilus and Thermus thermophilus substitute for Escherichia coli IF1 in vivo and in vitro without a direct IF1-IF2 interaction". Molec Microbiol, 70:1368-1377. (2008)
  • 13. Gregory ST, Dahlberg AE (2008) "Transposition of an insertion sequence, ISTth7, in the genome of the extreme thermophile Thermus thermophilus HB8". FEMS Microbiol Lett, 289: 187-192. (2008)
  • 12. Demirci, H., Gregory, S., Dahlberg, A. and G. Jogl (2008) "Crystal structure of the Thermus thermophilus 16S rRNA methyltransferase RsmC in complex with cofactor and substrate guanosine". J. Biol. Chem., 283: 26548-26556. (2008)
  • 11. Gregory, S., Carr, J. and A. Dahlberg (2008) "A signal relay between ribosomal protein S12 and elongation factor Tu during decoding of mRNA". RNA, 15:208-214. (2008)
  • 10. Rodriguez-Correa, D. and A. Dahlberg (2008) "Kinetic and thermodynamic studies of peptidyltransferase in ribosomes from the extreme thermophile Thermus thermophilus". RNA, 14:2314-2318. (2008)
  • 8. Demirci, H., Gregory, S., Dahlberg, A. and G. Jogl (2008) "Multiple-site trimethylation of ribosomal protein L11 by the PrmA methyltransferase", Structure. 16:1059-1066. (2008)
  • 9. Brandi, L., Fabbretti, A., Pon, C., Dahlberg, A. and C. Gualerzi (2008) "Initiation of protein synthesis: A target for antimicrobials". Expert Opin Ther Targets, 12:519-534. (2008)
  • 14. Monshupanee T, Gregory ST, Douthwaite S, Chungjatupornchai W, Dahlberg AE (2008) "Mutations in the conserved helix 69 of 23S rRNA of Thermus thermophilus that affect capreomycin resistance but not posttranscriptional modifications". J Bacteriol, 190:7754-7761. (2008)
  • 7. Demirci, H., Gregory, S., Dahlberg, A. and G. Jogl (2007) "Recognition of ribosomal protein L11 by the protein trimethyltransferase PrmA". EMBO J. 26:567-577. (2007)
  • 6. Schuwirth, B., Day, J., Hau, C., Janssen, G., Dahlberg, A., Doudna Cate, J. and A. Vila-Sanjurjo (2006) "Structural analysis of kasugamycin inhibition of translation". Nat. Str. & Mol. Biol. 13:879-886. (2006)
  • 5. Carr, J., D-M. Hamburg, S. Gregory, P. Limbach and A. Dahlberg (2006) "Effects of streptomycin resistance mutations on posttranslational modification of ribosomal protein S12". J. Bacteriol. 188:2020-2023. (2006)
  • 4. Gregory, S., J. Carr, D. Rodriguez-Correa and A. Dahlberg (2005) "Mutational analysis of 16S and 23S rRNA genes of Thermus thermophilus". J. Bacteriol. 187:4804-4812. (2005)
  • 3. Suh, M.-J., D.-M. Hamburg, S. Gregory, A. Dahlberg and P. Limbach (2005) "Extending ribosomal protein identifications to unsequenced bacterial strains using matrix-assisted laser desorption/ionization mass spectrometry" Proteomics. 5:4818-4831. (2005)
  • 2. Carr, J., S. Gregory and A. Dahlberg (2005) "Severity of the streptomycin-resistance and streptomycin-dependence phenotypes of ribosomal protein S12 of Thermus thermophilus depends on the identity of highly conserved amino acid residues". J. Bacteriol.187:3548-3550. (2005)
  • 1. Gregory, S., J. Carr and A. Dahlberg (2005) "A mutation in the decoding center ofThermus thermophilus 16S rRNA suggests a novel mechanism of streptomycin resistance". J. Bacteriol. 187:2200-2202. (2005)