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James M. Berger

James C. Barrow
Department Affiliation: Primary: Biophysics and Biophysical Chemistry; Secondary: Pharmacology and Molecular Sciences; Oncology
Degree: Ph.D., Harvard University
Rank: Professor
Telephone Number: 410-955-7163
Fax Number: 410-955-0637
E-mail address: jmberger@jhmi.edu
School of Medicine Address: Wood Basic Science 713,
725 N. Wolfe Street, Baltimore, MD  21205
 
Website:  http://berger.med.jhmi.edu/

Structural and catalytic mechanisms of nucleic-acid machines and assemblies; control of DNA replication and chromosome superstructure; small-molecule and biological regulatory mechanisms.

Research in my laboratory is focused on understanding the molecular mechanisms and cellular functions of multisubunit assemblies that control the organization, preservation, and flow of genetic information. We are particularly interested in developing real-time, atomic-level models that explain how chemical energy is transduced into force and motion, and how dynamic assemblies control DNA replication, gene expression, chromosome superstructure, and other essential nucleic-acid transactions.

My group’s approach relies on a blend of structural, biochemical, and biophysical methods to define the architecture, function, evolution, and regulation of biological complexes. X-ray crystallography and traditional biochemistry have traditionally formed the core of our approach; however, we are increasingly merging these methods with other experimental tools such as small-angle X-ray scattering, single-molecule studies, and electron microscopy. Since the inception of the group in 1995, we have biochemically and structurally defined the range and nature of key functional intermediates and transitions for a variety of nucleotide-dependent ‘molecular machines,’ including topoisomerases, helicases, condensins, and replication initiation complexes.

Our efforts have allowed us to define how biological systems use these factors to organize, transport, and reshape target nucleic-acid substrates at a physical level, and how their actions are controlled by both protein-protein interactions and small-molecule agents. My lab has a consistent track record of bringing new concepts and fundamentally important discoveries to the field, and in innovating new approaches and technologies to studying multi-protein and protein/nucleic-acid assemblies in general. Training has been a similarly important facet of my efforts; to date, 22 doctoral students and 20 post-doctoral fellows have worked in my group. All who have left thus far have gone on to productive careers in academia (18), biotechnology/pharma (10), law (2), medicine (1), and consulting (1).

A complete list of our publications, excluding chapters and articles not accessed by PubMed, can be found at: http://www.ncbi.nlm.nih.gov/sites/myncbi/james.berger.1/bibliograpahy/40436728/public/?sort=date&direction=descending.

 

Representative Publications:  

  • Lawson M.R., Dyer, K., Berger, J.M. Ligand-induced and small-molecule control of substrate loading in a hexameric helicase. Proc Natl Acad Sci U S A. 2016 Nov 29;113(48):13714-13719. Pub Med Reference
     
  • Hood, I.V., Berger, J.MElife. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication. 2016 May 31;5. pii: e14158. doi: 10.7554/eLife.14158. Pub Med Reference
     
  • Blower, T.R., Williamson, B.H., Kerns, R.J., Berger, J.M. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1706-1713. Pub Med Reference
     
  • Arias-Palomo, E., Berger, J.M. An Atypical AAA+ ATPase Assembly Controls Efficient Transposition through DNA Remodeling and Transposase Recruitment. Cell. 2015 Aug 13;162(4):860-871. Pub Med Reference
     
  • Bleichert, F., Botchan, M.R., Berger, J.M. Crystal structure of the eukaryotic origin recognition complex. Nature. 2015 Mar 19;519(7543):321-326. Pub Med Reference

     

  • Costa, A., Renault, L., Swuec, P., Petojevic, T., Pesavento, J.J., Ilves, I., MacLellan-Gibson, K., Fleck, R.A., Botchan, M.R., Berger, J.M. DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome. Elife. 2014 Aug 12;3:e03273. Pub Med Reference
     
  • Drlica, K., Mustaev, A., Towle, T.R., Luan, G., Kerns, R.J., Berger, J.M. Bypassing fluoroquinolone resistance with quinazolinediones: studies of drug-gyrase-DNA complexes having implications for drug design. ACS Chem Biol. 2014 Dec 19;9(12):2895-2904. Pub Med Reference
     

 



Other graduate programs in which Dr. Berger participates: