David Bates, Ph.D.
Assistant Professor of Molecular and Human Genetics
Ph.D., University of New Mexico, 1998
Postdoc, University of New Mexico School of Medicine, 1999
Postdoc, Harvard University, 2006
Chromosome dynamics: Recent advances in fluorescence technologies have led to the discovery that bacterial chromosomes exist in an extremely precise spatial orientation within the confines of the cell, a trait formerly attributed only to eukaryotic chromosomes. This organization has profound influences on every synthetic event in the cell from DNA replication to gene expression. Moreover, in E. coli, following DNA replication, portions of sister chromosomes align at homologous sequences (cohesion) before separating en masse toward opposite poles. These and other findings illustrate striking similarities between how chromosomes are maintained in bacteria and eukaryotes. With this in mind, we view the E. coli chromosome as a “stripped-down” model of eukaryotic mitosis that will help reveal the underlying molecular mechanisms that drive chromosome behavior in all cells. My lab is developing a revolutionary fluorescence in situ hybridization (FISH) technique to examine the entire chromosome in a single cell by multi-color combinatorial labeling and computer separation of overlapping spectra. This method, inspired by chromosome painting techniques used in human chromosome karyotyping, allows us to visualize the position and orientation of the chromosome in three-dimensional space. Information from the FISH studies is then pooled with other assays including whole-genome microarray analysis of chromatin immunoprecipitates (ChIP-Chip) to map locations of chromosome structure proteins.
DNA Replication and cell cycle regulation: E. coli studies have provided a wealth of information on the biochemistry and genetics of DNA replication, and the basic replication machinery is highly conserved throughout all three domains of life. My lab is interested in the molecular mechanisms of DNA replication initiation and the transition between the replication origin bubble (open-complex) and association of the main replication machinery (replisome). These studies are made possible by a cell synchronization method that we developed, known as a baby cell machine. This technique generates large populations of unperturbed newborn cells that can be grown in unison, removed, and examined at any point in the cell cycle. Cell numbers are sufficient to support even very cell-demanding assays such as microarray analysis, not formerly possible with conventional synchronizing apparatuses. My lab is also exploring an exciting model of cell cycle control in which replication is coupled to cell division via a transitory physical linkage of the chromosome to the cell membrane at the site of cell division. Breakage of this linkage at the moment of cell birth would then in theory “license” a subsequent round of replication initiation.
Knowledge from the E. coli model will provide critical advances to our understanding of how defects in genome duplication and cell cycle control lead to human diseases including many types of cancers and congenital disorders. The superb manipulability of the bacterial system makes rapid advances possible.
- Joshi MC, Bourniquel A, Fisher J, Ho BT, Magnan D, Kleckner N, Bates D (2011). Escherichia coli sister chromosome separation includes an abrupt global transition with concomitant release of late-splitting intersister snaps. Proc. Natl. Acad. Sci. U S A 108(7): 2765-70. PubMed PMID: 21282646
- Fonville NC, Bates D, Hastings PJ, Hanawalt PC, Rosenberg SM (2010). Role of RecA and the SOS response in thymineless death in Escherichia coli. PLoS Genet. 6(3): e1000865. PubMed PMID: 20221259
- Stepankiw N, Kaidow A, Boye E, Bates D (2009). The right half of the Escherichia coli replication origin is not essential for viability, but facilitates multi-forked replication. Mol. Microbiol. 74(2): 467-79. PubMed PMID: 19737351
- Bates D (2008). The bacterial replisome: Back on track? Mol. Microbiol. 69(6): 1341-8. PubMed PMID: 18673457
- Bates D, Kleckner N (2005). Chromosome and Replisome Dynamics in E. coli: Loss of sister cohesion triggers global chromosome movement and mediates chromosome segregation. Cell 121(6): 899-911. PubMed PMID: 15960977
- Bates D, Epstein JA, Fahrner K, Berg H, Kleckner N (2005). The E. coli baby cell column: A novel cell synchronization method provides new insight into the bacterial cell cycle. Mol. Microbiol. 57(2): 380-91. PubMed PMID: 15978072
- Kasahara M, Clikeman JA, Bates D, Kogoma T (2000). RecA protein-dependent R-loop formation in vitro. Genes Dev. 14(3): 360-5. PubMed PMID: 10673507
- Asai T, Bates D, Boye E, Kogoma T (1998). Are minichromosomes valid model systems for DNA replication control? Lessons learned from Escherichia coli. Mol. Microbiol. 29(3): 671-5. PubMed PMID: 9723907
- Bates D, Boye E, Asai T, Kogoma T (1997). The absence of effect of gid or mioC transcription on the initiation of chromosomal replication in Escherichia coli. Proc. Natl. Acad. Sci. U S A 94(23): 12497-502. PubMed PMID: 9356478
- Bates D, Asai T, Cao Y, Chambers MW, Cadwell GW, Boye E, Kogoma T (1995). The DnaA box R4 in the minimal oriC is dispensable for initiation of Escherichia coli chromosome replication. Nucl. Acids Res. 23(16): 3119-25. PubMed PMID: 7667087
- Asai T, Bates D, Kogoma T (1994). DNA replication triggered by double-stranded breaks in E. coli: Dependence on homologous recombination functions. Cell 78(6): 1051-61. PubMed PMID: 7923355
David Bates, Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.
Phone: 713-798-8982 (lab) 713-798-7747 (office)