Microbial Genetics and Plasmid Biology

Research interests

Research in this laboratory has its roots in the study of the E. coli plasmid ColE1 and the mechanisms which ensure its efficient transmission to daughter cells at division. This has developed into a study of how ColE1 controls the fundamental cellular processes of replication, site-specific recombination and cell division to ensure its own survival. These questions are explored using conventional genetic and biochemical approaches, and also through the application of control engineering principles in a systems biology analysis of plasmid behaviour. In parallel we pursue the application of our discoveries to improve the productivity and utility of the bacterial cell factory.

Plasmids and the control of the bacterial cell cycle

The formation of plasmid dimers and higher multimers reduces plasmid copy number and interferes with their stable inheritance. The nucleoprotein complex which assembles at the cer site of plasmid ColE1 mediates the restoration of dimers to monomers by site-specific recombination. However, this is far from being the whole story. The same complex also initiates a signaling process via a small, non-coding RNA which results in the co-ordinated inhibition of plasmid replication and cell division while dimer resolution is in progress. A focus of our current work is to discover the precise mechanisms by which proteins with key roles in these processes are controlled.

Applied research

The laboratory is involved in the commercialization of discoveries arising from our basic research program through the spin-off company Cambridge Microbial Technologies. The main achievement has been the development of the Quiescent Cell Expression System (Q-Cells), a novel bacterial cell factory for the expression of recombinant proteins in non-growing E. coli.

Key publications

1. Chimerel, C., Field, C.M., Pinero-Fernandez, S., Keyser, U.F., and Summers, D.K. (2012). Indole prevents Escherichia coli cell division by modulating membrane potential. Biochimica et Biophysica Acta 1818, 1590-1594
2. Field, C.M., and Summers, D.K. (2011). Multicopy plasmid stability: Revisiting the dimer catastrophe. J Theor Biol 291, 119-127
3. Pinero-Fernandez, S., Chimerel, C., Keyser, U.F., and Summers, D.K. (2011). Indole transport across Escherichia coli membranes. Journal of Bacteriology 193: 1793-1798
4. Summers, D. K. and Chant, E. (2010). Chemical induction in quiescence in bacteria. USPTO. United States Patent number 7,790,435
5. Blaby, I.K. and Summers, D.K. (2009) The role of FIS in the Rcd checkpoint and stable maintenance of plasmid ColE1. Microbiology 155: 2676-2682
   
6. Chant, E.L., and Summers, D.K. (2007) Indole signalling contributes to the stable maintenance of Escherichia coli multicopy plasmids. Molecular Microbiology 63: 35-43
7. Balding, C., Blaby, I. and Summers, D. (2006) A mutational analysis of the ColE1-encoded cell cycle regulator Rcd confirms its role in plasmid stability. Plasmid 56: 68-73
8. Mukherjee, K. J., Rowe, D.C.D., Watkins, N.A. and Summers D.K. (2004) Studies on Single Chain Antibody Expression in Quiescent Escherichia coli. Applied and Environmental Microbiology 70: 3005-3012

Page updated 14 May 2012