Department of Biological Science
National University of Singapore
14 Science Drive 4
Molecularbasis for bacterial pathogenesis
DNA and protein delivery systems
Vectors for gene therapy and DNA vaccines
As a natural genetic engineer of plants, Agrobacterium tumefaciens can deliver T-DNA into different eukaryotes, including plant, yeast, fungal and human cells. This DNA transfer represents the only known example of inter-kingdom transfer of genetic information.
We adopt a molecular genetic approach to identify both bacterial and eukaryotic genes responsible for the transfer process. With a combination of molecular genetics, biochemistry and proteomics approaches, we determine the biochemical functions of the novel proteins encoded by the genes involved in the process. These will help illustrate the transfer process.
The T-DNA is delivered by the bacterium into eukaryotic cells in the form of nucleoprotein complex. We are in a unique and effective position to illustrate the T-DNA complex trafficking pathway inside the eukaryotic cells before the DNA integration occurs. We use the Agrobacterium-eukaryote DNA delivery system as a model system to study the fundamental process of nucleoprotein trafficking, which might be relevant to some of the issues in human gene therapy and HIV viral infection.
Based on our knowledge on the transfer process, we will design and develop novel Agrobacterium-based DNA delivery systems for gene therapy. In addition, we will develop novel gene and protein delivery systems for various organisms.
Lopez-Goni, I., Manterola, L and Pan, S. Q. (2004) The Brucella BvrS/BvrR two-component regulatory system: common regulatory strategies of plant and animal pathogens. In Molecular and Cellular Biology of Brucella. I. Lopez-Goni and I. Moriyón, eds. Horizon Scientific Press. Chapter 10. 432 pp.
Yang H., J. Yu, S. Ramachandran, and S.Q. Pan (2003) Rice Genomics Vol. 1: A holistic approach to rice research and genetic engineering. World Scientific Publishing Co.
Li, L., J. H. Jia, Q. M. Hou, T. C. Charles, E. W. Nester and S. Q. Pan (2002) A global pH sensor: Agrobacterium sensor protein ChvG regulates acid-inducible genes on its two chromosome s and Ti plasmid. Proceedings of National Academy of Sciences USA. 99: 12369-12374.
Li, L. Y. H. Jia and S. Q. Pan (2002) Agrobacterium flagellar switch gene fliG is liquid inducible and important for virulence. Canadian Journal of Microbiology. 48: 753-758 .
Jia Y. H., L. P. Li, Q. M. Hou and S. Q. Pan (2002) An Agrobacterium gene involved in tumorigenesis encodes an outer membrane protein exposed on the bacterial cell surface Gene 284: 113-124.
Xu, X. Q., L. P. Li and S. Q. Pan (2001) Feedback regulation of an Agrobacterium catalase gene katA involved in Agrobacterium-plant interaction. Molecular Microbiology 42: 645-657.
Xu, X. Q. and S. Q. Pan (2000) Agrobacterium catalase is a virulence factor involved in tumorigenesis. Molecular Microbiology 35: 407-414.
Pan, S. Q., S. Jin, M. I. Boulton, M. Hawes, M. P. Gordon and E. W. Nester (1995) An Agrobacterium virulence factor encoded by a Ti plasmid gene or a chromosomal gene is required for T-DNA transfer into plants. Molecular Microbiology 17: 259-269.
Jin, S., Y. Song, S. Q. Pan and E. W. Nester (1993) Characterization of a virG mutation that confers constitutive virulence gene expression in Agrobacterium. Molecular Microbiology7: 555-565.
Pan, S. Q., T. Charles, S. Jin, Z. Wu and E. W. Nester (1993) Preformed dimeric state of the sensor protein VirA is involved in plant-Agrobacterium signal transduction. Proceedings of National Academy of Sciences USA . 90: 9939-9943.