Research:
In my laboratory we are interested in understanding how bacteria integrate diverse environmental signals and diverse metabolic modules to function at the whole cell level. We rely heavily on genome sequencing, mutant construction and analysis, and transcriptome analysis for our work.
One of our goals is to develop the metabolically versatile phototrophic bacterium Rhodopseudomonas palustris as a biocatalyst for the production of hydrogen, a biofuel. We are working to define the metabolic networks that lead to hydrogen generation The metabolic modules of nitrogen metabolism, photosynthesis, biodegradation and oxygen respiration all contribute to these networks, and we are defining the essential components in each network, how they are regulated, and what the rate limiting steps are in order to be able to effectively predict and maximize hydrogen production by Rhodopseudomonas palustris.
Our second area of interest is in sensory signal transduction, biofilm formation and respiration in the opportunistic pathogen Pseudomonas aeruginosa. The lungs of most cystic fibrosis patients become chronically infected with the bacterium P. aeruginosa and this persistent infection causes severe lung damage. P aeruginosa is damaging to lungs because it - for reasons that are still not completely understood - is able to grow to high population densities and form biofilms in the environment of the lung. We have been studying a signal transduction complex comprised of six proteins that controls biofilm formation by modulating intracellular levels of a secondary intracellular messenger called cyclic di-GMP. Somehow this secondary messenger signals cells to turn on the expression of genes needed for biofilm formation. We want to understand the mechanism of cyclic di-GMP signaling. In other work we are addressing how it is that P. aeruginosa cells present in CF lungs can thrive and grow to high population densities in thick mucous. This mucous is highly depleted in oxygen and P. aeruginosa needs oxygen in order to grow. We are investigating the hypothesis that P.aeruginosa cells can grow at very low oxygen tensions.
Selected Publications:
Schuster, M., A. C. Hawkins, C. S. Harwood and E. P. Greenberg, 2004. The Pseudomonas aeruginosa RpoS regulon and its relationship to quorum sensing. Mol. Microbiol. 51:973-985.
Larimer, F. W., P. Chain, J. Lamerdin, S. Stilwagen Malfatti, L. Do, M. Land, L. Hauser, D. A. Pelletier, J. T. Beatty, A. S. Lang, F. R. Tabita, J. L. Gibson, T. E. Hanson, C. Bobst, J. Torres Y Torres, C. Peres, F. Harrison, J. Gibson and C. S. Harwood. 2004. The genome sequence of the metabolically versatile photosynthetic bacterium Rhodopseudomonas palustris. Nature Biotech. 22: 55-61.
Samanta, S. K and C. S. Harwood. 2005. Use of the Rhodopseudomonas palustris genome to identify a single amino acid that contributes to the activity of a coenzyme A ligase with chlorinated substrates. Mol. Microbiol. 55: 1151-1159.
Hickman, J..W., D. R. Tifrea, and C. S. Harwood. in press. A chemosensory system that regulates biofilm formation through modulation cyclic diguanyate levels. Proc. Natl. Acad. Sci. USA.
Oda, Y. , S. K. Samanta, F. Rey, L. Wu, X.-D. Liu, T.-F. Yan, J. Zhou, and C. S. Harwood. in press. A functional genomic analysis of three nitrogenase isozymes in Rhodopseudomonas palustris. J. Bacteriol.
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