Faculty & Research
- Contact Information
- Contact David Kehoe by dkehoe [at] indiana [dot] edu
- By telephone: 812-856-4715
- JH A413A
- Research Areas
- Genomics and Bioinformatics
- Microbial Cell Biology and Environmental Responses
- Plant Molecular Biology
Ph.D., University of California, Los Angeles, 1992
NSF Postdoctoral Fellow, Carnegie Institution, Stanford University, 1993
Indiana University Outstanding Junior Faculty Award, 2003
Indiana University Trustees’ Teaching Award, 2002, 2006, 2007, 2012
Indiana University Senior Class Award for Teaching Excellence in Biology and Dedication to Undergraduates, 2007
Howard Hughes Medical Institute/National Academy of Sciences Summer Institute Fellow, 2010
American Academy of Microbiology Fellow, 2015
My research group is broadly interested in uncovering the molecular mechanisms that control how organisms sense and respond to changes in their environment. Our primarily focus is on the cyanobacteria, oxygen producing microorganisms that are the progenitors of land plants and responsible for nearly one half of the Earth’s current primary productivity. This group is excellent for our studies because they have successfully colonized nearly every type of habitat on Earth (and thus are capable of a wide range of responses to environmental change), have small genome sizes, grow rapidly, and many molecular genetic tools are available for their study. Our research efforts are providing important new insights into signal transduction pathways that are found in both bacteria and plants.
Cyanobacteria respond to a wide range of abiotic cues, including changes in light color and intensity, nutrient availability, temperature, and pH. We are currently focused on uncovering the signaling systems that control cellular responses to changes in light color and nutrient (especially sulfur and nitrogen) availability. As we discover how these sensory pathways operate, we are working towards the long-term goal of understanding how signals from multiple environmental stimuli are integrated into a final, coherent cellular response. Our research tools include molecular biological, biochemical, genetic, and comparative and functional genomic approaches. Our projects on light color and nutrient responses are explained in more detail below.
Regulating Responses to Changing Light Color
Virtually all photosynthetic organisms on our planet acclimate to changes in ambient light color. The colorful process of complementary chromatic adaptation (CCA) is the best studied example of such acclimation (Figure 1). CCA is a reversible response that occurs in many freshwater and marine cyanobacterial species. The most dramatic phenotype of CCA is a reversible change in cell color from brick red during growth in green light to bright blue green during growth in red light. Although this color change appears simple, our functional genomics research has shown that this spectacular event involves complex cellular responses. The most dramatic of these is the modification of the light harvesting antennae used for photosynthesis (Figure 2). In red light, the antennae contain large amounts of a chromophore-containing protein called inducible phycocyanin (PC2) that is blue in color and efficiently absorbs red light. In green light, the antennae contain a chromophore-containing protein called phycoerythrin, which most effectively absorbs green light and is red colored. These changes appear to help cyanobacteria efficiently utilize both red-enriched light (when they are present near the water surface) and green-enriched light (when they reside deeper in the water column).
Our research is revealing the complexity of the signal transduction that regulates CCA. Multiple light regulated pathways control the transcription of the genes encoding antennae apoproteins and the corresponding chromophore biosynthetic enzymes. One of these consists of a red-green light photoreceptor called RcaE, the first discovered member of a group of bacterial photoreceptors with similarity to a class of plant photoreceptors called phytochromes. RcaE controls a complex two-component signal transduction pathway that contains two response regulators, RcaF and RcaC. A second, newly discovered pathway is called the Cgi system and only controls the responses of green-light activated genes. We are using biochemical approaches to understand the Rca pathway’s mechanism of action and genetic approaches to uncover the components of the Cgi signaling pathway that we recently identified.
Regulating Responses to Nutrient (Sulfur) Deprivation
Cyanobacteria provide themselves with reduced carbon via photosynthesis, and their growth rate in the natural environment is usually restricted due to the availability of various nutrients. Some cyanobacteria have an intriguing response to sulfur deprivation (to which they may be subjected periodically). Depletion of sulfur during red light growth leads to the cessation of PC2 synthesis due to the disappearance of its mRNA. PC2-containing antennae are degraded and replaced by antennae that contain another type of phycocyanin called PC3, whose mRNA accumulates under low sulfur conditions. Why does the cell undergo this process, which can be reversed by subsequently adding sulfur? Amino acid sequence comparisons have shown that PC3 contains far fewer of the sulfur-containing amino acids methionine and cysteine than does PC2. Since PC proteins make up close to 30% of the cellular total, replacing PC2 with PC3 seems to make a large number of sulfur atoms available for further growth. At the same time, cells producing PC3 will utilize the available sulfur more efficiently. The general ability to selectively produce proteins that are depleted or enriched in specific elements in response to the availability of those elements may be widespread among bacteria in nature.
Our laboratory has recently initiated studies examining this sulfur limitation response. We are working towards three goals on this project. First, we are examining the mechanisms that mediate the changes in abundance of the mRNAs encoding PC2 and PC3 after shifts in sulfur levels. Our preliminary data suggest that both transcriptional and posttranscriptional control mechanisms are involved, possibly including antisense RNA regulation. Our second goal is to uncover the regulatory pathways controlling the response using genetic approaches. Our third goal is to determine the degree to which this phenotypic plasticity in sulfur utilization confers a selective advantage to organism that are capable of this response.
- Sanfilippo, J. E., Nguyen, A. A., Karty, J. A., Shukla, A., Schluchter, W. A., Garczarek, L., Partensky, F. and D. M. Kehoe. 2016. A self-regulating genomic island encoding tandem regulators confers chromatic acclimation to marine Synechococcus. Submitted.
- Wiltbank, L. B. and D. M. Kehoe. 2016. Two cyanobacterial photoreceptors regulate photosynthetic light harvesting by sensing teal, green, yellow and red light. mBio. In press.
- Nesbit, A. D., Whippo, C., Hangarter, R. P., and D. M. Kehoe. 2015. Translation initiation factor 3 families: What are their roles in regulating cyanobacterial and chloroplast Gene expression? Photosynth. Res. 126:147-159.
- Yerrapragada, S., Shukla, A., Hallsworth-Pepin, K., Choi, K., Wollam, A., Clifton, S., Qin, X., Muzny, D., Raghuraman, S., Ashki, H., Uzman, A., Highlander, S., Fryszczyn, B., Bingwa, B., Horton-Schaffer, C., Fox, G., Tirumalai, M., Liu, Y., Kim, S., Kehoe, D. M. and G. Weinstock. 2015. Extreme sensory complexity encoded in the 10-Mb draft genome sequence of the chromatically acclimating cyanobacterium Tolypothrix sp. PCC 7601. Genome Announcements, 3 (3).
- Agarwal, R., Hasan, S. S., Jones, L. M., Stofleth, J. T., Ryan, C. M., Whitelegge, J. P., Kehoe, D. M., and W. A. Cramer. 2015. Role of domain-swapping in the hetero-oligomeric cytochrome b6f lipo-protein complex. Biochem. 54: 3151-3163.
Bussell, A. N. and D. M. Kehoe. 2013. Chromatic acclimation: A many-colored mechanism for maximizing photosynthetic light harvesting efficiency. In The Cell Biology of Cyanobacteria. (Ed. E. Flores and A. Herrero) (Caister Academic Press, Norfolk, UK). In press.
- Bussell, A. N. and D. M. Kehoe. 2013. Hierarchical regulation between four-color and two-color cyanobacteriochromes. Proceedings of the National Academy of Sciences USA, 110: 12834-12839.
- Gutu, A., Nesbit, A. D., Alverson, A., Palmer, J. D., and D. M. Kehoe. 2013. Light color regulation of photosynthetic genes by translation initiation factor IF3. Proceedings of the National Academy of Sciences USA, 110: 16253-16258.
- Gutu, A. and D. M. Kehoe. 2012. Emerging perspectives on the mechanisms, regulation, and distribution of light color acclimation in cyanobacteria. Molecular Plant, 5: 1-13.
Shukla, A., Biswas, A., Blot, N., Partensky, F., Karty, J. A., Hammad, L. A., Garczarek, L., Gutu, A., Schluchter, W., and D. M. Kehoe. 2012. A phycoerythrin-specific bilin lyase-isomerase controls blue-green chromatic acclimation in marine Synechococcus. Proceedings of the National Academy of Sciences USA, 109: 20136-20141.
- Bezy, R. P., Wiltbank, L., and D. M. Kehoe. 2011. Light-dependent attenuation of phycoerythrin gene expression reveals convergent evolution of green light sensing in cyanobacteria. Proceedings of the National Academy of Sciences U.S.A., 108: 18542-18547.
- Gutu, A., Alvey, R. M., Bashour, S., Zingg, D., and D. M. Kehoe. 2011. Sulfate-driven elemental sparing is regulated at the transcriptional and post-transcriptional levels in a filamentous cyanobacterium. Journal of Bacteriology, 193: 1449-1460.
- Bezy, R. P. and Kehoe, D. M. 2010. Functional characterization of a cyanobacterial OmpR/PhoB class transcription factor binding site controlling light color responses. Journal of Bacteriology, 192: 5923-5933.
- Kehoe, D. M. 2010. Chromatic adaptation and the evolution of light color sensing in cyanobacteria. Proceedings of the National Academy of Sciences U.S.A., 107: 9029-9030.
Kolowrat, C., Partensky, F., Mella-Flores, D., Le Corguillé, G., Boutte, C., Blot, N., Ratin, M., Ferréol, M., Lecomte, X., Gourvil, P., Lennon, J.-F., Kehoe, D.M., and L. Garczarek. 2010. Ultraviolet stress delays chromosome replication in light/dark synchronized cells of the marine cyanobacterium Prochlorococcus marinus PCC9511. BMC Genomics, 10: 204.
- Shui, J., Saunders, E., Needleman, R., Nappi, M., Cooper, J., Kehoe, D. M., and E. Stowe-Evans. 2009. Identification and expression analysis of light-dependent and light-independent protochlorophyllide oxidoreductases in the chromatically adapting cyanobacterium Fremyella diplosiphon Utex 481. Plant and Cell Physiology, 50: 1507-1521.
- Li, L. and D. M. Kehoe. 2008. Abundance changes of the response regulator RcaC require specific aspartate and histidine residues and are necessary for normal light color responsiveness. Journal of Bacteriology, 190: 7241-7250.
- Li, L., Alvey, R. M., Bezy, R. P., and D. M. Kehoe. 2008. Inverse transcriptional activities during complementary chromatic adaptation are controlled by binding of the response regulator RcaC to red and green light responsive promoters. Molecular Microbiology, 68: 286-297.
- Alvey, R. M., Bezy, R. P., Frankenberg-Dinkle, N., and D. M. Kehoe. 2007. A light regulated OmpR-class promoter element coordinates light harvesting protein and chromophore biosynthetic enzyme gene expression. Molecular Microbiology, 64: 319-332.
- Kehoe, D. M. and A. Gutu. 2006. Responding to color: the regulation of complementary chromatic adaptation. Annual Review of Plant Biology, 57: 127-150.
- Li, L. and D. M. Kehoe. 2005. In vivo analysis of the roles of conserved aspartate and histidine residues within a complex response regulator. Molecular Microbiology, 55: 1538-1552.
- Alvey, R. M., Li, L., Balabas, B., Stowe-Evans, E. L., and D. M. Kehoe. 2005. Signal transduction pathways regulating chromatic adaptation. In Light Sensing in Plants (Ed. M. Wada, K. Shimazaki, and M. Iino) (Springer-Verlag Publishers, Tokyo) pp. 299-306.
- Montgomery, B. L., Casey, E. S., Grossman, A. R., and D. M. Kehoe. 2004. AplA: a member of a new class of phycobiliproteins lacking a traditional role in photosynthetic light harvesting. Journal of Bacteriology, 186: 7420-7428.
- Stowe-Evans, E. L., Ford, J., and Kehoe, D. M. 2004. Genomic DNA microarray analysis: identification of new genes regulated by light in the cyanobacterium Fremyella diplosiphon. J. Bacteriol. 186: 4338-4349.
- Terauchi, K., Montgomery, B. L., Grossman, A. R., Lagarias, J. C., and D. M. Kehoe. 2004. RcaE is a complementary chromatic adaptation photoreceptor required for green and red light responsiveness. Mol. Microbiol. 51: 567-577.
- Stowe-Evans, E. L., and Kehoe, D. M. 2004. Signal transduction during light-quality acclimation in cyanobacteria: a model system for understanding phytochrome-response pathways in prokaryotes. Photochem. Photobiol. Sci. 3: 495-502.