Sean M. Callahan

Sean Callahan


Sean received an AB in Molecular Biology from Princeton University in 1988 and, after working for 5 years in industry, returned to science and completed a PhD in Biological Oceanography at MIT and the Woods Hole Oceanographic Institution in 1999. His doctoral work explored the quorum sensing regulon of Vibrio fischeri and its involvement in symbiosis between the bioluminescent bacterium and the Hawaiian bobtail squid Euprymna scolopes. As an NIH postdoctoral fellow he worked with Bob Haselkorn at the University of Chicago on the developmental program of heterocyst differentiation in filamentous cyanobacteria.In 2002 Sean started as an associate professor in the Department of Microbiology at the University of Hawaii at Manoa.

Now a full professor, his lab typically consists of 5 -10 postdocs, graduate and undergraduate students who continue the developmental work on patterning and differentiation of heterocysts in the cyanobacterium Anabaena or work on a second project developed in collaboration with Greta Aeby of the Hawaii Institute for Marine Biology on the roles of bacteria in coral health.
Snyder 201

Courses Taught

  • MICR475 Bacterial Genetics (fall)
  • MICR475L Laboratory in Bacterial Genetics (fall)
  • MICR314 Research Ethics (spring)
  • MICR671 Bacterial Genetics (spring)
  • MICR614 Research Ethics (spring)

Research Interests

  • There are two research projects in our lab. In the first a filamentous cyanobacterium is used to study the molecular genetics of cellular differentiation and the generation of periodic patterns. Using the filamentous cyanbacterium Anabaena as a model, we are studying how a lack of bioavailable nitrogen induces the formation of nitrogen fixing heterocysts, how cells communicate with one another to determine which cells of the organism will differentiate, how cells irreversibly commit to differentiation, and how morphological changes in these cells are orchestrated.
  • The second project looks at the contributions of bacteria, both commensals and pathogens, to the health of corals. This project is a collaboration with Greta Aeby of the Hawaii Institute of Marine Biology. The types of bacteria, their locations in the coral animal and their potential roles in coral health are focuses of current studies. Montipora white syndrome (MWS) is a progressive tissue loss disease found on reefs throughout the Hawaiian archipelago and is particularly prevalent in Kaneohe Bay, Oahu, where Montipora capitata is ubiquitous. We have developed a model coral disease system that is being used to explore many components of the host, pathogen and environment triangle of disease causation.

Current Research

Project 1: Developmental biology of heterocyst differentiation and patterning in a filamentous cyanobacterium

We are investigating the basic mechanisms of pattern generation and maintenance as well as the qualities of a regulatory network that lead to terminal differentiation of cells. We use primarily molecular genetic approaches.

The development of a pattern of differentiated cell types from a group of equivalent cells is a fundamental paradigm in biology. The hallmark of differentiation is the creation of self-sustaining patterns of gene regulation and protein activity.

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Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium that can be induced to differentiate a periodic pattern of nitrogen-fixing heterocysts from a chain of undifferentiated vegetative cells. Heterocysts occur, on average, at 10 cell intervals, are terminally differentiated, and differ from vegetative cells morphologically, metabolically, and genetically.

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They allow the spatial separation of the two incompatible processes of photosynthesis and nitrogen fixation. As an example of division of labor between cells type, heterocysts provide vegetative cells with fixed nitrogen and receive fixed carbon from vegetative cells.

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Patterning of differentiation appears to be dependent on the interactions between several proteins, some of which are indicated above in a schematic of the stages of differentiation. The first, HetR, is part of a regulatory circuit that shares the properties of biological switches, which turn graded input signals into a binary output: when the switch is “off”, the cell remains undifferentiated, but when the switch is “turned on”, the differentiation process begins and eventually becomes irreversible and self-sustaining. HetR acts to promote differentiation and is both necessary and sufficient to induce differentiation. PatS is a protein that prevents differentiation, and is responsible for determining the de novo patterning of heterocysts on a filament. HetN produces a signal involved in stabilization and maintenance of the pattern once it has formed.

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The relative positions of cells is conveyed by concentration gradients of PatS and/or HetN extending from source cells. PatS and HetN prevent the activity of HetR and cause its decay as can be seen in the micrograph above where fluorescence from HetR-GFP is reduced next to heterocysts, which are sources of HetN and PatS. The phenomenon of “lateral inhibition” of differentiation has been proposed to govern patterning in many developmental systems.

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Lateral inhibition in Anabaena is most easily conceptualized when considering the placement of a new heterocyst between two existing heterocysts after the vegetative cells between them have divided.

Project 2 - Roles of bacteria in coral health

Coral reefs are essential for healthy oceans. They act as nurseries for juvenile fish, turtles, and crustaceans; they protect coastlines; and they provide food for millions of people. Unfortunately, the health of coral reefs worldwide is under threat by disease. In collaboration with Greta Aeby of the Hawaii Institute of Marine Biology (HIMB), we are investigating the ecology and epidemiology of coral diseases and the roles of microbes in coral health.

Healthy coral harbor a specific set of bacteria that is conserved among similar coral. Unfortunately, bacteria are also the cause of several diseases that affect corals. We are currently focusing on two diseases found in Hawaii, Montipora White Syndrome and Black Band Disease.

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Montipora White Syndrome

Montipora white syndrome (MWS) is a progressive tissue loss disease found on reefs throughout the Hawaiian archipelago and is particularly prevalent in Kaneohe Bay, Oahu, where the Hawaiian rice coral Montipora capitata is ubiquitous.

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Montipora white syndrome (MWS) is a progressive tissue loss disease found on reefs throughout the Hawaiian archipelago and is particularly prevalent in Kaneohe Bay, Oahu, where the Hawaiian rice coral Montipora capitata is ubiquitous.
In MWS, the white skeleton is exposed after coral tissue is lysed. Skeleton exposed earlier is colonized by algae that appear light green.

Early work identified the bacteria Vibrio owensii and Vibrio coralliilyticus in diseased coral. They were subsequently shown to recreate disease in laboratory infections. Currently we are searching for sources of these pathogens, environmental factors that facilitate disease, physiological pathways such as quorum sensing associated with disease, and virulence genes that contribute to infection. We are characterizing the bacterial communities associated with healthy and diseased M. capitata, investigating the role of resident microflora in preventing disease, and testing methods of treatment.

Black Band Disease

We are currently investigating the first recorded outbreak of Black Band Disease (BBD) in the Hawaiian Islands. As for BBD found in other parts of the world, BBD in Hawaii appears to be a poly-microbial disease that includes a filamentous cyanobacterium, Beggiatoa, and sulfur-reducing bacteria. Research focuses on environmental drivers of the disease that allow these three types of bacteria, which are commonly found in marine sediments, to establish an infection on coral.

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BBD presents as a black band separating healthy coral (orange tissue in lower right) from exposed coral skeleton (recently exposed white skeleton and older algae-covered skeleton above black band).

Coral probiotics

Bacteria that reside on healthy coral are believed to contribute to the coral's defenses against pathogens. Recently we have been testing this hypothesis directly and have found that certain strains of bacteria act as "probiotics"; when added to coral they prevent the subsequent infection by known pathogens. Whether these bacteria directly inhibit the growth of a pathogen, modify the structure of the bacterial community to one that excludes a pathogen or work by some other mechanism is an open question that we hope to answer.

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Selected Publications

  1. Videau, P, Rivers OS, Higa KC, Callahan SM (2015) ABC transporter required for intercellular transfer of developmental signals in a heterocystous cyanobacterium. J. Bacteriol. 197:2685-2693.
  2. Aeby GS, Work TM, Runyon CM, Shore-Maggio A, Ushijima B, Videau P, Callahan SM. (2015) First Record of Black Band Disease in the Hawaiian Archipelago: Response, Outbreak Status, Virulence, and Method of Treatment. PloS ONE doi:10.1371/journal.pone.0120853.
  3. Beurmann S, Videau P, Ushijima B, Smith AM, Aeby GS, Callahan SM, Belcaid M. (2015) Complete Genome Sequence of Pseudoalteromonas sp. Strain OCN003, Isolated from Kāneʻohe Bay, Oʻahu, Hawaiʻi. Genome Announc. 3:e01396–14.
  4. Ushijima B, Videau P, Poscablo D, Vine V, Salcedo M, Aeby G, Callahan SM. (2014) Complete Genome Sequence of Vibrio coralliilyticus Strain OCN014, Isolated from a Diseased Coral at Palmyra Atoll. Genome Announc. 2:e01318–14–e01318–14.
  5. Videau, P., Cozy, L. M., Young, J. E., Ushijima, B., Oshiro, R. T., Rivers, O. S., Burger, A. H., and Callahan, S. M. (2015) The trpE gene negatively regulates differentiation of heterocysts at the level of induction in Anabaena sp. strain PCC 7120. J. Bacteriol. 197:362-370.
  6. Rivers, O. S., Videau, P., and Callahan, S. M. (2014) Mutation of sepJ reduces the intercellular signal range of a hetN-dependent paracrine signal, but not of a patS-dependent signal, in the filamentous cyanobacterium Anabaena sp. strain PCC 7120. Mol. Microbiol. 94:1260-1271
  7. Videau, P., Oshiro, R. T., Cozy, L. M., Callahan, S. M. (2014) Transcriptional dynamics of developmental genes assessed with an FMN-dependent fluorophore in mature heterocsyts of Anabaena sp. strain PCC 7120. Microbiology 160:1874-1881
  8. Ushijima, B., Videau P., Burger, A., Shore-Maggio, A., Runyon, C.M., Sudek, M., Aeby, G.S., Callahan, S.M. (2014) Vibrio coralliilyticus strain OCN008 is an etiological agent of acute Montipora white syndrome. Appl. Environ. Microb. 80(7):2102-2109.
  9. Videau, P., Ni, S., Rivers, O. S., Ushijima, B., Feldman, E. A., Cozy, L. M., Kennedy, M. A., Callahan, S. M. (2014) Expanding the direct HetR regulon in Anabaena sp. strain PCC 7120. J. Bacteriol. 196:1113-1121.
  10. Williams, G. J., Price, N. N., Ushijima, B., Aeby, G. S., Callahan, S., Davy, S. K., Gove, J. M., Johnson, M. D., Knapp, I. S., Shore-Maggio, A., Smith, J. E., Videau, P., Work, T. M. (2014) Ocean warming and acidification have complex interactive effects on the dynamics of a marine fungal disease. Proc. R. Soc. B. 281:20133069 doi:10.1098/rsb2013.3069
  11. Ushijima, B., Videau,, P., Aeby, G.S., Callahan, S.M. (2013) Draft Genome Sequence of Vibrio coralliilyticus strain OCN008 Isolated from Kāne‘ohe Bay, Hawai‘i. Genome Announc. September/October 2013 1:e00786-13; doi:10.1128/genomeA.00786-13.
  12. Kim, Y., Yeb, Z., Joachimiak, G., Videau, P., Young, J., Hurd, K. Callahan, S. M., Gornicki, P., Zhao J., Haselkorn, R., Joachimiak, A. (2013) Structures of complexes comprised of Fischerella transcription factor HetR with Anabaena DNA targets. Proc. Natl. Acad. Sci. 110(19):E1716-1723.
  13. Ushijima B, Smith A, Aeby GS, Callahan SM (2012) Vibrio owensii Induces the Tissue Loss Disease Montipora White Syndrome in the Hawaiian Reef Coral Montipora capitata. PLoS ONE 7: e46717. doi:10.1371/journal.pone.0046717.
  14. Huang, Y., Callahan, S. M. and Hadfield, M. G. (2012) Recruitment in the sea: bacterial genes required for inducing larval settlement in a polychaete worm. Sci. Rep. 2, doi:10.1038/srep00228.
  15. Higa, K. C., Rajagopalan, R., Risser, D. D., Rivers, O. S., Tom, S. K., Videau, P. and Callahan, S. M. (2012) The RGSGR amino acid motif of the intercellular signaling protein, HetN, is required for patterning of heterocysts in Anabaena sp. strain PCC 7120. Mol. Microbiol. 83:682-693.
  16. Tom, S. K. and S. M. Callahan. (2012) The putative phosphatase all1758 is necessary for normal growth, cell size, and synthesis of the minor heterocyst-specific glycolipid in the cyanobacterium Anabaena sp. strain PCC 7120. Microbiology. 158:380-389.
  17. Feldman, E. A., Ni, S., Sahu, I. D., Mishler, C. H., Levengood, J. D., Kushnir, Y., McCarrick, R. M., Lorigan, G. A., Tolbert, B. S., Callahan, S. M., and Kennedy, M. A. (2012) Differential binding between PatS C-terminal peptide fragments and HetR from Anabaena sp. PCC 7120. Biochemistry 51:2436-2442.
  18. Kim, Y., Joachimiak, G., Zi, Y., Binkowski, T. A., Zhang, R., Gornicki, P., Callahan, S. M., Hess, W. R., Haselkorn, R. & Joachimiak, A. (2011) Structure of the transcription factor HetR required for heterocyst differentiation in cyanobacteria. Proc. Natl. Acad. Sci. 108: 10109-10114.
  19. Feldman, E. A., Ni, S., Sahu, I. D., Mishler, C. H., Risser, D. D., Murakami, J. L., Tom, S. K., McCarrick, R. M., Lorigan, G. A., Tolbert, B. S., Callahan, S. M. & Kennedy, M. A. (2011) Evidence for direct binding between HetR from Anabaena sp. PCC 7120 and PatS-5. Biochemistry 50: 9212-9224.
  20. Higa, K. C. & Callahan, S. M. (2010) Ectopic expression of hetP can partially bypass the need for hetR in heterocyst differentiation by Anabaena sp. strain PCC 7120. Mol. Microbiol. 77: 562-574.
  21. Young-Robbins, S. S., D. D. Risser, J. Moran, R. Haselkorn and S. M. Callahan. (2010) Transcriptional regulation of the heterocyst patterning gene patA from Anabaena sp. strain PCC 7120. J. Bacteriol. 192:4732-4740.
  22. Zhu, M., S. M. Callahan and J. A. Allen. (2010) Maintenance of heterocyst patterning in a filamentous cyanobacterium. J. Biol. Dyn. 4:621-633.
  23. Rajagopalan, R. and S. M. Callahan. (2010) Temporal and spatial regulation of the four transcription start sites of hetR from Anabaena sp. strain PCC 7120. J. Bacteriol. 192:1088-1096
  24. Risser, D. D. and S. M. Callahan. (2009) Genetic and cytological evidence that heterocyst patterning is regulated by inhibitor gradients that promote activator decay. Proc. Nat. Acad. Sci., USA 106:19884-19888.
  25. Risser, D. D. and S. M. Callahan. 2008. HetF and PatA control levels of HetR in Anabaena sp. strain PCC 7120. J. Bacteriol. 190:7645-7654.
  26. Qin, N., Callahan, S. M., Dunlap, P. V., and A. M. Stevens. (2007) Analysis of LuxR Regulon Gene Expression during Quorum Sensing in Vibrio fischeri MJ-100. J. Bacteriol. 189:4127-4134.
  27. Risser, D. D. and S. M. Callahan. (2007) Mutagenesis of hetR reveals amino acids necessary for HetR function. J. Bacteriol. 189:2460-2467
  28. Nayar A. S., H. Yamaura, R. Rajagopalan, D. D. Risser and S. M. Callahan. (2007) FraG is necessary for filament integrity and heterocyst maturation in the cyanobacterium Anabaena sp. strain PCC 7120. Microbiology. 153: 601-607.
  29. Orozco, C. C., Risser, D. D., and S. M. Callahan. (2006) Epistasis analysis of four genes from Anabaena sp. Strain PCC 7120 suggests a connection between PatA and PatS in heterocyst pattern formation. J. Bacteriol. 188:1808-1816.
  30. Borthakur, P. B., Orozco, C. C., Young-Robbins, S. S., Haselkorn, R., and S. M. Callahan. (2005) Inactivation of patS and hetN causes lethal levels of heterocyst differentiation in the filamentous cyanobacterium Anabaena sp. PCC 7120. Mol. Microbiol. 57:111-123.

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