Robert Haselkorn

We study the molecular genetics of nitrogen fixation and cellular differentiation in cyanobacteria as well as genes encoding the enzyme acetyl-CoA carboxylase (ACC) in plants, in apicomplexan parasites and in humans. The cyanobacterium Anabaena grows in filaments of 100 cells or more. When starved for nitrogen, specialized cells called heterocysts differentiate from the photosynthetic vegetative cells at regular intervals along each filament. Heterocysts are anaerobic factories for nitrogen fixation; in them, the nitrogenase enzyme complex is synthesized and the oxygen-evolving photosystem II is turned off. More than 1000 genes are differentially expressed during the irreversible development of heterocysts from vegetative cells. We have sequenced genes for nitrogen fixation, for components of the photosynthetic apparatus and for the sigma and core subunits of RNA polymerase. Among mutants unable to fix nitrogen aerobically are some with altered heterocyst pattern or morphology. We have used complementation to isolate the genes defective in many of these mutants. They encode proteins that participate in environment-sensing regulatory cascades. The relationships among these regulatory proteins are being studied using the Green Fluorescent Protein as a cell-specific reporter of gene expression. Fatty acid synthesis begins in all organisms with the reaction catalyzed by ACC. In chicken, rat, yeast and plants all of the ACC domains reside in a single polypeptide. Yeast cells expressing wheat ACC are sensitive to herbicides that target the enzyme. Yeast expressing chimeras of the cytoplasmic and chloroplast form of the wheat ACC permit determination of the amino acid residues responsible for herbicide binding. We also have yeast strains expressing active ACC from Toxoplasma gondii, suitable for screening for new inhibitors of the parasite. Current experiments have constructed yeast strains expressing active human ACC, which serve in screens for new drugs for obesity.

We study the molecular genetics of nitrogen fixation and cellular differentiation in cyanobacteria as well as genes encoding the enzyme acetyl-CoA carboxylase (ACC) in plants, in apicomplexan parasites and in humans. The cyanobacterium Anabaena grows in filaments of 100 cells or more. When starved for nitrogen, specialized cells called heterocysts differentiate from the photosynthetic vegetative cells at regular intervals along each filament. Heterocysts are anaerobic factories for nitrogen fixation; in them, the nitrogenase enzyme complex is synthesized and the oxygen-evolving photosystem II is turned off. More than 1000 genes are differentially expressed during the irreversible development of heterocysts from vegetative cells. We have sequenced genes for nitrogen fixation, for components of the photosynthetic apparatus and for the sigma and core subunits of RNA polymerase. Among mutants unable to fix nitrogen aerobically are some with altered heterocyst pattern or morphology. We have used complementation to isolate the genes defective in many of these mutants. They encode proteins that participate in environment-sensing regulatory cascades. The relationships among these regulatory proteins are being studied using the Green Fluorescent Protein as a cell-specific reporter of gene expression. Fatty acid synthesis begins in all organisms...

Haselkorn, R. Cell-cell communication in filamentous cyanobacteria. Molecular Microbiol. 70: 783-785 (2008).  

Haselkorn, R. Heterocyst differentiation and nitrogen fixation in cyanobacteria. In Associative and endophytic nitrogen-fixing bacteria and cyanobacterial associations, C. Elmerich and W. E. Newton, eds. Springer, Dordrecht, Netherlands. pp 233-255 (2007). 

Liu, W., Harrison, D.K., Chalupska, D., Gornicki, P., O’Donnell, C.C., Adkins, S.W., Haselkorn, R. and Williams, R.R. Single-site mutations in the carboxyltransferase domain of plastid acetyl-CoA carboxylase confer resistance to grass-specific herbicides. Proc. Natl Acad Sci. USA 104, 3627-3632 (2007).  

Mulkidjanian AY, Koonin EV, Makarova KS, Mekhedov SL, Sorokin A, Wolf YI, Dufresne A, Partensky F, Burd H, Kaznadzey D, Haselkorn R, Galperin MY. The cyanobacterial genome core and the origin of photosynthesis. Proc Natl Acad Sci U S A. 103: 13126-31 (2006).  

Zuther, E., Huang, S., Jelenska, J., Eilenberg, H., Arnold, E. M., Su, X., Sirikhachornkit, A., Podkowinski, J., Zilberstein, A., Haselkorn, R. and Gornicki, P. (2004). "Complex nested promoters control tissue-specific expression of acetyl-CoA carboxylase genes in wheat." Proc Natl Acad Sci U S A 101: 1403-8.   PubMed Citation

Rouhiainen, L., Vakkilainen, T., Siemer, B. L., Buikema, W., Haselkorn, R. and Sivonen, K. (2004). "Genes coding for hepatotoxic heptapeptides (microcystins) in the cyanobacterium Anabaena strain 90." Appl Environ Microbiol 70: 686-92.   PubMed Citation

Podkowinski, J., Jelenska, J., Sirikhachornkit, A., Zuther, E., Haselkorn, R. and Gornicki, P. (2003). "Expression of cytosolic and plastid acetyl-coenzyme A carboxylase genes in young wheat plants." Plant Physiol 131: 763-72.   PubMed Citation

Kapatral, V., Anderson, I., Ivanova, N., Reznik, G., Los, T., Lykidis, A., Bhattacharyya, A., Bartman, A., Gardner, W., Grechkin, G., Zhu, L., Vasieva, O., Chu, L., Kogan, Y., Chaga, O., Goltsman, E., Bernal, A., Larsen, N., D'Souza, M., Walunas, T., Pusch, G., Haselkorn, R., Fonstein, M., Kyrpides, N. and Overbeek, R. (2002). "Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586." J Bacteriol 184: 2005-18.   PubMed Citation

Ivanova, N., Sorokin, A., Anderson, I., Galleron, N., Candelon, B., Kapatral, V., Bhattacharyya, A., Reznik, G., Mikhailova, N., Lapidus, A., Chu, L., Mazur, M., Goltsman, E., Larsen, N., D'Souza, M., Walunas, T., Grechkin, Y., Pusch, G., Haselkorn, R., Fonstein, M., Ehrlich, S. D., Overbeek, R. and Kyrpides, N. (2003). "Genome sequence of Bacillus cereus and comparative analysis with Bacillus anthracis." Nature 423: 87-91.   PubMed Citation

Jones, K. M., Buikema, W. J. and Haselkorn, R. (2003). "Heterocyst-specific expression of patB, a gene required for nitrogen fixation in Anabaena sp. strain PCC 7120." J Bacteriol 185: 2306-14.   PubMed Citation

Kapatral, V., Ivanova, N., Anderson, I., Reznik, G., Bhattacharyya, A., Gardner, W. L., Mikhailova, N., Lapidus, A., Larsen, N., D'Souza, M., Walunas, T., Haselkorn, R., Overbeek, R. and Kyrpides, N. (2003). "Genome analysis of F. nucleatum sub spp vincentii and its comparison with the genome of F. nucleatum ATCC 25586." Genome Res 13: 1180-9.   PubMed Citation

Luke, K., Radek, A., Liu, X., Campbell, J., Uzan, M., Haselkorn, R. and Kogan, Y. (2002). "Microarray analysis of gene expression during bacteriophage T4 infection." Virology 299: 182-91.   PubMed Citation

Haselkorn, R. Cell-cell communication in filamentous cyanobacteria. Molecular Microbiol. 70: 783-785 (2008).  

Haselkorn, R. Heterocyst differentiation and nitrogen fixation in cyanobacteria. In Associative and endophytic nitrogen-fixing bacteria and cyanobacterial associations, C. Elmerich and W. E. Newton, eds. Springer, Dordrecht, Netherlands. pp 233-255 (2007). 

Liu, W., Harrison, D.K., Chalupska, D., Gornicki, P., O’Donnell, C.C., Adkins, S.W., Haselkorn, R. and Williams, R.R. Single-site mutations in the carboxyltransferase domain of plastid acetyl-CoA carboxylase confer resistance to grass-specific herbicides. Proc. Natl Acad Sci. USA 104, 3627-3632 (2007).  

Mulkidjanian AY, Koonin EV, Makarova KS, Mekhedov SL, Sorokin A, Wolf YI, Dufresne A, Partensky F, Burd H, Kaznadzey D, Haselkorn R, Galperin MY. The cyanobacterial genome core and the origin of photosynthesis. Proc Natl Acad Sci U S A. 103: 13126-31 (2006).  

Zuther, E., Huang, S., Jelenska, J., Eilenberg, H., Arnold, E. M., Su, X., Sirikhachornkit, A., Podkowinski, J., Zilberstein, A., Haselkorn, R. and Gornicki, P. (2004). "Complex nested promoters control tissue-specific expression of acetyl-CoA carboxylase genes in wheat." Proc Natl Acad Sci U S A 101: 1403-8.   PubMed Citation