Dennis W. Grogan

Ph.D.: University of Illinois, Urbana-Champaign 1985

MICRO-ORGANISMS FROM EXTREME ENVIRONMENTS
MOLECULAR BIOLOGY OF HYPERTHERMOPHILES
GENETICS OF ARCHAEA

Much of the biochemical diversity of life on earth is embodied in single-celled organisms.  The smallest and most widely distributed of these consist of extremely small "prokaryotic" cells that lack nuclei or other membranous organelles.  The best-known prokaryotes, bacteria, include a few species that cause disease, but the vast majority of bacteria mediate geochemical cycling, degrade toxic pollutants, or produce antibiotics or other useful products. 

Over 35 years ago, Carl Woese discovered a second, evolutionarily distinct, group of prokaryotes through analysis of ribosomal RNA sequences.  Much less is known about this second lineage, called Archaea. Many of the archaea that have been successfully grown in pure culture come from hostile or otherwise unusual environments, yet they show certain similarities to eukaryotic cells at the molecular level.

The Grogan lab focuses on thermoacidophilic archaea of the genus Sulfolobus. These species normally live in acidic hot springs, and their optimal growth conditions (80º C and pH 3) quickly inactivate the DNA, RNA, enzymes, and membranes found in "ordinary" cells.  We seek to understand in molecular terms how the Sulfolobus cell functions under these harsh conditions.  Sulfolobus cells are known to have intrinsically thermostable enzymes and a cell-envelope architecture found only in archaea. It is less clear how they maintain the integrity of their genomes under geothermal conditions, however, as several protein families associated with DNA repair in eukaryotes, bacteria, and even mesophilic archaea are missing from Sulfolobus species and other hyperthermophilic archaea.

To address this challenge, research in the Grogan lab emphasizes experimental techniques that analyze genetic processes in vivo.  We have isolated various mutant strains of Sulfolobus acidocaldarius and used them to investigate archaeal cell division, responses to DNA damage, transfer and recombination of chromosomal DNA, and the fidelity of genome replication (see Publications list).  Current interests focus on functional properties of homologous recombination, DNA repair, and trans-lesion DNA synthesis.

Grant: #1 F33 GM088933-01 Investigators:Dennis Grogan 10-2009 -10-2010 National Institute of General Medical Sciences Role of cross-link formation in Pol Zeta-dependent mutagenesis in S. cerevisiae Role:Trainee $59000 Completed Type:Fellowship Level:National

Grant: #1 R15 GM097704-01 Investigators:Dennis Grogan 2011 -2014 NIH Homologous recombination in hyperthermophilic archaea Role:Principle Investigator 300000 Denied Type:Grant Level:National

Grant: #MCB 0543910 Investigators:Grogan, Dennis 03-01-2006 -02-28-2011 National Science Foundation Functional Assessment of Mismatch Repair and Nucleotide Excision Repair in Sulfolobus Species Role:PI $369,999.00 Completed Type:Grant Level:National

Grant: #MCB-9733303-NSF-NCE Investigators:Grogan, Dennis 06-15-1998 -05-31-2005 National Science Foundation Enhancing Education through Research Experiences, and Investigations of Gene Functions in Archaea Role:PI $469,585.00 Closed Level:Federal

Grant: #Faculty Research Grant Investigators:Dennis Grogan 01-2011 -12-2011 University Research Council Genetic Assays for Molecular Interactions in Sulfolobus Spp. Role:P.I. 6300 Completed Type:Grant Level:University

Investigators:Raven Huang, P.I.; D. Grogan, W. Whitman, B. Wilson, J. Cronan co-PIs 2013 -2018 National Institutes of Health Structure and Function of the Elongator complex Role:Co-PI 50000 + indirect Denied Type:Grant

Grant: #MCB1330493 Investigators:D. Grogan 08-2013 -07-2016 National Science Foundation Processes and genes controlling mutation in the Sulfolobus genome Role:P.I. 490008 Denied Type:Grant

Grant: #1R01GM107533-01A1 Investigators:R.Huang (PI); W. Whitman, B. Wilson, D. Grogan 04-2014 -03-2019 National Institutes of Health Structure and Function of the Elongator Complex Role:Co-PI UC subaward: $50000 + indirect Pending Type:Grant

Grant: #1412046 Investigators:D. Grogan 07-2014 -06-2017 National Science Foundation Mechanisms of hyperthermophilic archaea that cope with unrepaired DNA damage Role:P.I. 483941 Pending Type:Grant

Grant: #2013-01835-02 / R01 GM107533 Investigators:Grogan, Dennis 09-30-2014 -07-31-2016 National Institute of General Medical Sciences Structure and Function of the Elongator Complex Role:PI $37,000.00 Active Level:Federal

Grant: #R25078 Investigators:Grogan, Dennis 04-01-2019 -03-31-2020 UC's URC Faculty Research Cost Support Awards Program DNA Stabilization Technology for Hyperthermophiles Role:PI $7,300.00 Active Level:Internal UC

Peer Reviewed Publications

Mao D, Grogan DW. 2017. How a genetically stable extremophile evolves: Modes of genome diversification in the archaeon Sulfolobus acidocaldarius. J. Bacteriol. 199:e00177-17

Grogan DW. 2015. Understanding DNA repair in hyperthermophilic archaea: Persistent gaps and other reasons to focus on the fork. 2015. Archaea 2015:942605.

Sakofsky CJ, Grogan DW. Lesion-induced mutation in the hyperthermophilic archaeon Sulfolobus acidocaldarius and its avoidance by the Y-Family DNA polymerase Dbh. Genetics. 2015 Oct;201(2):513-23.

Hauber DJ, Grogan DW, DeBry RW. Mutations to less-preferred synonymous codons in a highly expressed gene of Escherichia coli: Fitness and epistatic interactions. PLoS One. 2016 Jan 4;11(1):e0146375.

Sakofsky CJ, Grogan DW. 2013. Endogenous mutagenesis in recombinant Sulfolobus plasmids. J Bacteriol. 195: 2776-2785

Kissling,G, Grogan DW, Drake JW. 2013. Confounders of mutation-rate estimators: selection and phenotypic lag in Thermus thermophilus.  Mutat. Res. 749:16-20

Rockwood, J, Mao, D, Grogan DW. 2013. Homologous recombination in the archaeon Sulfolobus acidocaldarius: effects of DNA substrates and mechanistic implications. Microbiology 159: 1888-1899

Grogan, DW, Jinks-Robertson S. 2012. Formaldehyde-induced mutagenesis in Saccharomyces cerevisiae: molecular properties and the roles of repair and bypass systems.  Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Sakofsky CJ, Foster PL, Grogan DW. 2012. Roles of the Y-family DNA polymerase Dbh in accurate replication of the Sulfolobus genome at high temperature.  DNA Repair (Amst).11:391-400

Mao, DM and Grogan, DW. 2012. Genomic evidence of rapid, global-scale gene flow in a Sulfolobus species. Internat. Soc. Microb. Ecol. J. 6: 1613-1616

Mao D, Grogan DW. 2012. Heteroduplex formation, mismatch resolution, and genetic sectoring during homologous recombination in the hyperthermophilic archaeon Sulfolobus acidocaldarius. Frontiers Microbiol. 3: 192

Sakofsky CJ, Runck LA, Grogan, DW. 2011. Sulfolobus mutants, generated via PCR products, which lack putative enzymes of UV photoproduct repair. Archaea 2011:864015

Ajon M, Fröls S, van Wolferen M, Stoecker K, Teichmann D, Driessen AJ, Grogan DW, Albers SV, Schleper C. 2011. UV-inducible DNA exchange in hyperthermophilic archaea mediated by type-IV pili. Mol Microbiol. 82:807-17

Grogan, D.W., Rockwood J. 2010. Discontinuity and limited linkage in the homologous recombination system of a hyperthermophilic archaeon. Journal of Bacteriology 192: 4660-4668

Grogan D.W. 2009.  Homologous recombination in Sulfolobus acidocaldarius: genetic assays and functional properties. Biochemical Society Transactions. 37:88-91

Mackwan, R.R., Carver, G.T., Kissling, G.E., Drake, J.W., Grogan, D.W. 2008. The rate and character of spontaneous mutation in Thermus thermophilus. Genetics 180: 17-25.

Grogan, D.W., Ozarzak, M.A., & Bernander, R. (2008). Variation in gene content among geographically diverse Sulfolobus isolates. Environ. Microbiol., 10, 137-146.

Grogan, Dennis W., Stengel, Kristy R. (2008). Recombination of synthetic oligonucleotides with prokaryotic chromosomes: substrate requirements of the Escherichia coli. Molecular microbiology, 69(5), 1255, 1265.

Mackwan, Reena R., Carver, Geraldine T., Drake, John W., Grogan, Dennis W. (2007). An unusual pattern of spontaneous mutations recovered in the halophilic archaeon Haloferax volcanii. Genetics, 176(1), 697, 702.

Berkner, S., Grogan, D.W., Albers, S.V., & Lipps, G. (2007). Small multicopy, non-integrative shuttle vectors based on the plasmid pRN1 for Sulfolobus acidocaldarius and Sulfolobus solfataricus, model organisms of the (cren-)archaea. Nucleic Acids Research, 35.

Blount, Z.D., & Grogan, D.W. (2005). New Insertion Sequences of Sulfolobus: Functional properties and implications for genome evolution in hyperthermophilic archaea. Molecular Microbiology, 55, 312-325.

Hansen, J.E., Dill, A.C., & Grogan, D.W. (2005). Conjugational genetic exchange in the hyperthermophilic archaeon Sulfolobus acidocaldarius: Intragenic recombination with minimal dependence on marker separation. Journal of Bacteriology, 187, 805-809.

Whitaker, R.J., Grogan, D.W., & Taylor, J.W. (2005). Recombination shapes the natural population structure of the hyperthermophilic archaeon Sulfolobus islandicus. Molecular Biology and Evolution, 22(12), 2354-2361.

Kurosawa, N., & Grogan, D.W. (2005). Homologous recombination of exogenous DNA with the Sulfolobus acidocaldarius genome: Properties and uses. FEMS Microbiology Letters, 253(1), 141-149.

Grogan, D.W. (2004). Stability and repair of DNA in hyperthermophilic archaea. Current Issues in Molecular Biology, 6, 137-144.

Whitaker, R.J., Grogan, D.W., & Taylor, J.W. (2003). Geographic barriers isolate endemic populations of hyperthermophilic archaea. Science, 301, 976-978.

Grogan, D. W., Hansen, J. E. (2003). Molecular characteristics of spontaneous deletions in the hyperthermophilic archaeon Sulfolobus acidocaldarius. Journal of Bacteriology, 185(4), 1266, 1272.

Grogan, D. W. (2003). Cytosine methylation by the SuaI restriction-modification system: Implications for genetic fidelity in a hyperthermophilic archaeon. Journal of Bacteriology, 185(15), 4657, 4661.

Reilly, M. S., Grogan, D. W. (2002). Biological effects of DNA damage in the hyperthermophilic archaeon Sulfolobus acidocaldarius. FEMS microbiology letters, 208(1), 29, 34.

Grogan, D. W., Carver, G. T., Drake, J. W. (2001). Genetic fidelity under harsh conditions: Analysis of spontaneous mutation in the thermoacidophilic archaeon Sulfolobus acidocaldarius. Proceedings of the National Academy of Sciences of the United States of America, 98(14), 7928, 7933.

Reilly, M. S., Grogan, D. W. (2001). Characterization of intragenic recombination in a hyperthermophilic archaeon via conjugational DNA exchange. Journal of Bacteriology, 183(9), 2943, 2946.

Grogan, D. W. (2000). The question of DNA repair in hyperthermophilic archaea. Trends in microbiology, 8(4), 180, 185.

Bernander, R., Poplawski, A., Grogan, D. W. (2000). Altered patterns of cellular growth, morphology, replication and division in conditional-lethal mutants of the thermophilic archaeon Sulfolobus acidocaldarius. Microbiology-Uk, 146, 749, 757.

Schmidt, K. J., Beck, K. E., Grogan, D. W. (1999). UV stimulation of chromosomal marker exchange in Sulfolobus acidocaldarius: Implications for DNA repair, conjugation and homologous recombination at extremely high temperatures. Genetics, 152(4), 1407, 1415.

Maiorano, J. N., Grogan, D. W. (1999). Extremely thermostable orotidine-5 ';-monophosphate decarboxylase from the archaeon Sulfolobus acidocaldarius. FEMS microbiology letters, 174(1), 81, 87.

Jacobs, K. L., Grogan, D. W. (1998). Spontaneous mutation in a thermoacidophilic archaeon: evaluation of genetic and physiological factors. Archives of Microbiology, 169(1), 81, 83.

Ghane, F., Grogan, D. W. (1998). Chromosomal marker exchange in the thermophilic archaeon Sulfolobus acidocaldarius: physiological and cellular aspects. Microbiology-Uk, 144, 1649, 1657.

Grogan, D. W. (1998). Hyperthermophiles and the problem of DNA instability. Molecular microbiology, 28(6), 1043, 1049.

Grogan, D. W. (1997). Photoreactivation in an archaeon from geothermal environments. Microbiology-Uk, 143, 1071, 1076.

Wood, E. R., Ghane, F., Grogan, D. W. (1997). Genetic responses of the thermophilic archaeon Sulfolobus acidocaldarius to short-wavelength UV light. Journal of Bacteriology, 179(18), 5693, 5698.

Jacobs, K. L., Grogan, D. W. (1997). Rates of spontaneous mutation in an archaeon from geothermal environments. Journal of Bacteriology, 179(10), 3298, 3303.

Grogan, D. W., Cronan, J. E. (1997). Cyclopropane ring formation in membrane lipids of bacteria. Microbiology and Molecular Biology Reviews, 61(4), 429, &.

Grogan, D. W. (1996). Organization and interactions of cell envelope proteins of the extreme thermoacidophile Sulfolobus acidocaldarius. Canadian journal of microbiology, 42(11), 1163, 1171.

Grogan, D. W. (1996). Isolation and fractionation of cell envelope from the extreme thermo-acidophile Sulfolobus acidocaldarius. Journal of microbiological methods, 26(1-2), 35, 43.

Grogan, D. W. (1996). Exchange of genetic markers at extremely high temperatures in the archaeon Sulfolobus acidocaldarius. Journal of Bacteriology, 178(11), 3207, 3211.

Wang, A. Y., Grogan, D. W., Cronan, J. E. (1992). Cyclopropane Fatty-Acid Synthase of Escherichia-Coli - Deduced Amino-Acid-Sequence, Purification, and Studies of the Enzyme Active-Site. Biochemistry, 31(45), 11020, 11028.

Grogan, D. W. (1989). Phenotypic Characterization of the Archaebacterial Genus Sulfolobus - Comparison of 5 Wild-Type Strains. Journal of Bacteriology, 171(12), 6710, 6719.

Grogan, D. W. (1988). Temperature-Sensitive Murein Synthesis in an Escherichia-Coli Pdx Mutant and the Role of Alanine Racemase. Archives of Microbiology, 150(4), 363, 367.

Grogan, D. W. (1986). Auxotrophic Basis for the Envelope-Defective Phenotype of an Escherichia-Coli Mutant. Current microbiology, 14(2), 107, 111.

Grogan, D. W., Cronan, J. E. (1986). Characterization of Escherichia-Coli Mutants Completely Defective in Synthesis of Cyclopropane Fatty-Acids. Journal of Bacteriology, 166(3), 872, 877.

Grogan, D. W., Cronan, J. E. (1984). Cloning and Manipulation of the Escherichia-Coli Cyclopropane Fatty-Acid Synthase Gene - Physiological-Aspects of Enzyme Overproduction. Journal of Bacteriology, 158(1), 286, 295.

Grogan, D. W. (1984). Interaction of Respiration and Luminescence in a Common Marine Bacterium. Archives of Microbiology, 137(2), 159, 162.

Grogan, D. W., Cronan, J. E. (1984). Genetic-Characterization of the Escherichia-Coli Cyclopropane Fatty-Acid (Cfa) Locus and Neighboring Loci. Molecular & General Genetics, 196(2), 367, 372.

Grogan, D. W., Cronan, J. E. (1983). Use of Lambda Phasmids for Deletion Mapping of Non-Selectable Markers Cloned in Plasmids. Gene, 22(1), 75, 83.

Grogan, D. W. (1983). The Response of Bacterial Luminescence to an Inhibitor of Fatty-Acid Biosynthesis. Archives of Microbiology, 136(2), 137, 139.

Book Chapter

Grogan, D.W. (2016) Chapter 18: Proteins of DNA Replication from Extreme Thermophiles: PCR and Beyond.  In P.H. Rampelotto (Ed) Biotechnology of Extremophiles: Advances and challenges. Springer International Publishing, Switzerland.

Grogan, D.W. 2012. Chapter 50: Physiology of Prokaryotic Cells.  In N. Sperelakis (Ed) Cell Physiology Sourcebook, fourth edition: Essentials of Membrane Biophysics. pp. 891-906. Academic Press/Elsevier, London

Grogan D.W. (2006). Archaea - Physiology, Molecular Biology and Evolution. In Garrett, R.A. and Klenk, H.-P. (Eds.), Genetic properties of Sulfolobus acidocaldarius and related archaea Malden, MA: Blackwell Publishing.

Grogan D.W. (2007). Archaea: Molecular and Cellular Biology. In R. Cavicchioli (Eds.), Chapter 5: Mechanisms of genome stability and evolution (pp. 120-138). American Society for Microbiology: Washington, D.C.

White, M.F. & Grogan, D.W. (2008). Thermophiles: Biology and technology at high temperatures. In F.T. Robb et al. (Eds.), Chapter 10: DNA stability and repair (pp. 179-187). Boca Raton FL: CRC Press.

Grogan, D.W. (2008). Thermophiles: Biology and technology at high temperatures. In F.T. Robb et al. (Eds.), Chapter 12: Genetic analysis in extremely thermophilic bacteria: An overview (pp. 205-211). Boca Raton FL: CRC Press.

Editorial

Ettema TJ, Lindås AC, Hjort K, Poplawski AB, Kaessmann H, Grogan DW, Kelman Z, Andersson AF, Pelve EA, Lundgren M, Svärd SG. 2014. Rolf Bernander (1956-2014): pioneer of the archaeal cell cycle. Mol Microbiol. 92:903-9.

Encyclopedia Article

Extreme Thermophiles. In: eLS 2013, John Wiley & Sons Ltd: Chichester http://www.els.net/More Information