Areas of Research

Dr. Celeste Brown has two research areas, how gene regulation changes in response to selection, and the evolution of disordered proteins. The link between these two disparate areas is that often proteins involved in gene regulation are disordered. The gene regulation studies involve laboratory-based research and the disordered protein studies involve bioinformatics approaches.

How does gene regulation of bacteriophage phiX change in response to selection? Studies of adaptive evolution of the bacteriophage phiX174 consistently show changes in the phage’s genome that do not affect its protein sequences. Our research centers on discovering whether these adaptive changes are affecting the timing or levels of gene transcription, with the eventual goal of also studying mRNA stability and the timing and levels of translation.

Do disordered proteins evolve differently than ordered proteins? Disordered proteins are proteins or parts of proteins that do not fold into fixed 3-dimensional structures the way ordered proteins do. Recent interest in disordered protein has led to overwhelming evidence of its functional importance in many biological  systems. Our previous research showed that there are important differences between ordered and disordered protein in the rate at which they evolve and in the way that they evolve. We are attempting to define the evolutionary forces that are causing these differences.

Publications

DeGelder, Leen, Frederick P. J. Vandecasteele, Celeste J. Brown, Larry J. Forney and Eva M. Top, Plasmid donor affects host range of the promiscuous IncP-1b plasmid pB10 in an activated sludge microbial community. Applied and Environmental Microbiology (in press).

Oldfield, Christopher J., Yugong Cheng, Mark S. Cortese, Celeste J. Brown, Vladimir N. Uversky and A. Keith Dunker. 2005. Comparing and combining predictors of mostly disordered proteins. Biochemistry 44:1989-2000.

Peng, Kang, Slobodan Vucetic, Predrag Radivojac, Celeste J. Brown, A. Keith Dunker. 2005. Optimizing long intrinsic disorder predictors with protein evolutionary information. Journal of Bioinformatics and Computational Biology 3:35-60.

Vucetic, Slobodan, Zoran Obradovic, Vladimir Vacic, Predrage Radivojac, Kang Peng, Lilia M. Iakoucheva, Marc S. Cortese, J. David Lawson, Celeste J. Brown, Jason G. Sikes, Crystal D. Newton and A. Keith Dunker. 2004. DisProt: a database of protein disorder. Bioinformatics 21:137-140.

Iakoucheva, Lilia M., Predrag Radivojac, Celeste J. Brown, Timothy R. O’Connor, Jason G. Sikes, Zoran Obradovic, and A. Keith Dunker. 2004. The importance of intrinsic disorder for protein phosphorylation. Nucleic Acids Research 32: 1037-1049.

Radivojac, Predrag, Zoran Obradovic, David K. Smith, G. Zhu, Slobodan Vucetic, Celeste J. Brown, J. David Lawson, and A. Keith Dunker. 2004. Protein flexibility and intrinsic disorder. Protein Science 13: 71-80.

Obradovic, Zoran, Peng Kang, Slobodan Vucetic, Predrag Radivojac, Celeste J. Brown, and A. Keith Dunker. 2003. Predicting intrinsic disorder from amino acid sequence. PROTEINS: Structure, Function, Genetics 53: 566-572.

Vucetic, Slobodan, Celeste J. Brown, A. Keith Dunker, and Zoran Obradovic. 2003. Flavors of protein disorder. PROTEINS: Structure, Function, Genetics 52: 573-584.

Radivojac, Predrag, Zoran Obradovic, Celeste J. Brown and A. Keith Dunker.  2003.  Prediction of boundaries between intrinsically ordered and disordered protein regions.  Pacific Symposium on Biocomputing, 8: 216-227.

Iakoucheva, Lilia M., Celeste J. Brown, J. David Lawson, Zoran Obradovic and A. Keith Dunker. 2002. Intrinsic disorder in cell-signaling and cancer-associated proteins. Journal of Molecular Biology 323: 573-584.

Brown, Celeste J., Sachiko Takayama, Andrew M. Campen, Pamela Vise, Thomas Marshall, Christopher J. Oldfield, Christopher J. Williams, A. Keith Dunker.  2002. Evolutionary rate heterogeneity in proteins with long disordered regions. Journal of Molecular Evolution 55: 102-107.

Radivojac, Predrag, Zoran Obradovic, Celeste J. Brown, and A. Keith Dunker. 2002. Improving sequence alignments for intrinsically disordered proteins. Pacific Symposium on Biocomputing 7: 589-600.

Bailey, Robert W., A. Keith Dunker, Celeste J. Brown, Ethan C. Garner, and Michael D. Griswold.  2001. Clusterin, a binding protein with a molten globule-like region.  Biochemistry, 40: 11828-11840.

Vucetic, S., P. Radivojac, C. J. Brown, A. K. Dunker and Z. Obradovic. 2001. Methods for improving protein disorder prediction, Proceedings of the International Joint INNS-IEEE Conference on Neural Networks. 4: 2718-2723.

Brown, Celeste J., Ethan C. Garner, A. Keith Dunker and Paul Joyce. 2001. The power to detect recombination using the coalescent.  Molecular Biology Evolution 18: 1421-1424.

Iakoucheva, Lilia M., Amy L. Kimzey, Christophe D. Masselson, James E. Bruce, Ethan C. Garner, Celeste J. Brown, A. Keith Dunker, Richard D. Smith, and Eric J. Ackerman.  2001.  Identification of intrinsic order and disorder in the DNA repair protein XPA.  Protein Science 10: 560-571. 

Dunker, A. K., J. D.Lawson, C. J. Brown, R. M. Williams, P. Romero, J. Oh, C. J. Oldfield, A. M. Campen, C. M. Ratliff, K. W. Hipps. J. Ausio, M. S. Nissen, R. Reeves, C. -H.  Kang, C. R. Kissinger, R. W.  Bailey, M. D. Griswold, W. Chiu, E. C. Garner, and Z. Obradovic. 2001.  Intrinsically disordered protein,  Journal of  Molecular Graphics and Modelling, 19: 26-59.

Williams, R. M., Z. Obradovic, V. Mathura, W. Braun, E. C. Garner, J. Young, S. Takayama, C. J. Brown, and A. K. Dunker. 2001.  The protein non-folding problem: amino acid determinants of intrinsic order and disorder. Pacific Symposium on Biocomputing 6: 89-100.

Romero, Pedro, Zoran Obradovic, Xiaohong Li, Ethan C. Garner, Celeste J. Brown, and A. Keith Dunker. 2001. Sequence complexity of disordered protein,  PROTEINS: Structure, Function, Genetics  42: 38-48.

Dunker, A. Keith, Zoran Obradovic, Pedro Romero, Ethan C. Garner, and Celeste J. Brown. 2000.  Intrinsic protein disorder in complete genomes.  Genome Informatics 11: 161-171.

Li, Xiaohong, Zoran Obradovic, Celeste J. Brown, Ethan C. Garner, and A. Keith Dunker. 2000. Comparing predictors of disordered protein.  Genome Informatics 11: 172-184.

Garner, Ethan, Pedro Romero, A. Keith Dunker, Celeste Brown, and Zoran Obradovic. 1999. Predicting binding regions within disordered proteins.  Genome Informatics 10: 41-50.

Brown, Celeste J., Kristy M. Todd, and R. Frank Rosenzweig.  1998. Multiple duplications of a yeast hexose transport gene in response to selection in a glucose-limited environment. Molecular Biology Evolution 15: 931-942.

Edenberg, Howard J., Celeste J. Brown, Man-Wook Hur, Shailaja Kotagiri, Mei Li, Lu Zhang and Xin Zhi.  1996.  Regulation of the seven human alcohol dehydrogenase genes. Enzymology and Molecular Biology of Carbonyl Metabolism 6. Plenum Press, N.Y. pp. 339-345.

Brown, Celeste J., Lu Zhang, and Howard J. Edenberg.  1996. Gene expression in a young multigene family: Tissue-specific differences in the expression of the human alcohol dehydrogenase genes ADH1, ADH2 and ADH3.  DNA and Cell Biol. 15: 187-196.

 Edenberg, Howard J., Celeste J. Brown, and Lu Zhang. 1995. Alcohol dehydrogenases: molecular biology and gene regulation. Alcohol. Alcohol. Suppl. 2: 121-125.

Brown, Celeste J., Lu Zhang, and Howard J. Edenberg. 1994. Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter. DNA and Cell Biol. 13: 235-247.

Edenberg, Howard J., Celeste J. Brown and Lu Zhang. 1993. Regulation of the human alcohol dehydrogenase genes ADH1, ADH2 and ADH3: Differences in cis-acting sequences at CTF/NF-I sites. Advances in Experimental Medical Biology  328: 561-570.

Hur, Man-Wook, Wei-Hsien Ho, Celeste J. Brown, David Goldman, and Howard J. Edenberg. 1992. Molecular cloning of mouse alcohol dehydrogenase-B₂ cDNA: nucleotide sequences of the class III ADH genes evolve slowly. DNA Sequence 3: 167-175.

Edenberg, Howard J. and Celeste J. Brown. 1992. Regulation of human alcohol dehydrogenase genes. Pharmacogenetics 2: 185-196.

Brown, Celeste J., Kathryn A. Baltz and Howard J. Edenberg. 1992. Expression of the ADH2 gene: An unusual Sp1 site in the promoter of a liver-enriched gene. Gene 121: 313-320.

Anderson, W. W., J. Arnold, D. G. Baldwin, A. T. Beckenbach, C. J. Brown, S. H. Bryant, J. A. Coyne, L. G. Harshman, W. B. Heed, D. E. Jeffrey, L. B. Klaczko, B. C. Moore, J. A. Moore, J. M. Porter, J. R. Powell, T. Prout, S. W. Schaeffer, J. C. Stephens, C. E. Taylor, M. E. Turner and G. O. Williams. 1991. Four decades of inversion polymorphism in Drosophila pseudoobscura. Proceedings of the National Academy of S cience (USA)  88: 10367-10371.

Edenberg, H.J., C. J. Brown, L. G. Carr, W. H. Ho and M. W. Hur. 1990. Alcohol dehydrogenase gene expression, and cloning of the mouse c-like ADH. H. Weiner (ed.), Proceedings of the Fifth International Workshop on Enzymology and Molecular Biology of Carbonyl Metabolism. Plenum Press, N.Y.

Hawley, Sylvia A., Rodney A. Norman, Celeste J. Brown, Winifred W. Doane, Wyatt W. Anderson and Donal Hickey. 1990. Somatic transformation of Drosophila melanogaster by amylase genes from Drosophila pseudoobscura, Drosophila miranda and an Oregon-R strain of D. melanogaster. Genome 33: 501-508.

Brown, Celeste J., Charles F. Aquadro and Wyatt W. Anderson. 1990. DNA sequence evolution of the amylase multigene family in Drosophila pseudoobscura. Genetics 126: 131-138.

Williams, Christopher J., Wyatt W. Anderson, Celeste J. Brown and Jonathan Arnold. 1989. An analysis of density-dependent viability selection. Journal of the American Statistical Association 84: 662-668.

Brown, Celeste J., Wyatt W. Anderson, William D. Burbanck and Courtney T. Hackney. 1988. Genetic transition between northern and southern populations of the estuarine isopod, Cyathura polita, and the discovery of a new species of Cyathura. Estuaries. 11: 96-98.

Brown, Celeste J., Virginia G. Dunbar and David A. Shafer. 1986. A comparison of the karyotypes of six species of the genus Macaca and a species of the genus Cercocebus. Folia Primatologica 46: 164-172.

Seager, R. D., W. W. Anderson and C. J. Brown. 1985. Apparent neutrality of amylase in Drosophila pseudoobscura grown on starch and maltose media. Drosophila Information Service 61: 147.

Anderon, Wyatt W. and Celeste J. Brown. 1984. A test for rare male mating advantage with Drosophila pseudoobscura karyotypes. Genetics 107: 577-589.

Anderson, Wyatt W., C. Wayne Berisford, Robert H. Turnbow and Celeste J. Brown. 1983. Genetic differences among populations of the black turpentine beetle, Dendroctonus tenebrans, and an engraver beetle, Ips calligraphus (Coleoptera: Scolytidae). Annals of the Entomological Society of America 26: 896-902.

Brown, Celeste J. and I.Lehr Brisbin. 1983. Genetic analysis of pariah cat populations from the southeastern United States. Journal of Heredity 74: 344-348.

Invited Reviews

Forney, Larry J., Xia Zhou and Celeste J. Brown, 2004. Molecular microbial ecology: land of the one-eyed king. Current Opinion in Microbiology 7:210-220.

 Dunker, A. Keith, Celeste J. Brown, J. David Lawson, Lilia M. Iakoucheva, and Zoran Obradovic. 2002. Intrinsic  disorder and protein function. Biochemistry 41: 6573-6582.

Dunker, A. Keith, Celeste J. Brown and Zoran Obradovic, 2002. Identification and functions of usefully disordered proteins. Advances in Protein Chemistry 62: 25-49.