People Detail

Faculty Biography For:

George Fox
Ph.D., Syracuse University, 1974

Biology and Biochemistry Department
University of Houston
Houston, Texas 77204-5001

Office: HSC 424
Phone: (713) 743-8363
Curriculum Vitae  

Key Words;Molecular Evolution, Bioinformatics, RNA structure and Evolution, Origin of Life, Environmental Monitoring, Molecular Biology, Array Hybridization, 
The Fox laboratory engages in a combination of basic and associate applied research. Much of our work focuses on RNA including studies of structure and evolution. The applied work relates primarily to applications of RNA technology in space flight and environmental monitoring. Our laboratory combines theoretical and experimental work. We commonly use the modern tools of microbiology, molecular biology and bioinformatics and high-speed computation.

A unifying theme behind the basic research projects in our laboratory is to understand the early evolution of life. To this end we are especially interested in the structure, function and evolution of RNA. Considerable evidence suggests that an RNA World preceded the modern protein world. It is our belief that this RNA World was terminated by the development of an RNA catalyzed mechanism for peptide synthesis. It is presumably this mechanism that was the basis for the modern ribosome. Comparative genomics studies done by others and us suggest that an essentially modern ribosome already existed by the time the current earliest detectable common ancestor of all extant life had developed. Thus, the ribosome presumably developed during the final transition from the prebiotic RNA World to true organisms. By deciphering the origins of the ribosome we can obtain a window into that earliest period in lifeís history. The key to our approach is to identify many instances in which one can argue that one component is older or newer than another. Currently, we are using an intensive bioinformatics approach to identify such events. For example, we have been able to identify what are likely the oldest regions of the RNA by examining the interconnectivity between regions- older regions having been around longer have had more time to develop interconnectivity. We are using both high- resolution structural data and genomics data in these studies.

In order to better understand the RNA World we need to better understand the evolutionary potential of RNA. In our view, there are many primary sequences that are consistent with any particular functional RNA. These sequences are a subset of the total RNA sequence space that can be referred to as a shape space or structure space. If one knew all the sequences that belong to a shape space one couldstochastically predict local evolutionary rates, transitions to other shape spaces and many other evolutionary properties. In order to study RNA shape space, we are using 5S rRNA as a model system. Our immediate objective is to develop algorithms that predict which sequences do or do not belong to a local region of 5S rRNA shape space. We expect to accomplish this by using three kinds of data, all of which are potentially obtainable for any RNA. These are; sequences of valid sequences from extant organisms, three-dimensional structures of one or more examples, and the in vivo phenotypic effect of single point changes at every position in the RNA. The laboratory phase of the project has two phases. First we are using site directed mutagenesis to obtain the required point mutation data. Second, we have developed an in vivo assay system that will allow us to examine the phenotype of the many random multiple event mutations needed to test and validate our predictions.

A key requirement in understanding the evolution of RNA and the composition of RNA shape spaces is to be able to predict the structure of RNAs from primary sequence data alone. In order to make progress on this RNA folding problem, we have categorized all the non-standard base-base interactions that have been encountered in RNA structure determinations. In doing so we recently discovered a new RNA folding motif and are currently seeking to develop rules needed to design new algorithms for RNA structure prediction. We also collaborate with Dr. Xiaolian Gao of the Chemistry Department to examine the structure of interesting small RNAs by high resolution NMR.

The genomics aspect of our work has led to a collaboration with Dr. William Widger of our department and Dr. Janet Siefert at Rice University in which we are seeking to better understand the evolutionary history of the cyanobacteria. Cyanobacteria played a key role in the early Earthís ecosystem and are thought to have been responsible for the rise in oxygen. We have identified cyanobacterial signature genes, most of which have no known function. In the future, we will be using hybridization array technology to examine the expression patterns of these genes in order to obtain insight to their roles. We also are continuing our comparative studies of cyanobacterial genomes.

Several applied research projects stem directly from this basic research on RNA. One of these relates to stable artificial RNAs derived from 5S rRNA. The idea here came from our discovery that it is possible to remove a section of the 5S rRNA and replace it with most any sequence less than 100 nucleotides in length without drastically changing the stability of the RNA product. The resulting artificial RNA accumulates in cells in very large amounts just as if it were a ribosomal RNA. However, it does not enter the ribosome. Moreover, the presence of the artificial RNA has no substantial effect on growth rate beyond that due to the wasteful synthesis. We are exploring the possibility of developing artificial RNAs that chelate metals or encode metal binding peptides that would chelate metals. In either case the host bacterium would obtain metal resistance that would facilitates its use in bioremediation. Another application of artificial RNAs that we are actively pursuing is in environmental monitoring.

Ribosomal RNA is in general an excellent tool for determining the genetic affinity of microorganisms. In collaboration with Dr. Richard Willson of the Chemical Engineering Department we are using RNA sequence information to develop methodology to detect and monitor bacteria and possibly viruses in space environments. This work includes the development of rapid methods of obtaining DNA and RNA samples for analysis as well as state of the art methods such as array hybridization to implement assays.

Highlander SK, Hultén KG, Qin X, Jiang H, Yerrapragada S, Mason EO Jr, Shang Y, Williams TM, Fortunov RM, Liu Y, Igboeli O, Petrosino J, Tirumalai M, Uzman A, Fox GE, Cardenas AM, Muzny DM, Hemphill L, Ding Y, Dugan S, Blyth PR, Buhay CJ, Dinh HH, Hawes AC, Holder M, Kovar CL, Lee SL, Liu W, Nazareth LV, Wang Q, Zhou J, Kaplan SL, Weinstock GM. (2007). Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus. BMC Microbiology, 7:99.

Zhu D, Fox GE, Chakravarty S. (2007). RECOVIR: an application package to automatically identify some single stranded RNA viruses using capsid protein residues that uniquely distinguish among these viruses. BMC Bioinformatics, 8:379.

Gioia J, Yerrapragada S, Qin X, Jiang H, Igboeli OC, Muzny D, Dugan-Rocha S, Ding Y, Hawes A, Liu W, Perez L, Kovar C, Dinh H, Lee S, Nazareth L, Blyth P, Holder M, Buhay C, Tirumalai MR, Liu Y, Dasgupta I, Bokhetache L, Fujita M, Karouia F, Eswara Moorthy P, Siefert J, Uzman A, Buzumbo P, Verma A, Zwiya H, McWilliams BD, Olowu A, Clinkenbeard KD, Newcombe D, Golebiewski L, Petrosino JF, Nicholson WL, Fox GE, Venkateswaran K, Highlander SK, Weinstock GM. (2007). Paradoxical DNA Repair and Peroxide Resistance Gene Conservation in Bacillus pumilus SAFR-032. PLoS ONE, 2(9):e928.

Karpathy SE, Qin X, Gioia J, Jiang H, Liu Y, Petrosino JF, Yerrapragada S, Fox GE, Haake SK, Weinstock GM, Highlander SK. (2007). Genome sequence of Fusobacterium nucleatum subspecies polymorphum - a genetically tractable fusobacterium. PLoS ONE, 2(7):e659.

Warmflash D, Larios-Sanz M, Jones J, Fox GE, McKay DS. (2007)Biohazard potential of putative Martian organisms during missions to Mars. Aviation, Space, and Environmental Medicine, 78(4 Suppl):A79-88.

Stepanov VG, Fox GE. (2007). Stress-driven in vivo selection of a functional mini-gene from a randomized DNA library expressing combinatorial peptides in Escherichia coli. Molecular Biology and Evolution, 24(7):1480-91.

Viswanath L, Lu Y, Fox GE. (2007). Genome display tool: visualizing features in complex data sets. Source Code for Biology and Medicine, 2:1.

Gioia J, Qin X, Jiang H, Clinkenbeard K, Lo R, Liu Y, Fox GE, Yerrapragada S, McLeod MP, McNeill TZ, Hemphill L, Sodergren E, Wang Q, Muzny DM, Homsi FJ, Weinstock GM, Highlander SK. (2006). The genome sequence of Mannheimia haemolytica A1: insights into virulence, natural competence, and Pasteurellaceae phylogeny. Journal of Bacteriology,188(20):7257-66.

Petrosino JF, Xiang Q, Karpathy SE, Jiang H, Yerrapragada S, Liu Y, Gioia J, Hemphill L, Gonzalez A, Raghavan TM, Uzman A, Fox GE, Highlander S, Reichard M, Morton RJ, Clinkenbeard KD, Weinstock GM. (2006). Chromosome rearrangement and diversification of Francisella tularensis revealed by the type B(OSU18) genome sequence. Journal of Bacteriology, 188(19):6977-85.

Hury J, Nagaswamy U, Larios-Sanz M, Fox GE. (2006). Ribosome origins: the relative age of 23S rRNA Domains. Origins Of Life And Evolution Of The Biosphere : The Journal Of The International Society For The Study Of The Origin Of Life, 36(4):421-9.

Putonti C, Luo Y, Katili C, Chumakov S, Fox GE, Graur D, Fofanov Y. (2006). A computational tool for the genomic identification of regions of unusual compositional properties and its utilization in the detection of horizontally transferred sequences. Molecular Biology and Evolution, 23(10):1863-8.

Cano T, Murphy JC, Fox GE, & Willson RC, Separation of Genomic DNA from Plasmid DNA by selective renaturation with IMAC capture, Biotechnol. Prog. 21: 1472-1477 (2005).

Tucker DL, Karouia F, Wang J, Luo Y, Li, TB, Willson RC, Fofanov Y,

Zhao Q., Nagaswamy U, Lee H, Xia Y, Huang HC, Gao,X & Fox, GE. NMR Structure and Mg2 Binding of an RNA Segment that Underlies the L7/L12 Stalk in the E. coli 50S Ribosomal Subunit, Nucleic Acids Res. 33: 3145-3153 (2005).

Huang HC, Nagaswamy U, Fox GE.The application of cluster analysis in the intercomparison of loop structures in RNA. RNA. 2005 Apr;11(4):412-23.

Nagaswamy U, Larios-Sanz M, Zhang Z, Huang H-C, & Fox GE. "Non- Canonical Interactions in RNA." in Recent Developments in Nucleic Acids, Transworld Research Network, 1: 103-129 (2004).

McLeod MP, Karpathy SE, Gioia J, Qin X, Highlander SK, Fox GE, et al., & Weinstock GM. "The Complete Genome of Rickettsia typhi and Comparison with R. prowazekii and R. conorii", J. Bacteriol. 186: 5842-5855 (2004).

Forsman ZH, Lednickey JA, Fox GE, Willson RC, White Z, Halvorson S, Wong C, Lewis AM, & Butel JS. "Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation." J. Virology 78: 9306-9316 (2004)

Fox GE & Naik AK, "The Evolutionary History of the Ribosome" in The Genetic Code and the Origin of Life (L. Ribas de Poplana and P. Schimmel, eds), Landes Bioscience, Chapter 6, pp 92-105 (2004).

Huang, H-C., Nagaswamy, U., and Fox, G. E. "Detection and Classification of RNA Motifs", Submitted to RNA (October 2004).

Larios-Sanz M, Kourentzi KD, Murphy JC, Maillard KI, Pearson DL, Willson RC, & Fox GE. "Estudio de las Poblaciones Microbiologicas en el Ambiente Espacial." in: Dianostico Molecular JGH Editors SA de CV, Mexico City, Mexico, pp 293-311 (2003).

Murphy JC, Fox GE, & Willson RC, "Enhancement of Anion-Exchange Chromatography of DNA Using Compaction Agents." J. Chromatogr. A 984: 215-221 (2003).

D'Souza LM, Larios-Sanz M, Setterquist RA, Willson RC, & Fox GE. "Small RNA sequences are readily stabilized by inclusion in a carrier rRNA." Biotechno. Progr. 19: 734-738 (2003).

Murphy JC, Jewell DL, White KI, Fox GE, & Willson RC. "Nucleic Acid Separations Using Immobilized Metal Affinity Chromatography." Biotechnol. Progr. 19: 982-986 (2003).

DeWalt B, Murphy JC, Fox GE, & Willson, RC. "Compaction Agent Clarification of Microbial Lysates." Protein Exp. Purif. 28: 220-223(2003).

Martin KA, Siefert JL, Yerrapragada Y, Lu Y, McNeil TZ, Moreno PA, Weinstock GM, Widger WR, & Fox GE. "Cyanobacterial Signature Genes." Photosynthesis Research, 75: 211-221 (2003).

Nagaswamy U & Fox GE. "RNA Ligation and the Origin of tRNA." Origins Life & Evol. Biosphere, 33:199-209 (2003).

Kourentzi KD, Fox GE, & Willson RC. "Hybridization-responsive Fluorescent DNA Probes Containing the Adenine Analog 2-AminoPurine." Analytical Biochemistry, 322: 124-126 (2003).

Balan S, Murphy JC, Galaev I, Kumar A, Fox GE, Mattiasson B & Willson RC "Metal Chelate Affinity Precipitation of RNA and Purification of Plasmid DNA." Biotechnol. Lett., 25:1111-1116 (2003).

Martin KA, Siefert JL, Yerrapragada S, Lu Y, McNeill TZ, Moreno PA, Weinstock GM, Widger WR, Fox GE.(2003). Cyanobacterial signature genes. Photosynthesis Research, 75(3):211-21.

Zhang Z, D'Souza LM, Lee YH, Fox GE. (2003). Common 5S rRNA variants are likely to be accepted in many sequence contexts. Journal of Molecular Evolution, 56(1):69-76.

Nagaswamy U, Larios-Sanz M, Hury J, Collins S, Zhang Z, Zhao Q, & Fox GE. "NCIR: A Database of Non-Canonical Interactions in Known RNA Structures." Nucl. Acids Res. 29: 395-397 (2002)

Zhang Z, Willson RC, & Fox GE. "Identification of Characteristic Oligonucleotides in the 16S Ribosomal RNA Sequence Dataset." Bioinformatics, 18: 244-250 (2002).

Nagaswamy U & Fox GE. "Frequent Occurrence of the T-loop RNA Folding Motif in Ribosomal RNAs." RNA, 8: 1112-1119 (2002).

Starikov D, Boney C, Medelci N, Um J-W, Larios-Sanz M, Fox GE., & Bensaoula An. "Experimental Simulation of Integrated Optoelectronic Sensors Based on III Nitrides." J. Vacuum Science & Technology B, 20: 1815-1820 (2002). Starikov, D., Boney

Larkin DC, Williams AM, Martinis SA, Fox GE. (2002). Identification of essential domains for Escherichia coli tRNA(leu) aminoacylation and amino acid editing using minimalist RNA molecules. Nucleic Acids Research, 30(10):2103-13.

Fox GE, Magrum LJ, Balch WE, Wolfe RS, Woese CR. (1977). Classification of methanogenic bacteria by 16S ribosomal RNA characterization. Proceedings Of The National Academy Of Sciences Of The United States Of America, 74(10):4537-4541.