- Dept. Biology and Biochemistry
University of Houston
3455 Cullen Blvd. Suite 342
Houston, TX 77204-5001 - 713-743-8363
George E Fox
University of Houston, Biology and Biochemistry, Faculty Member
Research Interests: Chemistry, Analytical Chemistry, Molecular Biology, RNA, Biology, and 14 moreMedicine, DNA, Humans, RNA isolation, Human Genome, Chemical Precipitation, Genomic DNA, RT PCR, Analytical Biochemistry, Reverse Transcriptase, Biochemistry and cell biology, Nucleic Acid, reverse transcriptase polymerase chain reaction, and Reverse transcription polymerase chain reaction
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Introduction: To understand the extent to which complexity can emerge in an RNA World and how it might be effected by peptides or amino acids, we are pursuing a novel experimental approach based on dynamic combinatorial chemistry... more
Introduction: To understand the extent to which complexity can emerge in an RNA World and how it might be effected by peptides or amino acids, we are pursuing a novel experimental approach based on dynamic combinatorial chemistry (DCC)[1,2]. It is hypothesized that when subject to a persistent equilibrium of ligation and cleavage, RNAs will naturally increase in complexity while gaining resistance to degradation over time. It will be of immense interest to see if this equilibrium or the pathways towards increasing complexity are strongly affected by the presence of amino acids or peptides. To obtain such equilibrium, we are using a two enzyme system. The cleavage enzyme is Benzonase [3], which is the commercial name for an extracellular endonuclease secreted by Serratia marcescens. This enzyme cleaves RNA, including circular forms, to produce products with a 3’ hydroxyl and 5’ phosphate. This is ideal for ligation by T4 RNA ligase [4], which requires these exact ends and utilizes AT...
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Motivation: The phylogenetic structure of the bacterial world has been intensively studied by comparing sequences of 16S ribosomal RNA (16S rRNA). This database of sequences is now widely used to design probes for the detection of... more
Motivation: The phylogenetic structure of the bacterial world has been intensively studied by comparing sequences of 16S ribosomal RNA (16S rRNA). This database of sequences is now widely used to design probes for the detection of specific bacteria or groups of bacteria one at a time. The success of such methods reflects the fact that there are local sequence segments that are highly characteristic of particular organisms or groups of organisms. It is not clear, however, the extent to which such signature sequences exist in the 16S rRNA dataset. A better understanding of the numbers and distribution of highly informative oligonucleotide sequences may facilitate the design of hybridization arrays that can characterize the phylogenetic position of an unknown organism or serve as the basis for the development of novel approaches for use in bacterial identification. Results: A computer-based algorithm that characterizes the extent to which any individual oligonucleotide sequence in 16S ...
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Human space travelers experience a unique environment that affects homeostasis and physio-logic adaptation. One of the important regulatory biology interactions affected by space flight is the alteration of the immune response. As such,... more
Human space travelers experience a unique environment that affects homeostasis and physio-logic adaptation. One of the important regulatory biology interactions affected by space flight is the alteration of the immune response. As such, the impairment of the immune system may lead to higher risk of bacterial and/or viral infection during human space flight missions. Mi-crobiological contaminants have been a source
Research Interests: Chemistry, Immune response, Scanning Electron Microscopy, Gene expression, Environmental Change, and 14 moreExtracellular Matrix, Functional Genomics, Space flight, Escherichia coli, Cellular Network, Shear Stress, Physiological Response, Knowledge base, Immune system, Viral Infection, Virulence factor, Long Term Effect, Antimicrobial agent, and Gene expression pattern
Microorganisms are unavoidable in space environments and their presence has, at times, been a source of problems. Concerns about disease during human space missions are particularly important considering the significant changes the immune... more
Microorganisms are unavoidable in space environments and their presence has, at times, been a source of problems. Concerns about disease during human space missions are particularly important considering the significant changes the immune system incurs during spaceflight and the history of microbial contamination aboard the Mir space station. Additionally, these contaminants may have adverse effects on instrumentation and life-support systems. A sensitive, highly specific system to detect, characterize, and monitor these microbial populations is essential. Herein we describe a monitoring approach that uses 16S rRNA targeted molecular beacons to successfully detect several specific bacterial groupings. This methodology will greatly simplify in-flight monitoring by minimizing sample handling and processing. We also address and provide solutions to target accessibility problems encountered in hybridizations that target 16S rRNA.
Research Interests: Computer Science, Environmental microbiology, Biology, Spaceflight, Medicine, and 12 moreLife Support Systems, Humans, Space flight, United States, Pubmed, Feasibility Studies, Bacteria, Medical Physiology, Public health systems and services research, Aviation and Space History, Spacecraft, and Beacon
ABSTRACT Previous space flight experience has demonstrated that microorganisms are just as ubiquitous in space habitats as they are on Earth. Numerous incidences of biofilm formation within space habitats have been reported; some of which... more
ABSTRACT Previous space flight experience has demonstrated that microorganisms are just as ubiquitous in space habitats as they are on Earth. Numerous incidences of biofilm formation within space habitats have been reported; some of which were identified only after damage to spacecraft structures and irritation to astronaut's skin occurred. As we increase the duration of spaceflight missions, it becomes legitimate to question the long-term effects of microgravity on bacteria. To begin this assessment, Escherichia coli K-12 strain MG1655 was grown for one thousand generations (1000G) under low shear modeled microgravity. Subsequently, growth kinetics and the presence of biofilm were assessed in the 1000G strain as compared to a strain (1G) briefly exposed to LSMMG. Overall, the analysis revealed that (i) there was no obvious difference in growth kinetics between the 1G and 1000G strains, and (ii) although biofilm formation was not seen in the 1G strain it did in fact occur as exposure time increased. The results suggest that long-term exposure to the space environment likely favors biofilm formation in many organisms.
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Research Interests: Microbiology, Biology, Fungi, Biodiversity, Medicine, and 15 moreActinobacteria, Humans, Archaea, Bacteria, Cluster Analysis, Microbiome, International Space Station NASA Space Exploration Spaceflight, Microbiota, Controlled Environment Agriculture, Dust, Firmicutes, Cleanroom, Metagenome, Proteobacteria, and Air Microbiology
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Reliable detection and identification of pathogens in complex biological samples, in the presence of contaminating DNA from a variety of sources, is an important and challenging diagnostic problem for the development of field tests. The... more
Reliable detection and identification of pathogens in complex biological samples, in the presence of contaminating DNA from a variety of sources, is an important and challenging diagnostic problem for the development of field tests. The problem is compounded by the difficulty of finding a single, unique genomic sequence that is present simultaneously in all genomes of a species of closely related pathogens and absent in the genomes of the host or the organisms that contribute to the sample background. Here we describe 'host-blind probe design'- a novel strategy of designing probes based on highly frequent genomic signatures found in the pathogen genomes of interest but absent from the host genome. Upon hybridization, an array of such informative probes will produce a unique pattern that is a genetic fingerprint for each pathogen strain. This multiprobe approach was applied to 83 dengue virus genome sequences, available in public databases, to design and perform in silico microarray experiments. The resulting patterns allow one to unequivocally distinguish the four major serotypes, and within each serotype to identify the most similar strain among those that have been completely sequenced. In an environment where dengue is indigenous, this would allow investigators to determine if a particular isolate belongs to an ongoing outbreak or is a previously circulating version. Using our probe set, the probability that misdiagnosis at the serotype level would occur is approximately 1 : 10(150).
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Research Interests: Chemistry and Antibiotics
The extreme halophile Halococcus morrhuae (ATCC® 17082) contains a 108-nucleotide insertion in its 5S rRNA. Large rRNA expansions in Archaea are rare. This one almost doubles the length of the 5S rRNA. In order to understand how such an... more
The extreme halophile Halococcus morrhuae (ATCC® 17082) contains a 108-nucleotide insertion in its 5S rRNA. Large rRNA expansions in Archaea are rare. This one almost doubles the length of the 5S rRNA. In order to understand how such an insertion is accommodated in the ribosome, we obtained a cryo-electron microscopy reconstruction of the native large subunit at subnanometer resolution. The insertion site forms a four-way junction that fully preserves the canonical 5S rRNA structure. Moving away from the junction site, the inserted region is conformationally flexible and does not pack tightly against the large subunit.
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Stress factors experienced during space include microgravity, sleep deprivation, radiation, isolation, and microbial contamination, all of which can promote immune suppression (1, 2). Under these conditions, the risk of infection from... more
Stress factors experienced during space include microgravity, sleep deprivation, radiation, isolation, and microbial contamination, all of which can promote immune suppression (1, 2). Under these conditions, the risk of infection from opportunistic pathogens increases significantly, particularly during long-term missions (3). If infection occurs, it is important that the infectious agent should not be antibiotic resistant. Minimizing the occurrence of antibiotic resistance is, therefore, highly desirable. To facilitate this, it is important to better understand the long-term response of bacteria to the microgravity environment. This study demonstrated that the use of antibiotics as a preventive measure could be counterproductive and would likely result in persistent resistance to that antibiotic. In addition, unintended resistance to other antimicrobials might also occur as well as permanent genome changes that might have other unanticipated and undesirable consequences.
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Microorganisms impact spaceflight in a variety of ways. They play a positive role in biological systems, such as waste water treatment but can be problematic through buildups of biofilms that can affect advanced life support. Of special... more
Microorganisms impact spaceflight in a variety of ways. They play a positive role in biological systems, such as waste water treatment but can be problematic through buildups of biofilms that can affect advanced life support. Of special concern is the possibility that during extended missions, the microgravity environment will provide positive selection for undesirable genomic changes. Such changes could affect microbial antibiotic sensitivity and possibly pathogenicity. To evaluate this possibility, Escherichia coli (lac plus) cells were grown for over 1000 generations on Luria Broth medium under low-shear modeled microgravity conditions in a high aspect rotating vessel. This is the first study of its kind to grow bacteria for multiple generations over an extended period under low-shear modeled microgravity. Comparisons were made to a non-adaptive control strain using growth competitions. After 1000 generations, the final low-shear modeled microgravity-adapted strain readily outcom...
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Research Interests: Microbiology, Biology, Fungi, Biodiversity, Medicine, and 15 moreActinobacteria, Humans, Archaea, Bacteria, Cluster Analysis, Microbiome, International Space Station NASA Space Exploration Spaceflight, Microbiota, Controlled Environment Agriculture, Dust, Firmicutes, Cleanroom, Metagenome, Proteobacteria, and Air Microbiology
Morphological variation in the geographically widespread coral Porites lobata can make it difficult to distinguish from other massive congeneric species. This morphological variation could be attributed to geographic variability,... more
Morphological variation in the geographically widespread coral Porites lobata can make it difficult to distinguish from other massive congeneric species. This morphological variation could be attributed to geographic variability, phenotypic plasticity, or a combination of such factors. We examined genetic and microscopic morphological variability in P. lobata samples from the Galápagos, Easter Island, Tahiti, Fiji, Rarotonga, and Australia. Panamanian P. evermanni specimens were used as a previously established distinct outgroup against which to test genetic and morphological methods of discrimination. We employed a molecular analysis of variance (AMOVA) based on ribosomal internal transcribed spacer region (ITS) sequence, principal component analysis (PCA) of skeletal landmarks, and Mantel tests to compare genetic and morphological variation. Both genetic and morphometric methods clearly distinguished P. lobata and P. evermanni, while significant genetic and morphological variance ...
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The microbial ecology of enrichment cultures adapted to the removal of perchlorate and nitrate from high salt solutions and ion-exchange brines was examined over a period of four years using denaturing gradient gel electrophoresis and... more
The microbial ecology of enrichment cultures adapted to the removal of perchlorate and nitrate from high salt solutions and ion-exchange brines was examined over a period of four years using denaturing gradient gel electrophoresis and total DNA extraction with cloning and in each case partial sequencing of the 16S rDNA genes. The cultures studied were a result of enrichment from marine sediment inoculum initiated in 2001. The resulting enrichment cultures were fed perchlorate, or perchlorate and nitrate, in a 3% (w/v) NaCl defined medium or ion-exchange brines (5.6% NaCl) containing perchlorate and nitrate with acetate as the electron donor. All of the sequences' closest matches in the NCBI GenBank database were to marine or salt-tolerant organisms. Strains belonging to the genera Halomonas or Marinobacter were found to dominate in cultures that were fed nitrate in addition to perchlorate, but were effectively absent from cultures fed perchlorate alone. The cultures fed perchlor...
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Research Interests: Crystallography, RNA, Biology, Magnetic Resonance Spectroscopy, Medicine, and 15 moreBiological Sciences, Environmental Sciences, Escherichia coli, Nucleic Acids, Nmr Structure, ribosomal RNA, Hydrogen Bond, Distance Geometry, Functional Group, Base Sequence, Solution Structure, Nucleic Acid Conformation, Ribosomal Protein, Stacking, and Molecular dynamic
The structures of four small RNAs each containing a different version of the UNAC loop were determined in solution using NMR spectroscopy and restrained molecular dynamics. The UMAC tetraloops (where M is A or C) exhibited a typical GNRA... more
The structures of four small RNAs each containing a different version of the UNAC loop were determined in solution using NMR spectroscopy and restrained molecular dynamics. The UMAC tetraloops (where M is A or C) exhibited a typical GNRA fold including at least one hydrogen bond between the first U and fourth C. In contrast, UGAC and UUAC tetraloops have a different orientation of the first and fourth residues, such that they do not closely mimic the GNRA fold. Although the UMAC tetraloops are excellent structural mimics of the GNRA tetraloop backbone, sequence comparisons typically do not reveal co‐variation between the two loop types. The limited covariation is attributed to differences in the location of potential hydrogen bond donors and acceptors as a result of the replacement of the terminal A of GNRA with C in the UMAC version. Thus, UMAC loops do not readily form the common GNRA tetraloop‐receptor interaction. The loop at positions 863‐866 in E. coli 16S ribosomal RNA appear...
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Research Interests: Microbiology, Biology, Medicine, Environmental Change, Biological Sciences, and 14 moreVirulence, Biofilm, Escherichia coli, Stress response, Gene, Anti-Bacterial Agents, Shear Force, Culture Media, Environmental Parameter, BMC, reverse transcriptase polymerase chain reaction, Salmonella enterica, Weightlessness, and Medical and Health Sciences
The draft genome sequences of six Bacillus strains, isolated from the International Space Station and belonging to the Bacillus anthracis-B. cereus-B. thuringiensis group, are presented here. These strains were isolated from the Japanese... more
The draft genome sequences of six Bacillus strains, isolated from the International Space Station and belonging to the Bacillus anthracis-B. cereus-B. thuringiensis group, are presented here. These strains were isolated from the Japanese Experiment Module (one strain), U.S. Harmony Node 2 (three strains), and Russian Segment Zvezda Module (two strains).
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Research Interests: Genetics, Microbiology, Pathology, Molecular Systematics, Medical Microbiology, and 15 moreBiology, Medicine, Cell Culture, DNA, Bacillus, Bacteria, Polymerase Chain Reaction, Bacillus subtilis, Freeze Drying, Bacterial, Base Sequence, Ribosomal DNA, Molecular Sequence Data, Nucleotide sequence, and Department of Pathology and Laboratory Medicine
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Bacillus strains producing highly resistant spores have been isolated from cleanrooms and space craft assembly facilities. Organisms that can survive such conditions merit planetary protection concern and if that resistance can be... more
Bacillus strains producing highly resistant spores have been isolated from cleanrooms and space craft assembly facilities. Organisms that can survive such conditions merit planetary protection concern and if that resistance can be transferred to other organisms, a health concern too. To further efforts to understand these resistances, the complete genome of Bacillus safensis strain FO-36b, which produces spores resistant to peroxide and radiation was determined. The genome was compared to the complete genome of B. pumilus SAFR-032, and the draft genomes of B. safensis JPL-MERTA-8-2 and the type strain B. pumilus ATCC7061. Additional comparisons were made to 61 draft genomes that have been mostly identified as strains of B. pumilus or B. safensis. The FO-36b gene order is essentially the same as that in SAFR-032 and other B. pumilus strains. The annotated genome has 3850 open reading frames and 40 noncoding RNAs and riboswitches. Of these, 307 are not shared by SAFR-032, and 65 are a...
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We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing,... more
We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases ...
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ABSTRACT A device for separating and purifying useful quantities of particles comprises: a. an anolyte reservoir connected to an anode, the anolyte reservoir containing an electrophoresis buffer; b. a catholyte reservoir connected to a... more
ABSTRACT A device for separating and purifying useful quantities of particles comprises: a. an anolyte reservoir connected to an anode, the anolyte reservoir containing an electrophoresis buffer; b. a catholyte reservoir connected to a cathode, the catholyte reservoir also containing the electrophoresis buffer; c. a power supply connected to the anode and cathode; d. a column having a first end inserted into the anolyte reservoir, a second end inserted into the cathode reservoir, and containing a separation medium; e. a light source; f. a first optical fiber having a first fiber end inserted into the separation medium, and having a second fiber end connected to the light source; g. a photo detector h. a second optical fiber having a third fiber end inserted into the separation medium, and having a fouth fiber end connected to the photo detector; and i, an ion-exchange membrane in the anolyte reservoir.
The public availability of over 180,000 bacterial 16S ribosomal RNA (rRNA) sequences has facilitated microbial identification and classification using hybridization and other molecular approaches. In their usual format, such assays are... more
The public availability of over 180,000 bacterial 16S ribosomal RNA (rRNA) sequences has facilitated microbial identification and classification using hybridization and other molecular approaches. In their usual format, such assays are based on the presence of unique subsequences in the target RNA and require a prior knowledge of what organisms are likely to be in a sample. They are thus limited in generality when analyzing an unknown sample.Herein, we demonstrate the utility of catalogs of masses to characterize the bacterial 16S rRNA(s) in any sample. Sample nucleic acids are digested with a nuclease of known specificity and the products characterized using mass spectrometry. The resulting catalogs of masses can subsequently be compared to the masses known to occur in previously-sequenced 16S rRNAs allowing organism identification. Alternatively, if the organism is not in the existing database, it will still be possible to determine its genetic affinity relative to the known organ...
Research Interests: Genetics, Computer Science, Algorithms, Computational Biology, Mass Spectrometry, and 15 moreBiology, Medicine, Biological Sciences, Mathematical Sciences, Bacteria, BMC Bioinformatics, Prior Knowledge, Francisella tularensis, ribosomal RNA, Information Storage and Retrieval, High performance, Base Sequence, Nucleic Acid, Molecular Sequence Data, and ribonuclease
The genomes of Bacillus pumilus SAFR-032 whose spores are highly resistant to UV and the closely related B. pumilus ATCC-7061 that lacks this resistance are compared. Candidate genes are identified that may be responsible for the elevated... more
The genomes of Bacillus pumilus SAFR-032 whose spores are highly resistant to UV and the closely related B. pumilus ATCC-7061 that lacks this resistance are compared. Candidate genes are identified that may be responsible for the elevated resistance.
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Deinococcus phoenicis strain 1P10ME(T) is a radiation- and desiccation-resistant bacterium isolated from a cleanroom facility where the Phoenix Lander spacecraft was assembled. In order to facilitate investigations of the nature of the... more
Deinococcus phoenicis strain 1P10ME(T) is a radiation- and desiccation-resistant bacterium isolated from a cleanroom facility where the Phoenix Lander spacecraft was assembled. In order to facilitate investigations of the nature of the extreme resistance of D. phoenicis to bactericidal factors, a draft genome sequence of D. phoenicis was determined.
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The modern ribosomal machinery is very complex and its core subsystems and many of its individual components are universally found in all three Domains of life. This indicates that much of the story of ribosome origins and its subsequent... more
The modern ribosomal machinery is very complex and its core subsystems and many of its individual components are universally found in all three Domains of life. This indicates that much of the story of ribosome origins and its subsequent evolution predates the last universal common ancestor (LUCA). Thus, ribosome history relates to other early life issues such as the possibility and nature of an RNA World, the early history of chirality, and always most hopefully the origins of the genetic code. However, this is not the end of the story. As discussed elsewhere in this volume, important events have also occurred after LUCA, especially in eukaryotic ribosomes that have served to integrate the machinery with other cellular systems.
Ribosome origins and subsequent evolution are in reality somewhat separate problems. In addressing the former, this chapter initially examines the source and nature of the peptidyl transferase center, (PTC), including where and how the peptide bond is made. This is followed by efforts to understand the subsequent evolution of the ribosome, which led to the addition and refinement of various other functional centers including the decoding center. This is being accomplished using what is in essence is a reverse engineering approach to develop a timeline of major events in the ribosome history. Finally, significant events on the time line are discussed in detail.
Ribosome origins and subsequent evolution are in reality somewhat separate problems. In addressing the former, this chapter initially examines the source and nature of the peptidyl transferase center, (PTC), including where and how the peptide bond is made. This is followed by efforts to understand the subsequent evolution of the ribosome, which led to the addition and refinement of various other functional centers including the decoding center. This is being accomplished using what is in essence is a reverse engineering approach to develop a timeline of major events in the ribosome history. Finally, significant events on the time line are discussed in detail.