Tal Elad

University of California, Berkeley, Berkeley, California, United States

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Publications (15)46 Total impact

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    ABSTRACT: Dispersal limitation in phyllosphere communities was measured on the leaf surfaces of salt-excreting Tamarix trees, which offer unique, discrete habitats for microbial assemblages. We employed 16S rRNA gene pyrosequencing to measure bacterial community dissimilarity on leaves of spatially dispersed Tamarix specimens in sites with uniform climatic conditions across the Sonoran Desert in the Southwestern United States. Our analyses revealed diverse bacterial communities with four dominant phyla that exhibited differential effects of environmental and geographic variables. Geographical distance was the most important parameter that affected community composition, particularly that of betaproteobacteria, which displayed a statistically significant, distance-decay relationship.
    Applied and Environmental Microbiology 06/2012; 78(17):6187-93. DOI:10.1128/AEM.00888-12 · 3.95 Impact Factor
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    ABSTRACT: An international round-robin study on the Ames fluctuation test [ISO 11350, 2012], a microplate version of the classic plate-incorporation method for the detection of mutagenicity in water, wastewater and chemicals was performed by 18 laboratories from seven countries. Such a round-robin study is a precondition for both the finalization of the ISO standardization process and a possible regulatory implementation in water legislation. The laboratories tested four water samples (spiked/nonspiked) and two chemical mixtures with and without supplementation of a S9-mix. Validity criteria (acceptable spontaneous and positive control-induced mutation counts) were fulfilled by 92-100%, depending on the test conditions. A two-step method for statistical evaluation of the test results is proposed and assessed in terms of specificity and sensitivity. The data were first subjected to powerful analysis of variance (ANOVA) after an arcsine-square-root transformation to detect significant differences between the test samples and the negative control (NC). A threshold (TH) value based on a pooled NC was then calculated to exclude false positive test results. Statistically, positive effects observed by the William's test were considered negative, if the mean of all replicates of a sample did not exceed the calculated TH. By making use of this approach, the overall test sensitivity was 100%, and the test specificity ranged from 80 to 100%.
    Environmental and Molecular Mutagenesis 04/2012; 53(3):185-97. DOI:10.1002/em.21677 · 2.55 Impact Factor
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    ABSTRACT: The ever-growing use of pharmaceutical compounds, including antibacterial substances, poses a substantial pollution load on the environment. Such compounds can compromise water quality, contaminate soils, livestock and crops, enhance resistance of microorganisms to antibiotic substances, and hamper human health. We report the construction of a novel panel of genetically engineered Escherichia coli reporter strains for the detection and classification of antibiotic substances. Each of these strains harbours a plasmid that carries a fusion of a selected gene promoter to bioluminescence (luxCDABE) reporter genes and an alternative tryptophan auxotrophy-based non-antibiotic selection system. The bioreporter panel was tested for sensitivity and responsiveness to diverse antibiotic substances by monitoring bioluminescence as a function of time and of antibiotic concentrations. All of the tested antibiotics were detected by the panel, which displayed different response patterns for each substance. These unique responses were analysed by several algorithms that enabled clustering the compounds according to their functional properties, and allowed the classification of unknown antibiotic substances with a high degree of accuracy and confidence.
    Microbial Biotechnology 03/2012; 5(4):536-48. DOI:10.1111/j.1751-7915.2012.00333.x · 3.21 Impact Factor
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    Tal Elad, Shimshon Belkin
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    ABSTRACT: Chip-integrated luminescent recombinant reporter bacteria were combined with fluidics and light detection systems to form a real-time water biomonitor. The biomonitor was exposed to a continuous water flow for up to ten days, in the course of which it was challenged with spikes of both model toxic compounds and toxic environmental samples. All simulated contamination events were reported within 0.5-2.5 h. Furthermore, the response pattern of the reporter bacteria was indicative of the nature of the contaminating chemicals. Efforts were aimed at improving signal quality and at the development of an alarm management software. Following further research, a device of the proposed design could be implemented in monitoring networks as an early warning system against water pollution by toxic chemicals.
    Bioengineered bugs 03/2012; 3(2):124-8. DOI:10.4161/bbug.18879
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    ABSTRACT: An international round-robin study on the Ames fluctuation test [ISO 11350, 2012], a microplate version of the classic plate-incorporation method for the detection of mutagenicity in water, wastewater and chemicals was performed by 18 laboratories from seven countries. Such a round-robin study is a precondition for both the finalization of the ISO standardization process and a possible regulatory implementation in water legislation. The laboratories tested four water samples (spiked/nonspiked) and two chemical mixtures with and without supplementation of a S9-mix. Validity criteria (acceptable spontaneous and positive control-induced mutation counts) were fulfilled by 92-100%, depending on the test conditions. A two-step method for statistical evaluation of the test results is proposed and assessed in terms of specificity and sensitivity. The data were first subjected to powerful analysis of variance (ANOVA) after an arcsine-square-root transformation to detect significant differences between the test samples and the negative control (NC). A threshold (TH) value based on a pooled NC was then calculated to exclude false positive test results. Statistically, positive effects observed by the William's test were considered negative, if the mean of all replicates of a sample did not exceed the calculated TH. By making use of this approach, the overall test sensitivity was 100%, and the test specificity ranged from 80 to 100%. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
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    ABSTRACT: Motivated by the advantages endowed by high-throughput analysis, researchers have succeeded in incorporating multiple reporter cells into a single platform; the technology now allows the simultaneous scrutiny of a large collection of sensor strains. We review current aspects in cell array technology with emphasis on microbial sensor arrays. We consider various techniques for patterning live cells on solid surfaces, describe different array-based applications and devices, and highlight recent efforts for live cell storage. We review mathematical approaches for deciphering the data emanating from bioreporter collections, and discuss the future of single cell arrays. Innovative technologies for cell patterning, preservation and interpretation are continuously being developed; when they all mature, cell arrays may become an efficient analytical tool, in a scope resembling that of DNA microarray biochips.
    Current Opinion in Biotechnology 12/2011; 23(1):2-8. DOI:10.1016/j.copbio.2011.11.024 · 8.04 Impact Factor
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    ABSTRACT: We describe a flow-through biosensor for online continuous water toxicity monitoring. At the heart of the device are disposable modular biochips incorporating agar-immobilized bioluminescent recombinant reporter bacteria, the responses of which are probed by single-photon avalanche diode detectors. To demonstrate the biosensor capabilities, we equipped it with biochips harboring both inducible and constitutive reporter strains and exposed it to a continuous water flow for up to 10 days. During these periods we challenged the biosensor with 2-h pulses of water spiked with model compounds representing different classes of potential water pollutants, as well as with a sample of industrial wastewater. The biosensor reporter panel detected all simulated contamination events within 0.5-2.5 h, and its response was indicative of the nature of the contaminating chemicals. We believe that a biosensor of the proposed design can be integrated into future water safety and security networks, as part of an early warning system against accidental or intentional water pollution by toxic chemicals.
    Environmental Science & Technology 08/2011; 45(19):8536-44. DOI:10.1021/es202465c · 5.48 Impact Factor
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    ABSTRACT: Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by microsystem- technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the microelectronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.
    Current Pharmaceutical Biotechnology 06/2010; 11(4):376-383. DOI:10.2174/138920110791233325 · 2.51 Impact Factor
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    ABSTRACT: Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by micro-system-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the micro-electronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.
    Current pharmaceutical biotechnology 03/2010; 11(4):376-83. · 2.51 Impact Factor
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    ABSTRACT: The coming of age of whole-cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines - the whole cell array. In the present chapter, we highlight the state-of-the-art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals, and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high-performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis, and - most importantly - enhanced long term maintenance of viability and activity on the fabricated biochips.
    Advances in biochemical engineering/biotechnology 01/2010; 117:85-108. DOI:10.1007/10_2009_16 · 2.60 Impact Factor
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    ABSTRACT: Bioluminescence-based whole cell biosensors are devices that can be very useful for environmental monitoring applications. The advantages of these devices are that they can be produced as a single-chip, low-power, rugged, inexpensive component, and can be deployed in a variety of non-laboratory settings. However, such biosensors encounter inherent problems in overall system light collection efficiency. The light emitted from the bioluminescent microbial cells is isotropic and passes through various media before it reaches the photon detectors. We studied the bioluminescence distribution and propagation in microbial whole cell biochips. Optical emission and detection were modeled and simulated using an optical ray tracing method. Light emission, transfer and detection were simulated and optimized with respect to two fundamental system parameters: system geometry and bacterial concentration. Optimization elucidated some of the optical aspects of the biochip, e.g. detector radius values between 300 and 750 μm, and bacterial fixation radius values between 800 and 1200 μm. Understanding theses aspects may establish a basis for future optimization of similar chips.
    Biosensors & Bioelectronics 03/2009; DOI:10.1016/j.bios.2008.10.035 · 6.45 Impact Factor
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    ABSTRACT: Genetically engineered microorganisms, tailored to respond by a dose-dependent signal to the presence of toxic chemicals, are a potentially useful tool for environmental monitoring. One manifestation of this approach is based on a panel of luminescent bacterial bioreporters, harboring fusions of the luxCDABE operon to various stress-responsive gene promoters. Such sensors can report by a dose-dependent luminescent signal on the stress sensed by the cells and thus on the presence of toxic compound(s), but they lack the ability to identify the chemicals involved. Here, we demonstrate how the use of a panel of such sensors might offer a solution to this drawback. Five selected Escherichia coli reporter strains harboring fusions of selected gene promoters (grpE, nhoA, oraA, lacZ, and mipA) to luxCDABE were exposed to five model toxicants and to a toxicant-free control in a 40-repetition format. Each of the six treatments activated different promoters to different extents, producing its own unique fingerprint. Two machine learning schemes were challenged with the obtained data set: Bayesian decision theory and the nonparametric nearest-neighbor technique. The Bayesian classifiers performed better and were able to identify the sample's contents within 30 min with an error rate estimate that did not exceed 3% at a 95% confidence level and with zero false negatives. Performance in tap water and wastewater samples was similar. Given the coming of age of whole-cell sensing devices, pattern classification algorithms such as the ones described here offer a step toward the incorporation of reporter cells into future biosensor formats, including whole-cell arrays.
    Environmental Science and Technology 12/2008; 42(22):8486-91. DOI:10.1021/es801489a · 5.48 Impact Factor
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    ABSTRACT: The coming of age of whole-cell biosensors, combined with the continuing advances in array technologies, has prepared the ground for the next step in the evolution of both disciplines - the whole-cell array. In the present review, we highlight the state-of-the-art in the different disciplines essential for a functional bacterial array. These include the genetic engineering of the biological components, their immobilization in different polymers, technologies for live cell deposition and patterning on different types of solid surfaces, and cellular viability maintenance. Also reviewed are the types of signals emitted by the reporter cell arrays, some of the transduction methodologies for reading these signals and the mathematical approaches proposed for their analysis. Finally, we review some of the potential applications for bacterial cell arrays, and list the future needs for their maturation: a richer arsenal of high-performance reporter strains, better methodologies for their incorporation into hardware platforms, design of appropriate detection circuits, the continuing development of dedicated algorithms for multiplex signal analysis and - most importantly - enhanced long-term maintenance of viability and activity on the fabricated biochips.
    Microbial Biotechnology 03/2008; 1(2):137-48. DOI:10.1111/j.1751-7915.2007.00021.x · 3.21 Impact Factor
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    ABSTRACT: A novel micro-fluidic whole cell biosensor for toxicity analysis based on bioluminescence detection was developed. The optical part of the biochip was modelled and simulated to optimize the total light collection efficiency and the system response. The optimization elucidated some of the optical aspects of the biochip. A study evaluating the bioluminescence reaction kinetics was performed and revealed the interdependence between the detected bioluminescence and the physical parameters of the introduced toxin.
    The 11th International Conference on Miniaturized Systems for Chemistry and Life Sciences (μTAS 2007); 10/2007
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    ABSTRACT: In this work we present a mathematical model for the bioreporter activity of an E. coli based bioluminescent bioreporter. This bioreporter is based on a genetically modified E. coli which harbors the recA promoter, a member of the bacterial SOS response, fused to the bacterial luminescence (lux) genes. This bioreporter responds to the presence of DNA damaging agents such as heavy metals, H2O2 and Nalidixic Acid (NA) that activate the SOS response. In our mathematical model we implemented basic physiological mechanisms such as: the penetration of the NA into the biosensor; gyrase enzyme inhibition by the NA; gyrase level regulation; creation of chromosomal DNA damage; DNA repair and release of ssDNA into the cytoplasm; SOS induction and chromosomal DNA repair; activation of lux genes by the fused recA promoter carried on a plasmidal DNA; transcription and translation of the luminescence responsible enzymes; luminescence cycle; energy molecules level regulation and the regulation of the O2 consumption. The mathematical model was defined using a set of ordinary differential equations (ODE) and solved numerically. We simulated the system for different con-centrations of NA in water for specific biosensors concentration, and under limited O2 conditions. The simulated results were compared to experimental data and satisfactory matching was obtained. This manuscript presents a proof of concept showing that real biosensors can be modeled and simulated. This sets the ground to the next stage of implementing a comprehensive physiological model using experimentally extracted parameters. Following the completion of the next stage, it will be possible to construct a "Computer Aided Design" tool for the simulation of the genetically engineered biosensors. We define a term "bioCAD" for a Biological System Computer Aided Design. The specific bioCAD that is described here is aimed towards whole cell biosensors which are under investigation today for functional sensing. Usage of the bioCAD will improve the biosensors design process and boost their performance. It will also reduce Non Recurring Engineering (NRE) cost and time. Finally, using a parameterized solution will allow fair and quick evaluation of whole cell biosensors for various applications.