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  1. Article ; Online: Experimental measurement and computational prediction of bacterial Hanks-type Ser/Thr signaling system regulatory targets.

    Grunfeld, Noam / Levine, Erel / Libby, Elizabeth

    Molecular microbiology

    2024  

    Abstract: Bacteria possess diverse classes of signaling systems that they use to sense and respond to their environments and execute properly timed developmental transitions. One widespread and evolutionarily ancient class of signaling systems are the Hanks-type ... ...

    Abstract Bacteria possess diverse classes of signaling systems that they use to sense and respond to their environments and execute properly timed developmental transitions. One widespread and evolutionarily ancient class of signaling systems are the Hanks-type Ser/Thr kinases, also sometimes termed "eukaryotic-like" due to their homology with eukaryotic kinases. In diverse bacterial species, these signaling systems function as critical regulators of general cellular processes such as metabolism, growth and division, developmental transitions such as sporulation, biofilm formation, and virulence, as well as antibiotic tolerance. This multifaceted regulation is due to the ability of a single Hanks-type Ser/Thr kinase to post-translationally modify the activity of multiple proteins, resulting in the coordinated regulation of diverse cellular pathways. However, in part due to their deep integration with cellular physiology, to date, we have a relatively limited understanding of the timing, regulatory hierarchy, the complete list of targets of a given kinase, as well as the potential regulatory overlap between the often multiple kinases present in a single organism. In this review, we discuss experimental methods and curated datasets aimed at elucidating the targets of these signaling pathways and approaches for using these datasets to develop computational models for quantitative predictions of target motifs. We emphasize novel approaches and opportunities for collecting data suitable for the creation of new predictive computational models applicable to diverse species.
    Language English
    Publishing date 2024-01-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/mmi.15220
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Primer on Mathematical Modeling in C. elegans.

    Ranawade, Ayush / Levine, Erel

    Methods in molecular biology (Clifton, N.J.)

    2022  Volume 2468, Page(s) 375–386

    Abstract: Recently, applications of mathematical and computational models to biological processes have helped investigators to systematically interpret data, test hypotheses built on experimental data, generate new hypotheses, and guide the design of new ... ...

    Abstract Recently, applications of mathematical and computational models to biological processes have helped investigators to systematically interpret data, test hypotheses built on experimental data, generate new hypotheses, and guide the design of new experiments, protocols, and synthetic biological systems. Availability of diverse quantitative data is a prerequisite for successful mathematical modeling. The ability to acquire high-quality quantitative data for a broad range of biological processes and perform precise perturbation makes C. elegans an ideal model system for such studies. In this primer, we examine the general procedure of modeling biological systems and demonstrate this process using the heat-shock response in C. elegans as a case study. Our goal is to facilitate the initial discussion between worm biologists and their potential collaborators from quantitative disciplines.
    MeSH term(s) Animals ; Caenorhabditis elegans ; Models, Biological ; Models, Theoretical
    Language English
    Publishing date 2022-03-23
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-2181-3_21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Microfluidic approaches for

    Levine, Erel / Lee, Kyung Suk

    Animal cells and systems

    2020  Volume 24, Issue 6, Page(s) 311–320

    Abstract: In the last decade, microfluidic methods have proven to be powerful tools ... ...

    Abstract In the last decade, microfluidic methods have proven to be powerful tools for
    Language English
    Publishing date 2020-11-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2562988-8
    ISSN 2151-2485 ; 1976-8354
    ISSN (online) 2151-2485
    ISSN 1976-8354
    DOI 10.1080/19768354.2020.1837951
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Lessons Learned from Two Decades of Modeling the Heat-Shock Response.

    Ranawade, Ayush / Sharma, Rati / Levine, Erel

    Biomolecules

    2022  Volume 12, Issue 11

    Abstract: The Heat Shock Response (HSR) is a highly conserved genetic system charged with protecting the proteome in a wide range of organisms and species. Experiments since the early 1980s have elucidated key elements in these pathways and revealed a canonical ... ...

    Abstract The Heat Shock Response (HSR) is a highly conserved genetic system charged with protecting the proteome in a wide range of organisms and species. Experiments since the early 1980s have elucidated key elements in these pathways and revealed a canonical mode of regulation, which relies on a titration feedback. This system has been subject to substantial modeling work, addressing questions about resilience, design and control. The compact core regulatory circuit, as well as its apparent conservation, make this system an ideal 'hydrogen atom' model for the regulation of stress response. Here we take a broad view of the models of the HSR, focusing on the different questions asked and the approaches taken. After 20 years of modeling work, we ask what lessons had been learned that would have been hard to discover without mathematical models. We find that while existing models lay strong foundations, many important questions that can benefit from quantitative modeling are still awaiting investigation.
    MeSH term(s) Heat-Shock Response/genetics ; Proteome/metabolism
    Chemical Substances Proteome
    Language English
    Publishing date 2022-11-07
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12111645
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Microfluidic approaches for Caenorhabditis elegans research

    Erel Levine / Kyung Suk Lee

    Animal Cells and Systems, Vol 24, Iss 6, Pp 311-

    2020  Volume 320

    Abstract: In the last decade, microfluidic methods have proven to be powerful tools for Caenorhabditis elegans research, offering advanced manipulation of worms and precise control of experimental conditions. The advantages of microfluidic chips include their ... ...

    Abstract In the last decade, microfluidic methods have proven to be powerful tools for Caenorhabditis elegans research, offering advanced manipulation of worms and precise control of experimental conditions. The advantages of microfluidic chips include their capability of immobilization, automated sorting, and longitudinal measurement, and more. In this review, we focus on control components that are widely used in the design of microfluidic devices, and discuss their functions and working principles that enable advanced manipulation on a chip. Understanding these components will ease the onboarding of researchers inexperienced with microfluidics and help them bring the power of microfluidics to new applications.
    Keywords c. elegans ; microfluidics ; immobilization ; sorting ; automation ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Taylor & Francis Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Microfluidic approaches for Caenorhabditis elegans research

    Levine, Erel / Lee, Kyung Suk

    Animal cells and systems. 2020 Nov. 01, v. 24, no. 6

    2020  

    Abstract: In the last decade, microfluidic methods have proven to be powerful tools for Caenorhabditis elegans research, offering advanced manipulation of worms and precise control of experimental conditions. The advantages of microfluidic chips include their ... ...

    Abstract In the last decade, microfluidic methods have proven to be powerful tools for Caenorhabditis elegans research, offering advanced manipulation of worms and precise control of experimental conditions. The advantages of microfluidic chips include their capability of immobilization, automated sorting, and longitudinal measurement, and more. In this review, we focus on control components that are widely used in the design of microfluidic devices, and discuss their functions and working principles that enable advanced manipulation on a chip. Understanding these components will ease the onboarding of researchers inexperienced with microfluidics and help them bring the power of microfluidics to new applications.
    Keywords Caenorhabditis elegans ; cells ; control components ; design ; measurement ; microfluidic technology ; research ; researchers ; sorting
    Language English
    Dates of publication 2020-1101
    Size p. 311-320.
    Publishing place Taylor & Francis
    Document type Article
    Note NAL-light
    ZDB-ID 2562988-8
    ISSN 2151-2485 ; 1976-8354
    ISSN (online) 2151-2485
    ISSN 1976-8354
    DOI 10.1080/19768354.2020.1837951
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: A Microfluidic Platform for Longitudinal Imaging in Caenorhabditis elegans.

    Lee, Kyung Suk / Levine, Erel

    Journal of visualized experiments : JoVE

    2018  , Issue 135

    Abstract: In the last decade, microfluidic techniques have been applied to study small animals, including the nematode Caenorhabditis elegans, and have proved useful as a convenient live imaging platform providing capabilities for precise control of experimental ... ...

    Abstract In the last decade, microfluidic techniques have been applied to study small animals, including the nematode Caenorhabditis elegans, and have proved useful as a convenient live imaging platform providing capabilities for precise control of experimental conditions in real time. In this article, we demonstrate live imaging of individual worms employing WormSpa, a previously-published custom microfluidic device. In the device, multiple worms are individually confined to separate chambers, allowing multiplexed longitudinal surveillance of various biological processes. To illustrate the capability, we performed proof-of-principle experiments in which worms were infected in the device with pathogenic bacteria, and the dynamics of expression of immune response genes and egg laying were monitored continuously in individual animals. The simple design and operation of this device make it suitable for users with no previous experience with microfluidic-based experiments. We propose that this approach will be useful for many researchers interested in longitudinal observations of biological processes under well-defined conditions.
    MeSH term(s) Animals ; Caenorhabditis elegans/chemistry ; Lab-On-A-Chip Devices/statistics & numerical data ; Microfluidic Analytical Techniques/instrumentation ; Microfluidic Analytical Techniques/methods
    Language English
    Publishing date 2018-05-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/57348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A microfluidic platform for longitudinal imaging in Caenorhabditis elegans

    Lee, Kyung Suk / Levine, Erel

    Journal of visualized experiments. 2018 May 02, , no. 135

    2018  

    Abstract: In the last decade, microfluidic techniques have been applied to study small animals, including the nematode Caenorhabditis elegans, and have proved useful as a convenient live imaging platform providing capabilities for precise control of experimental ... ...

    Abstract In the last decade, microfluidic techniques have been applied to study small animals, including the nematode Caenorhabditis elegans, and have proved useful as a convenient live imaging platform providing capabilities for precise control of experimental conditions in real time. In this article, we demonstrate live imaging of individual worms employing WormSpa, a previously-published custom microfluidic device. In the device, multiple worms are individually confined to separate chambers, allowing multiplexed longitudinal surveillance of various biological processes. To illustrate the capability, we performed proof-of-principle experiments in which worms were infected in the device with pathogenic bacteria, and the dynamics of expression of immune response genes and egg laying were monitored continuously in individual animals. The simple design and operation of this device make it suitable for users with no previous experience with microfluidic-based experiments. We propose that this approach will be useful for many researchers interested in longitudinal observations of biological processes under well-defined conditions.
    Keywords Caenorhabditis elegans ; animals ; genes ; image analysis ; immune response ; monitoring ; oviposition ; virulent strains
    Language English
    Dates of publication 2018-0502
    Size p. e57348.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/57348
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Sort-seq under the hood: implications of design choices on large-scale characterization of sequence-function relations.

    Peterman, Neil / Levine, Erel

    BMC genomics

    2016  Volume 17, Page(s) 206

    Abstract: Background: Sort-seq is an effective approach for simultaneous activity measurements in a large-scale library, combining flow cytometry, deep sequencing, and statistical inference. Such assays enable the characterization of functional landscapes at ... ...

    Abstract Background: Sort-seq is an effective approach for simultaneous activity measurements in a large-scale library, combining flow cytometry, deep sequencing, and statistical inference. Such assays enable the characterization of functional landscapes at unprecedented scale for a wide-reaching array of biological molecules and functionalities in vivo. Applications of sort-seq range from footprinting to establishing quantitative models of biological systems and rational design of synthetic genetic elements. Nearly as diverse are implementations of this technique, reflecting key design choices with extensive impact on the scope and accuracy the results. Yet how to make these choices remains unclear. Here we investigate the effects of alternative sort-seq designs and inference methods on the information output using mathematical formulation and simulations.
    Results: We identify key intrinsic properties of any system of interest with practical implications for sort-seq assays, depending on the experimental goals. The fluorescence range and cell-to-cell variability specify the number of sorted populations needed for quantitative measurements that are precise and unbiased. These factors also indicate cases where an enrichment-based approach that uses a single sorted population can offer satisfactory results. These predications of our model are corroborated using re-analysis of published data. We explore implications of these results for quantitative modeling and library design.
    Conclusions: Sort-seq assays can be streamlined by reducing the number of sorted populations, saving considerable resources. Simple preliminary experiments can guide optimal experiment design, minimizing cost while maintaining the maximal information output and avoiding latent biases. These insights can facilitate future applications of this highly adaptable technique.
    MeSH term(s) Computer Simulation ; Flow Cytometry ; Gene Library ; High-Throughput Nucleotide Sequencing/methods ; Likelihood Functions ; Models, Genetic ; Mutation ; Sequence Analysis, RNA/methods
    Language English
    Publishing date 2016-03-09
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1471-2164
    ISSN (online) 1471-2164
    DOI 10.1186/s12864-016-2533-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A Primer on Quantitative Modeling.

    Neagu, Iulia / Levine, Erel

    Methods in molecular biology (Clifton, N.J.)

    2015  Volume 1327, Page(s) 241–250

    Abstract: Caenorhabditis elegans is particularly suitable for obtaining quantitative data about behavior, neuronal activity, gene expression, ecological interactions, quantitative traits, and much more. To exploit the full potential of these data one seeks to ... ...

    Abstract Caenorhabditis elegans is particularly suitable for obtaining quantitative data about behavior, neuronal activity, gene expression, ecological interactions, quantitative traits, and much more. To exploit the full potential of these data one seeks to interpret them within quantitative models. Using two examples from the C. elegans literature we briefly explore several types of modeling approaches relevant to worm biology, and show how they might be used to interpret data, formulate testable hypotheses, and suggest new experiments. We emphasize that the choice of modeling approach is strongly dependent on the questions of interest and the type of available knowledge.
    MeSH term(s) Animals ; Behavior, Animal ; Caenorhabditis elegans/physiology ; Computer Simulation ; Models, Biological
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-2842-2_18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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