<i>Caenorhabditis Elegans</i>
            Functional Genomics in Drug Discovery: Expanding Paradigms

Kaletta, Titus; Butler, L.; Bogaert, Thierry

doi:10.1002/0470014067.ch3

Cited by 4 publications

(2 citation statements)

References 101 publications

(111 reference statements)

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“…7 shows a setup to perform large-scale RNAi and drug screens with time-lapse imaging by combining our sorter, integrated microchambers, and multiwell plate interface chips. Although C. elegans is self-fertilizing and has perhaps the lowest phenotypic variability among multicellular model organisms [12], variations among assayed animals are still present, reducing the robustness of current large-scale screens. Sorting technology can be used to select animals with similar phenotypes (such as fluorescent marker expression levels) before large-scale assays to significantly reduce initial phenotypic variations [12] [13].…”

Section: Screening Strategiesmentioning

confidence: 99%

“…Although C. elegans is self-fertilizing and has perhaps the lowest phenotypic variability among multicellular model organisms [12], variations among assayed animals are still present, reducing the robustness of current large-scale screens. Sorting technology can be used to select animals with similar phenotypes (such as fluorescent marker expression levels) before large-scale assays to significantly reduce initial phenotypic variations [12] [13]. Feature extraction algorithms can be run on animals immobilized in the sorter or the incubation chambers to screen thousands of animals on a single chip.…”

Section: Screening Strategiesmentioning

confidence: 99%

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High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

et al. 2009

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In recent years, the advantages of using small invertebrate animals as model systems for human disease have become increasingly apparent and have resulted in three Nobel Prizes in medicine or chemistry during the last six years for studies conducted on the nematode Caenorhabditis elegans (C. elegans). The availability of a wide array of speciesspecific genetic techniques, along with the transparency of the worm and its ability to grow in minute volumes make C. elegans an extremely powerful model organism. We present a suite of technologies for complex high-throughput wholeanimal genetic and drug screens. We demonstrate a high-speed microfluidic sorter that can isolate and immobilize C. elegans in a well-defined geometry, an integrated chip containing individually addressable screening chambers for incubation and exposure of individual animals to biochemical compounds, and a device for delivery of compound libraries in standard multiwell plates to microfluidic devices. The immobilization stability obtained by these devices is comparable to that of chemical anesthesia and the immobilization process does not affect lifespan, progeny production, or other aspects of animal health. The high-stability enables the use of a variety of key optical techniques. We use this to demonstrate femtosecond-laser nanosurgery and three-dimensional multiphoton microscopy. Used alone or in various combinations these devices facilitate a variety of high-throughput assays using whole animals, including mutagenesis and RNAi and drug screens at subcellular resolution, as well as high-throughput high-precision manipulations such as femtosecond-laser nanosurgery for large-scale in vivo neural degeneration and regeneration studies.

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Section: Screening Strategiesmentioning

confidence: 99%

Section: Screening Strategiesmentioning

confidence: 99%

High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

et al. 2009

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Caenorhabditis elegans: A versatile platform for drug discovery

Artal‐Sanz

Jong

Tavernarakis

2006

Biotechnology Journal

153

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Drug discovery and drug target identification are two intimately linked facets of intervention strategies aimed at effectively combating pathological conditions in humans. Simple model organisms provide attractive platforms for devising and streamlining efficient drug discovery and drug target identification methodologies. The nematode worm Caenorhabditis elegans has emerged as a particularly convenient and versatile tool that can be exploited to achieve these goals. Although C. elegans is a relatively modern addition to the arsenal of model organisms, its biology has already been investigated to an exceptional level. This, coupled with effortless handling and a notable low cost of cultivation and maintenance, allows seamless implementation of high-throughput drug screening approaches as well as in-depth genetic and biochemical studies of the molecular pathways targeted by specific drugs. In this review, we introduce C. elegans as a model organism with significant advantages toward the identification of molecular drug targets. In addition, we discuss the value of the worm in the development of drug screening and drug evaluation protocols. The unique features of C. elegans, which greatly facilitate drug studies, hold promise for both deciphering disease pathogenesis and formulating educated and effective therapeutic interventions.

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C. Elegans Genetic Strategies to Identify Novel Parkinson's Disease-associated Therapeutic Targets and Leads

Nass

2008

Parkinson's Disease

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Caenorhabditis Elegans Functional Genomics in Drug Discovery: Expanding Paradigms

Cited by 4 publications

References 101 publications

High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

High-throughput on-chip in vivo neural regeneration studies using femtosecond laser nano-surgery and microfluidics

Caenorhabditis elegans: A versatile platform for drug discovery

C. Elegans Genetic Strategies to Identify Novel Parkinson's Disease-associated Therapeutic Targets and Leads

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