Development of tissue-specific knockout technologies for C. elegans

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): The nematode Caenorhabditis elegans is an excellent organism for the study of animal development and behavior and of the ways in which mutations can disrupt development and behavior. Numerous methods are available for the genetic manipulation of the C. elegans genome. However, no technologies exist to knock out C. elegans gene functions in a spatially and temporally controlled manner. Such tissue-specific knockout technologies are used routinely in studies of mice and of the fruit fly Drosophila melanogaster. The absence of such a technology makes it difficult to assess in C. elegans the functions of genes in selective cells and tissues, such as neurons, in cases in which general elimination of the functions of these genes results in lethality. By combining a recombinase system, a tetracycline/doxycycline-inducible system, and transcription activator-like effector nuclease (TALEN)-directed genome editing, we aim to develop tools to specifically and efficiently knock out genes in selected tissues of C. elegans in a spatially or temporally controlled manner. We expect that the reagents and approaches we develop will be broadly useful for dissecting the functions of essential genes in C. elegans development and behavior as well as in C. elegans models of human diseases. Sections below that are substantially revised for this resubmission are indicated within brackets.