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.

Public Health Relevance

We aim to develop tools to specifically and efficiently knock out C. elegans genes 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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD075076-02
Application #
8710303
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Coulombe, James N
Project Start
2013-08-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$75,816
Indirect Cost
$27,216
Name
Massachusetts Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139