[
Methods Cell Biol,
1995]
Compared with other animals, the nematode Caenorhabditis elegans has many advantages for mutant isolation and for genetic analysis. Some of these, for example, small size and rapid growth to high density on inexpensive media, simplify the manipulation of large numbers of animals. Others, such as the lack of a muscle-driven circulatory system and the self-fertilizing hermaphroditic mode of reproduction, enable the survival of strains with genetic defects that would be lethal to more complex animals. Although a few compounds with C. elegans-specific or nematode-specific actions have been described, the vast majority appear to act on targets that are widely distributed in most or all animals, including humans (or even in most or all eukaryotes). As a result, C. elegans has been a popular organism in which to study drug action and there is a substantial body of published work. In this chapter we attempt to extract an underlying feature of this work: the methods that are used in compound-based studies of C. elegans. We present general approaches to evaluating the effects of compounds on C. elegans growth, development, metabolism, and behavior, we discuss strategies for the isolation and analysis of drug-resistant and hypersensitive mutants, and we describe the use of C. elegans for new drug discovery. We also provide, as Table I, a list of some of the compounds already studied in C. elegans, along with one or more references in which information about the detection of compound-specific effects can be found. It is hoped the table will expedite the use of compound-specific mutants as genetic markers...
[
Methods Cell Biol,
1995]
The genetics of Caenorhabditis elegans provides a convenient experimental entry point into many developmental processes and a powerful tool that can be exploited to characterize interactions among a set of genes regulating a particular pathway. Eventually, though, the study of developmental processes becomes a molecular study of gene regulation. At this level, the determination of the on/off state of a gene requires an understanding of not only its transcriptional state, but also post-transcriptional, translational, and post-translational control mechanisms. Although the vertebrate literature is rich in details of factors that influence these regulatory processes, relatively few of the factors responsible for gene expression in the nematode C. elegans have been characterized. This lag in knowledge reflects both the relatively recent arrival of C. elegans on the list of experimental systems, as well as its general unsuitability for biochemistry. There are no tissue culture cell lines established from C. elegans, and it is difficult to isolate, in large amounts, any homogeneous cell type. Moreover, the impermeable eggshell encasing the embryo and the cuticle encasing the worm make pharmacological studies in intact animals difficult and tedious. Grim as this sounds, progress has been made in C. elegans in the field of gene expression. The sensitivity of techniques has improved and the available molecular tool kit has expanded. The study of individual genes has provided descriptions of several regulatory processes, some general and some gene specific. Our current level of understanding of gene regulation is sufficient to say that C. elegans appears, in general, to be a typical eukaryote. As such, C. elegans is amenable to many of the standard analytical approaches used in other developmental systems. The purpose of this chapter is to review our current state of knowledge of transcription and translation in C. elegans (for a review