How do genes control animal development and
behavior? To answer this question, we isolate developmental and behavioral
mutants of the nematode Caenorhabditis elegans and use genetic,
molecular, cell biological, pharmacological, electrophysiological
and biochemical techniques to characterize these mutants and the genes
defined by them. Because the complete cellular anatomy (including
the complete wiring of the 302-cell nervous system) and the complete
cell lineage of C. elegans are known, mutant animals can be
studied at the level of single cells and even single synapses. Because
the complete DNA sequence of the C. elegans genome is available,
genes defined by mutations can be rapidly cloned and analyzed. In
addition, genes and complete gene families defined by sequences similar
to those of known genes (e.g., from C. elegans or from other
organisms, including humans) can be easily identified and inactivated
by isolating deletion mutations and by using the method of RNA-mediated
interference (RNAi). Many of our current interests derive from our
earlier studies of the control of C. elegans egg laying, which
led us to isolate mutants defective in egg laying and then analyze
the roles of the genes defined by these mutants in the development
and functioning of the egg-laying system and elsewhere in the animal.
We have studied many genes that play specific roles in C. elegans
development and behavior, including defining members of the POU and
LIM transcription factor families and of the RGS signal transduction
protein family. These protein families have since been found to play
major roles in a variety of biological processes in many organisms.
We discovered heterochronic genes (which control developmental timing),
defined the core caspase-mediated pathway for programmed cell death
(apoptosis) and helped elucidate the Ras pathway for signal transduction.
Our work has defined biological mechanisms and pathways that have
subsequently been found to be shared among organisms as diverse as
nematodes and humans and that have been implicated in a variety of
human diseases.
