Research

BACKGROUND:The research in our laboratory uses a model
organism, the small soil nematode Caenorhabditis
elegans, to examine the development and function of the nervous
system.Our main interests are in the
genetics of regulation in the nervous system and how the resultant neuronal
architecture leads to normal neuronal function and behavior.C.
elegans is a wonderful organism for studying the nervous system. It is a
very simple animal: the adult hermaphrodite has 959 somatic cells, including
302 neurons, with known origin, development, and connectivity.C.
elegans are small (1 mm long), transparent, non-obligate hermaphrodites
with a short generation time.They have
a malleable genome with 22,025 sequenced genes.There are thousands of mutants, including many with severe neural
defects, and transgenic animals may be generated rapidly.These properties have allowed us and others
to study the roles of many different proteins and genes in the nervous system.

Cholinergic neurons labeled with GFP in a living C. elegans

CURRENT RESEARCH:Our research uses a variety
of techniques, including genetics, molecular biology, cell biology, and
behavioral assays, to examine the development, distribution, and function of
proteins that are necessary for neurotransmission.In C.
elegans, as in humans, the neurotransmitter acetylcholine is used at
excitatory neuromuscular junctions and is essential for viability.We are examining the regulation and function
of two cholinergic proteins, ChAT (the synthetic enzyme choline
acetyltransferase) and VAChT (the vesicular acetylcholine transporter), in
controlling neurotransmission and behavior.

We are also using mutant
analysis to study monoamine neurotransmitters in this simple animal.In humans, monoamines are important
modulatory neurotransmitters; proteins that alter the uptake and release of
monoamines are targets of several psychoactive drugs.Monoamines are also important for the
modulation of specific behaviors in C.
elegans, including responses to food and egg-laying.We are studying several genes that are
required for normal monoamine levels, including the vesicular monoamine
transporter, the dopamine plasma membrane transporter, the dopamine synthetic
enzyme, and putative monoamine degradation enzymes.In particular, we are interested in how acute
and chronic changes in these proteins alter monoamine-dependent behaviors and
sensitivity to monoamines.What
short-term or developmental changes or compensation occur when dopamine
synthesis, release, re-uptake, or degradation is perturbed?

Panel C:shows the synapses in a mutant, unc-104, that has defects in synaptic
vesicle transport.

A new line of research is directed
at understanding the importance of localized protein synthesis in neuronal
function.Regulation of the subcellular
localization of particular mRNAs has been identified as a critical step in the
control of local protein levels and polarity in many cells, including
neurons.We are adapting a GFP-mRNA
labeling technique to living C. elegans
to identify genes and proteins that are important for the regulation of mRNA
localization and transcription.The
studies will increase our understanding of the complex processes that polarity
in animals.