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FRISC: The Faculty Research Interests Science Comparator |
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Associate Professor of Molecular Biology
Genetics and
Development
Neuroscience
Office: (214) 648-1488
FAX: (214) 648-1488
Email: leon@eatworms.swmed.edu
We are trying to understand how electrically excitable cells such as nerve and muscle
cells work. Excitable cells have voltage-gated ion channels in their membranes, which open
to let charged ions enter or leave the cell. These ion channels come in many types, not
all of them known. Moreover, ion channels are controlled in complicated ways so as to give
the right behavior at the right time in the right cell. We're trying to put this all
together: to understand how the electrical properties of a particular set of nerve cells
and muscles come about, and how they work together to produce normal behavior. In essence,
we're trying to understand behavior right down to the molecules.
Such an attempt is possible only by choosing a simple, tractable behavior. We are
studying feeding in the soil roundworm Caenorhabditis elegans . Feeding is
accomplished by an organ called the pharynx, a neuromuscular pump that sucks bacteria into
the worm. The pharynx contains just 20 muscle cells and 20 neurons. We have three main
ways of figuring out how it works. First, we can use electrophysiological methods to study
the electrical properties of cells and molecules. Second, we can make mutations in genes
that control the electrical activity of pharyngeal muscle or nerve cells. Third, we can
kill neurons with a laser microbeam. By looking at how the electrical signals and behavior
change when we kill particular neurons, we can figure out what they contribute to
behavior. By looking at how things change when we make mutations in particular genes, we
can figure out what the genes contribute.
Three types of neurons turn out to be crucial for controlling movement. One tells the
muscles when to contract, one tells them when to relax, and one tells a particular muscle
when it should carry out a swallowing motion. These three types of neurons are regulated
by the others, and two of the three are also sensory, so that, for instance, the worm will
pump more when there's food around. We have found some genes that are necessary for these
neurons to work and several genes that are necessary for proper control of muscle
electrical activity. Four of these genes encode key ion channels that control the muscle
action potential. Others encode molecules such as G proteins that are involved in
neuromuscular signaling.
Selected Publications:
Dent, JA, Smith, MM, Vassilatis, D, Avery, L (1999), Genetics of ivermectin
resistance in C. elegans , in preparation.
Davis, MW, Fleischauer, R, Dent, JA, Joho, RH, Avery, L (1999), Mutations in
EXP-2, a Kv-type K + channel with HERG-like kinetics, affect behavior in C
elegans , submitted.
Lee, RYN, Sawin, B, Horvitz, HR, Avery, L (1998), EAT-4, a sodium-dependent
inorganic phosphate cotransporter homolog, is necessary for glutamatergic
neurotransmission in Caenorhabditis elegans , J
Neurosci 19: 159-167.
Goodman, MB, Hall, DH, Avery, L, Lockery, SR (1998), Active currents regulate
sensitivity and dynamic range in C elegans
neurons Neuron 20: 763-772.
Lee, RYN, Lobel, L, Hengartner, M, Horvitz, HR, Avery, Leon (1997), Mutations in
the a 1 subunit of an L-type voltage-activated Ca 2+
channel cause myotonia in Caenorhabditis elegans ,
EMBO J 16:
6066-6076.
Dent, JA, Davis, MW, and Avery, L (1997), The avr-15
encoded chloride channel subunit mediates ivermectin sensitivity in C elegans , EMBO J 16:
5867-5879.
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Eliminated words list: MedlinePlus List
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Database: Medline abstracts (1967 - Present)
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Results computed on: 6/9/2006