Postdoc opening in the Avery Lab

Leon Avery leon at EATWORMS.SWMED.EDU
Sat Sep 24 07:13:11 EST 1994

We have an opening for a postdoctoral fellow interested in the
genetics and physiology of excitable cell function in Caenorhabditis
elegans.  Examples of the kinds of projects we're interested in are
given below, but your actual project would be your own choice.  If
you're interested, please send a curriculum vitae, a list of
publications, preprints of any papers in preparation or in press, the
names and addresses of three people who can supply recommendations,
and a cover letter describing your research interests to:

   Leon Avery
   Department of Biochemistry
   University of Texas Southwestern Medical Center
   5323 Harry Hines Blvd
   Dallas, TX 75235-9038

   Fax: (214) 648-8856
   e-mail: leon at


Raizen, DM, and Avery, Leon (1994), "Electrical activity and behavior
in the pharynx of Caenorhabditis elegans", Neuron 12: 483-495.

Avery, Leon (1993), "Genetics of feeding in Caenorhabditis elegans",
Genetics 133: 897-917.

Avery, Leon (1993), "Motor neuron M3 controls pharyngeal muscle
relaxation timing in Caenorhabditis elegans", J Exp Biol 175: 283-297.


1. Motor neuron M4 function and muscle excitability

The pharyngeal motor neuron M4 is usually essential: if you kill it,
worms don't swallow any food, and therefore don't grow.  We recently
discovered conditions under which M4- worms survive.  There are two
tricks.  First you feed the worms baby food--HB101, an E coli strain
that produces a particularly liquid lawn.  Second you depolarize the
pharyngeal muscles.  This can be done either with a drug, arecoline,
or by a mutation, for instance in the worm sodium pump gene eat-6.  If
you use just one of these tricks, about 10% of M4- worms will become
fertile adults.  Using both together boosts the number to 70%.

This means that a mutant in which M4 didn't function would be a
conditional lethal.  The worms would not grow under normal conditions,
but on HB101 and arecoline they would reproduce.  Furthermore,
mutations that depolarize pharyngeal muscles would partially suppress
the lethality of an M4- mutant.

The project has two parts.  The first part is to isolate M4- mutants.
The mutant phenotype is very specific, so this should be a straight-
forward screen.  The mutations would identify genes necessary for M4
action; we know of no such genes now.  The second part of the project
would be to isolate suppressors.  These mutations would identify genes
necessary for the maintenance of pharyngeal muscle resting membrane
potential.  We would expect such genes to include ion pumps and ion

2. Cell-cell coupling and the genetics of ivermectin-resistance

Normally the posterior part of the pharynx, the terminal bulb,
contracts and relaxes in precise synchrony with the anterior part, the
corpus.  This synchronization is probably effected by electrical
coupling, since the muscles are dye-coupled, and corpus and terminal
bulb remain synchronized when all pharyngeal neurons are killed.  The
gene eat-5 was identified by a single mutation, ad464, that uncouples
corpus and terminal bulb contractions (Avery, 1993).  We cloned eat-5
and found that it encodes a protein similar to the C elegans integral
membrane protein UNC-7 and the fly proteins ogre and Passover.
Intriguingly, unc-7 and Passover both affect gap junction connections.
Todd Starrich (who cloned unc-7) has found many additional genes that
belong to this family.

Carl Johnson, studying the genetics of ivermectin resistance, has
found another clue to the function of this gene family.  He selected C
elegans mutants resistant to the anthelminthic ivermectin.  In order
to be strongly resistant, a worm must carry two mutations.  One
mutation must be in the gene avr-15, which we suspect encodes a
glutamate-gated chloride channel.  (Such a channel has been cloned by
Joseph Arena and Doris Cully at Merck.) The other mutation can be in
any one of five genes: avr-14, avr-20, unc-1, unc-9, or unc-7.  The
simplest interpretation of this result is that ivermectin has two
targets, one encoded by avr-15, and one controlled by five genes, one
of which is unc-7.  Either of these targets is sufficient to kill a

An intriguing (although completely speculative) hypothesis is that
this gene family encodes a structural component of an invertebrate gap
junction.  One family of gap junction proteins, the connexins, has
been well characterized.  However, despite looking very hard, no one
has been able to find an invertebrate connexin.

The project would be to investigate the function of this gene family.
First, the genetics of eat-5 need to be worked out.  Since we have
only one eat-5 mutation, we don't know the null phenotype.  Second,
the physiological effects of mutations in the various genes in the
family in the presence and absence of ivermectin would be investi-
gated.  Third, specific hypotheses about gene function might be
investigated by expression in Xenopus oocytes or transgenic worms.

Leon Avery					   (214) 648-2420 (office)
Department of Biochemistry			            -2768 (lab)
University of Texas Southwestern Medical Center             -8856 (fax)
5323 Harry Hines Blvd				   leon at
Dallas, TX  75235-9038

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