C. elegans genome

Rick K. Wilson rkwilson at JULIET.CALTECH.EDU
Fri Apr 20 13:49:39 EST 1990

(posted for R.H. Waterston, E-mail:  WATERSTO at WUMS.bitnet)

April 20, 1990

Dear Colleague,

     I am writing to solicit your help in identifying outstanding
individuals to join our effort to sequence the 100 Mb genome of the
nematode Caenorhabditis elegans by the end of the decade.  This large
and exciting project is being undertaken jointly by our laboratory in
St. Louis and the laboratory of John Sulston and Alan Coulson of the
MRC Laboratory of Molecular Biology, Cambridge, England.  We are
recruiting now for a pilot project, scheduled for 1990-1993 to
establish methods and yield at least 3 Mb of sequence.  Positions will
be available at several levels, including postdoctoral and
postgraduate, according to the qualifications of the individual.  The
positions, for three years in the first instance, will be available in
early summer.  We would appreciate it if you would give this letter to
anyone you know who might be interested in being a part of this
pathbreaking project.

     As you know, C. elegans is particularly attractive for a genome
sequencing project for several reasons.  The intensive studies in
developmental and cell biology in many labs are making significant
contributions already.  About 1000 loci are placed on the genetic map.
An almost complete physical map has been constructed by the
collaborative efforts of our two groups, and from the efforts of the
C. elegans community, much of this has been correlated with the
genetic map to create a powerful new approach for cloning genes in C.
elegans (see the publications listed below for details of the
mapping).  Importantly, the mapped clones also provide a template for
efficient genome sequencing.  The relatively small DNA content and low
level of repetitive sequences mean that the information density is
high, even in genomic DNA.

     Our intended sequencing strategy relies heavily on the use of
synthetic oligonucleotides to provide controlled start points for
chain termination reactions.  Various methods will be explored to
obtain high quality sequencing templates from the mapped cosmid and
YAC clones.  Automated sequencing machines will be used as much as
possible to provide efficient sequence data collection.  Software will
be developed to organize and coordinate efforts, minimizing labor.
Editing and database management programs will be improved, to speed
assembly of the finished sequence.  We anticipate that analysis of the
sequence through the application of increasingly sophisticated
computer software and hardware will reveal much of the genome's

     An excellent nucleus has already been formed in each location.
In addition to myself at Washington University, Richard K. Wilson will
join us in June from Leroy Hood's lab at CalTech.  He has extensive
experience with automated DNA sequencing and is a leader in the field.
Phil Green of the Genetics Department is leading the St. Louis
software development efforts.  In Cambridge, John Sulston and Alan
Coulson have persuaded Rodger Staden to aid in software development
and have added Molly Craxton to their staff to aid in protocol
development.  We expect to provide for extensive interactions between
the two groups, including visits between labs and exchange of
personnel as appropriate.

     The efforts at each site are supported by excellent related
research activities.  Washington University has several leading groups
in the area of genome analysis, including Maynard Olson's here in the
Genetics Department.  The MRC Laboratory of Molecular Biology has a
long tradition of leadership in methods of DNA sequence determination.
Both institutions have as well excellent research activities in the
biomedical sciences more broadly.  Both provide highly interactive,
supportive environments for research.

     Any interested individuals should send me a description of their
past research experience and  the names, addresses and phone numbers
of two people who can serve as referees, either to me at the above the
address, or to John Sulston, MRC Laboratory of Molecular Biology,
Cambridge, England CB2 2QH.  Informal inquiries by phone are welcome
as well.  My number is 314-362-2657 and John's number is (0223)

     Thanks for your help.

                                             Sincerely yours,

                                             Robert H. Waterston

Coulson, et al., Proc.Nat.Acad.Sci. 83,7821-7825 (1986).
Coulson, et al., Nature 335,184-186 (1988).


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