Biocomputing Postdoc - RNA structure

Michael Zuker zuker at spp.wustl.edu
Thu Nov 7 19:14:36 EST 1996

                     POSTDOC POSTION - Statistical &
                  Algorithmic Aspects of RNA Structure

                   Institute for Biomedical Computing
                         Washington University
                       St.  Louis, MO 63110  USA

   The Institute for Biomedical Computing is an inter-school faculty unit
with a mission to foster the development and application of advanced com-
puting technology to problems in medicine and biology. Institute activities
include research and training collaborations with both the School of Medicine
and the School of Engineering and Applied Science.  The Institute consists
of research laboratory components which have close ties with several depart-
ments in the School of Engineering as well as with most departments in the
School of Medicine.  The Institute now includes the Biomedical Computer
Laboratory (BCL). the Center for Molecular Design (CMD),and the Center
for Computational Biology (CCB).

   Research in the CCB focuses on computational aspects of molecular biol-
ogy including molecular sequence interpretation, RNA structure prediction,
design and analysis of databases of biological information, and analysis of
metabolic systems.  Research involves algorithm development, database de-
sign, and database analysis.

   We are searching for a postdoctoral fellow to work in the CCB under the
direction of Dr. Michael Zuker. For over 15 years, Dr. Zuker has developed
well known algorithms and computer programs for RNA secondary structure
prediction in conjunction with the RNA Biophysical Chemistry Group at the
University of Rochester headed by Professor D. Turner.  During this time,
databases of aligned, homologous RNA sequences have been assembled, and
conserved secondary structures have been deduced by comparative methods
that search for covarying positions.  In particular, a collaboration between
Mike Gray (Dalhousie University, Halifax, NS) and Robin Gutell (University
of Colorado, Boulder) has produced a very large database of small-subunit
and large-subunit rRNA secondary structures.

   There is a wealth of information still hidden within these databases of
RNA secondary structures. In particular, 2 questions can be asked.

  1. Are the frequencies of base pairs and base pair stacking interactions
     random? If not, are they consistent with the thermodynamic rules for
     RNA folding? What is the distribution of loop sizes and the base con-
     tent of single stranded regions? Are these distributions also consistent
     with the thermodynamics? Such studies should shed light on the weak-
     est parts of the thermodynamic parameter set. In particular, valuable
     knowledge should be gained about multi-branched loops.

  2. By computing log-odds ratios for observed frequencies divided by ex-
     pected random frequencies, one can derive "pseudo-energies" or simply
     an empirical set of scoring rules for RNA secondary structure predic-
     tion. This is similar to the derivation of PAM or BLOSSUM matrices
     for protein sequence alignment. Can these empirical rules, used alone
     or together with known thermodynamic parameters, improve existing
     RNA folding algorithms?

   This position would be for 2 (possibly 3) years on the Medical School
campus adjacent to the Department of Biochemistry & Biophysics and the
Department of Genetics.  We offer an open-minded interdisciplinary envi-
ronment.  We are a mostly "Unix shop" with SGIs, Suns, and Dec alphas.
Applicants should have a doctorate in computer science, molecular biology,
or a similar field, with a specialization in computational molecular biology.
Previous experience with problems involving the analysis of biomolecular
sequences and structures would certainly be beneficial.

   Please send application material (including vita, publication list, state-
ment of research interests, and addresses for references) to

Prof. Michael Zuker
Institute for Biomedical Computing
Washington University, Campus Box 8036
700 S. Euclid Avenue
St. Louis, MO 63110

Tel: (314) 362-2932
Fax: (314) 362-0234
E-mail: zuker at ibc.wustl.edu


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