Title: Designing Useful Viruses

Speaker:  Steven Skiena
SUNY Stony Brook


Date: Friday, February 20, 2009
Time 11:00-11:50
Venue: Room 3464, HKUST

Abstract: 
Tremendous advances have been made in reducing the cost of DNA synthesis
for long sequences since the first genome-level synthesis of a virus
(poliovirus) by Cello, Paul, and Wimmer in July 2002.   We are entering an
age of synthetic biology, where we can design and synthesize new life forms
for scientific and medical applications.

Our group has designed, synthesized, and evaluated several new variants of
poliovirus to serve as models for possible vaccines. Specifically, we seek
weakened but viable strains that may be used for preparations of a killed
poliovirus vaccine, a point of tremendous significance in the context of the
ongoing global polio eradication.  Our designs result in a viruses with roughly
100 fold lower specific infectivity than the wildtype virus.

We have developed several novel algorithms for gene design, which optimize
the DNA sequence for particular desired properties while simultaneously
coding for the given amino acid sequence.  Our most recent work [1] revolves
around designs which optimize the codon-pair bias of a sequence to modulate
expression.  In our earlier work,  we have developedalgorithms for maximizing
or minimizing the desired RNA secondary structure in the sequence as well as
maximally adding and/or removing specified sets of patterns.  The former issue
arises in designing viable viruses, while the later is useful to
optimally insert restriction
sites for technological reasons.  We have also studied the extent to
which overlapping
genes can be designed which simultaneously encode two or more genes in
alternate reading frames.   This amazing property occurs often in viruses,
and can be exploited for technological purposes such as interleaving
antibiotic resistance genes.

In this talk, I will discuss (1) our experiences with designing and
synthesizing these virus variants, (2) review emerging technologies for
large-scale synthesis, and (3) provide an overview of sequence design algorithms
and directions for future work.

[1] J.R. Coleman, D. Papamichial, S. Skiena, B. Futcher, S. Mueller,
and E. Wimmer,
Virus attenuation by genome-scale changes in codon-pair bias, Science
320 (2008) 1784-1787.



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Biography: Steven Skiena is Professor of Computer Science at SUNY Stony Brook.
His research interests include the design of graph, string, and geometric
algorithms, and their applications (particularly to biology).  He is the
author of four books, including "The Algorithm Design Manual" and
"Calculated Bets: Computers, Gambling, and Mathematical Modeling to Win".
He is recipient of the ONR Young Investigator Award and the
IEEE Computer Science and Engineering Undergraduate Teaching Award.