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Fostering new paradigms for the biological sciences

EDWARD J. SAMBRISKI

Chemical and Biological Engineering

Faculty Advisor: Juan de Pablo

sambriski@wisc.edu


Resume 2007

 
 

Edward Sambriski

Despite their simplicity, bacteriophage are viral agents having the
specialized ability of manipulating and controlling deoxyribonucleic
acid (DNA) molecules in a very precise manner. Prior to attacking a
host cell, and crucial to their proliferation, bacteriophage first
package their genome into a container, or capsid, having a spatial
dimension comparable to the smallest characteristic length scale of
DNA. The packaging step represents a remarkable feat mediated by a
biological motor, which must overcome a large, resistive force as the
amount of loaded DNA reaches the entirety of the viral genome, making
this one of the most powerful molecular motors known to date. While
only the first and last snapshots of the process (unpackaged and
packaged DNA, respectively) have been captured by experiments, the
in-between images have yet to be acquired to understand the mechanism
behind DNA packing in capsids, and more specifically, the operation of
the molecular motor.

My project in Juan de Pablo's group aims to address the in-between
snapshots of bacteriophage packing, and follow through the subsequent
stages of viral infection, by using computer simulation methods.
Several considerations that will be given to the problem include
geometrical requirements, associated forces and pressures in the
system, and the effects of hydrodynamics, salt concentration, as well
as electrostatic interactions on the process. For convenience and
practicality, most computational work done previously in this area
employ a heavily coarse-grained model that is likely to overlook
essential details in describing the formation of the genome/capsid
co-assembly on smaller length scales. We propose to use an improved
mesoscopic model for DNA to help answer questions posed by the viral
packaging problem and provide insights for future experimental work.
Our understanding of the operation of the molecular motor and the
interactions of the genome with the capsid will shed light on the
general problem of exonucleolytic manipulation of DNA, such as in the
design and optimization of nanoscopic devices for biotechnological
applications.

 

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