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UNRAVELING THE MYSTERY OF HOW VIRUSES FORM: UF PROFESSOR MAKES HEADWAY WITH COMPUTER SIMULATION AND MODELS

April 12, 2004

GAINESVILLE, Fla. --- Dr. Meera Sitharam is using geometry, computer simulation, and modeling to approach the age-old problem among scientists about how biological viruses form. "There has been much work on the study of viruses since the l950s, but the issue of how they assemble and form is poorly understood," says Sitharam.

Biological viruses are made up of protein molecules that spontaneously come together and spontaneously stop forming to make a spherical, symmetrical entity we know as a virus. The self-assembly process is so quick that researchers have been unable to arrest the process sufficiently in order to study it. Sitharam believes that a focus on three- dimensional geometric relationships will help to shed light on the mystery. "I believe the geometry of these entities plays a key role in obtaining essential snapshots of the process," said Sitharam. "We may not get the entire movie, but we can do a lot with a likely sequence of snapshots."

Utilizing the principle of Geometric Constraints, used commonly in engineering mechanical parts and assemblies, Sitharam has developed algorithms and a software system called FRONTIER Geometric Constraint Solver, where data about a particular virus can be mapped and dumped into the system to produce predicted pathways of how molecules come together to form that particular virus. These predictions are then tested in the wet lab setting to see if they hold true. Thus far, Sitharam and her collaborator, Mavis Agbandje-Mckenna of the Brain Institute, and with a grant from the National Science Foundation, have mapped two viruses, the Murine Parvo Virus, found in mice, and the Maize Streak Virus, which attacks the leaves of corn. A third virus is almost mapped, the Adeno Associated Virus, which is a common human virus. "These particular viruses were chosen because they are of the simplest construction and represent a diversity of basic constructions to test all points of the theory," said Sitharam. Another collaborator, Carl Crane, of Mechanical Engineering will work with Sitharam and McKenna to produce a physical simulation or model of the pathways.

What is the relevance of Sitharam's work? Besides satisfying scientists' insatiable curiosities and the need to know, she feels that if we can understand how viruses form then we can successfully encourage or discourage formation to suit the existing needs of society. She sees applications for arresting infectious diseases and for developments in gene therapy. Will it help with the problem of the cold and AIDS viruses? "Not likely," said Sitharam, "These are extremely complex, ever-changing, stubborn creatures. They continue to evade us. What we could get are some ideas on how to engineer or arrest nanoscale self-assembly."

Sitharam has presented her work at the DARPA NSF BioComputing Conference in Fort Lauderdale and has submitted some of her findings under the title Static Analysis of Viral Assembly Pathways Using Geometric Constraints.

Sitharam joined the faculty of CISE in 1998. She received a B. Tech. from the Indian Institute of Technology, Madras, India, and a Ph.D. in Computer Science in from the University of Wisconsin, Madison. She served as a Humboldt Fellow at the University of Bonn in 1990-1991. She joined the faculty of the Department of Mathematics and Computer Science at Kent State University in 1992. She was a visiting associate professor at Purdue University in 97-98, and visited DIMACS in Spring 98. She feels that UF's CISE Department is heading on a strong path of quality growth toward recognition as one of the top 20 departments in the nation.


Writer: Sandra Braun, sandiw77@bellsouth.net@ufl.edu
Source: Meera Sitharam, 352-392-1260, sitharam@cise.ufl.edu

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