The Physical Virology Group

Carnegie Mellon University, Department of Physics
Principle Investigator: Prof. Alex Evilevitch

http://www.cmu.edu/physics/index.html
 

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Physical Virology of Herpesviruses and Phage

Viruses are simple lifeless entities that cannot reproduce on their own and therefore depend on host cells to provide them with the necessary life support mechanisms. Simplified, all viruses consist of a protein shell (capsid) that protects the viral genome (DNA or RNA). To infect, the viral genome must enter the cell, where it hijacks the host cell’s machinery and synthesizes multiple copies of virions. This can lead to cell lysis, which is a lethal event.

Physical virology is a rather new field that seeks to define the physical mechanisms controlling virus development. This knowledge can provide information essential to the rational design of new anti viral strategies with less specificity for a limited number of viruses. Furthermore, biological and physical simplicity relative to other biological systems have made viruses an attractive physical model system to study fundamental prosperities of DNA compaction and translocation as well as protein self-assembly using viral capsids.

Research Interests

Evilevitch's physical virology group investigates fundamental physical principles that control viral encapsidation and genome release. Our group has discovered a way to determine genome pressure in viral capsid and found that to be as high as 40 atm in bacteriophage lambda, a pressure equivalent to that at a depth of 1200 ft in the ocean. We are specifically interested in determining the physical nature of genome packaging, the kinds of pressures involved, the strengths and elastic properties of the capsids, and limits on the amount of material that can be encapsidated. The main tools in the lab are: Atomic Force Microscopy (AFM), microcalorimetry, and high resolution cryo electron microscopy.

*Cryo-EM: 3D Cryo-electron microscopy reconstructions of DNA-filled and empty phage capsid.
* AFM: Atomic Force Microscopy high-resolution imaging of page capsids and breaking the phage with an AFM cantilever.
* ITC: Isothermal Titration Calorimetry setup showing the titration of phage solution (from the syringe) into the LamB receptor solution in the sample cell.