Alex Evilevitch-The Center for Nucleic Acids Science and Technology - Carnegie Mellon University

Alex Evilevitch

Associate Professor of Physics

Phone: (412) 268-2748

Research

The majority of viruses possess spherical, icosahedral protein shells with radii varying between 10 nm and 100 nm and with thicknesses of a few nanometers corresponding to single protein layer. Viral capsids protect genomes that are tens of microns in contour length. Sufficient genome encapsidation implies that the virus must be stable enough to withstand internal forces exerted by its packaged genome and external forces from its environment. Yet, it must be unstable enough to rapidly release its genome in the cell during infection. Thus, there must exist a unique match between the virus' genome length, capsid size and strength that is adjusted to the biological and physical properties of the host cell. Internal genome pressure, reaching tens of atmospheres as a result of strong confinement, is required for phages and many other dsDNA viruses to be able to infect by passive ejection of its genome. Besides from determining this pressure, we also found that it provides additional support to the strength of the viral capsid helping the virus survive external deformations imposed on it between infections.

The Evilevitch group uses biophysical approaches in order to learn about the fundamental physical principles that control viral genome encapsidation and release as well as capsid stability. This research program takes advantage of the high resolution cryo electron microscopy, AFM, light scattering and microcalorimetry. Furthermore, our findings provide tools for the rational design of therapeutic agents that selectively interfere with the encapsidation process, and in addition, tools to improve encapsidation in vitro in order to make stable vectors for gene delivery.

Publications

A. Evilevitch, Physical evolution of pressure-driven viral infection. New and Notable Article, Biophysical Journal 2013, accepted

Ahadi, Aylin; Johansson, Dan; Evilevitch, A. Modeling and simulation of the mechanical response from nanoindentation test of DNA-filled viral capsids.. Journal of Biological Physics 2013; doi 10.1007/s10867-013-9297-9

Lander, G. C.; Johnson, J. E.; Rau, D. C.; Potter, C. S.; Carragher, B.; Evilevitch, A. DNA bending induced phase transition of encapsidated genome in phage lambda. Nucleic Acids Research 2013; doi 10.1093/nar/gkt137

Soylemez, Emrecan; de Boer, Maarten P.; Sae-Ueng, Udom; Evilevitch, Alex; Stewart, Tom A.; Nyman, May Photocatalytic Degradation of Bacteriophages Evidenced by Atomic Force Microscopy. PLoS One 2013, Vol. 8, Issue 1, e53601.

Nevsten, Pernilla; Evilevitch, Alex; Wallenberg Reine Chemical mapping of DNA and counter-ion content inside phage by energy-filtered TEM. Journal of Biological Physics 2012, Vol. 38, Issue 2, pp 229-240.

Nurmemmedov, Elmar; Castelnovo, Martin; Medina, Elisabeth; Catalano, Carlos E., Evilevitch, Alex Challenging packaging limits and infectivity of phage lambda. Journal of Molecular Biology 2012, Vol. 415, Issue 2, pp 263-273 .

Evilevitch, A.; Roos, W. H.; Ivanvoska, I. L.; Jeembaeva, M.; Jönsson, B.; Wuite, G. J. L. Effects of Salts on Internal DNA Pressure and Mechnical Properties of Phage Capsids. Journal of Molecular Biology 2011, Vol. 405, Issue 1.

Jeembaeva, M.; Jönsson, B.; Castelnovo, M.; Evilevitch, A. DNA Heats Up: Energetics of Genome Ejection from Phage Revealed by Isothermal Titration Calorimetry. Journal of Molecular Biology 2010, Vol. 395, Issue 5.

Ahadi, A.; Colomo, J.; Evilevitch, A. Simulation of Nanoindentation Response of Viral Capsids. Shape and Size Effects. J. of Phys. Chem. B 2009, 113(11):3370-8.

Koester, S.; Evilevitch, A.; Jeembaeva, M.; Weitz, D. Dependence of Capsid-Pressure Dependence on Viral Infection by Phage Lambda. Biophysical Journal 2009, Vol. 97, Issue 6.