Alex Evilevitch

Associate Professor, Physics

Education

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.

Our 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.

Selected Publications

• M. Jeembaeva, B. Jonsson, M. Castelnovo, and A. Evilevitch, DNA Heats Up: Energetics of Genome Ejection from Phage Revealed by Isothermal Titration Calorimetry, J. Mol. Biol. 395, Issue 5 (2010).
• S. Koester, A. Evilevitch, M. Jeembaeva, and D. Weitz, Dependence of Capsid-Pressure Dependence on Viral Infection by Phage Lambda, accepted, Biophys. J. 97, Issue 6 (2009).
• A. Ahadi, J. Colomo and A. Evilevitch, Three-Dimensional Simulation of Nanoindentation Response of Viral Capsids: Shape and Size Effects, J. of Phys. Chem. B 19, 3370-3378 (2009).
• G. C. Lander, A. Evilevitch, M. Jeembaeva, C. S. Potter, B. Carragher, and J. E. Johnson, Bacteriophage Lambda Stabilization by Auxiliary Protein gpD: Timing, Location, and Mechanism of Attachment Determined by Cryo-EM, Structure 16, 1399-1406 (2008).
• M. Jeembaeva, M. Castelnovo, F. Larsson, and A. Evilevitch, Osmotic Pressure: Resisting or Promoting DNA Ejection from Phage? J. Mol. Biol. 381, 310-323 (2008).
• A. Evilevitch, L. T. Fang, A. M. Yoffe, M. Castelnovo, D. C. Rau, V. A. Parsegian, W. M. Gelbart, and C. M. Knobler, Effects of Salt Concentrations and Bending Energy on the Extent of Ejection of Phage Genomes, Biophys. J. 94, 1110-1120 (2008).
• E. Nurmemmedov, M. Castelnovo, C. E. Catalano, and A. Evilevitch, Biophysics of Viral Infectivity: Matching Genome Length with Capsid Size, Q. Rev. Biophys. 40, 327-356 (2007).
• M. Castelnovo and A. Evilevitch, DNA Ejection from Bacteriophage: Towards a General Behavior for Osmotic Suppression Experiments, Eur. Phys. J. E24, 9-18 (2007).
• D. Löf, K. Schillén, B. Jönsson, and A. Evilevitch, Dynamic and Static Light Scattering of DNA Ejection Kinetics from Phage, Phys. Rev. E 76, 011914 (2007).
• I. Ivanovska, B. Jönsson, G. Wuite, and A. Evilevitch, Internal DNA Pressure Modifies Stability of Wild-Type Phage, PNAS 104, 9603-8 (2007).
• D. Löf, K. Schillén, B. Jönsson, and A. Evilevitch, Forces Controlling the Rate of DNA Ejection from Phage Lambda, J. Mol. Biol. 368, 55-65 (2007).
• A. Evilevitch, Effects of Condensing Agent and Nuclease on the Extent of Ejection from Phage Lambda, J. Phys. Chem. B 110, 22261-22265 (2006).
• M. Castelnovo and A. Evilevitch, Binding Effects in Multivalent Gibbs-Donnan Equilibrium, Europhys. Lett. 4, 73 (2006).
• P. Grayson, A. Evilevitch, M. M. Inamdar, P. K. Purohit, W. M. Gelbart, C. M. Knobler, and R. Phillips, The Effect of Genome Length on Ejection Forces in Bacteriophage Lambda, Virology 348, 430-436 (2006).
• A. Evilevitch, J. W. Gober, M. Phillips, C. M. Knobler, and W. M. Gelbart, Measurements of DNA Lengths Remaining in a Viral Capsid after Osmotically Suppressed Partial Ejection, Biophys. J. 88, 751-756 (2005).
• A. Evilevitch, M. Castelnovo, C. M. Knobler, and W. M. Gelbart, Measuring the Force Ejecting DNA from Phage, J. Phys. Chem. B 108, 6838-6843 (2004).
• A. Evilevitch, L. Lavelle, E. Raspaud, C. M. Knobler, and W. M. Gelbart, Osmotic Pressure Inhibition of DNA Ejection from Phage, PNAS 100, 9292-9295 (2003).