个人简介

Ph.D., Lund University

研究领域

Biophysical

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.

近期论文

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U. Sae-Ueng, T. Liu, C. E. Catalano, J. B. Huffman, F. L. Homa, A. Evilevitch, "Major capsid reinforcement by a minor protein in herpesviruses and phage". Nucleic Acids Research 2014, Jul 22. pii: gku634. U. Sae-Ueng, D. Li, X. Zuo, J.B. Huffman, F.L. Homa, A. Evilevitch, "Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection". Nature Chemical Biology, 2014. 07 September 2014; doi:10.1038/nchembio.1628 T. Liu, U. Sae-Ueng, D. Li, G. Lander, X. Zuo, B. Jönsson, D. Rau, I. Shefer, A. Evilevitch, "Solid-to-fluid-like DNA transition in viruses facilitates infection". PNAS 2014; published ahead of print September 30, 2014, doi: 10.1073/pnas.1321637111 David Bauer, Jamie Huffman, Fred Homa, Alex Evilevitch, "Herpes Virus Genome, The Pressure is On", Journal of the American Chemical Society, July 5, 2013, 135 (30), pp 11216-11221; doi: 10.1021/ja404008r A. Evilevitch, "Physical evolution of pressure-driven viral infection", New and Notable Article, Biophysical Journal, Volume 104, Issue 10, 2113-2114, 21 May 2013; doi 10.1016/j.bpj.2013.03.062 G. C. Lander, J. E. Johnson, D. C. Rau, C. S. Potter, B. Carragher, A. Evilevitch, “DNA bending induced phase transition of encapsidated genome in phage lambda”, Nucleic Acids Research, 28 February 2013; doi 10.1093/nar/gkt137 Aylin Ahadi, Dan Johansson, A. Evilevitch, “Modeling and simulation of the mechanical response from nanoindentation test of DNA-filled viral capsids ”, Journal of Biological Physics, March 2013; doi 10.1007/s10867-013-9297-9 Emrecan Soylemez, Maarten P. de Boer, Udom Sae-Ueng, Alex Evilevitch, Tom A. Stewart, May Nyman, "Photocatalytic Degradation of Bacteriophages Evidenced by Atomic Force Microscopy", PLoS One, January 3, 2013, Vol. 8, Issue 1, e53601. Elmar Nurmemmedov, Martin Castelnovo, Elisabeth Medina, Carlos E Catalano, Alex Evilevitch, "Challenging packaging limits and infectivity of phage lambda", Journal of Molecular Biology,13 January 2012, Vol. 415, Issue 2, pp 263-273 . Pernilla Nevsten, Alex Evilevitch, and Reine Wallenberg, “Chemical mapping of DNA and counter-ion content inside phage by energy-filtered TEM”, Journal of Biological Physics, March 2012, Vol. 38, Issue 2, pp 229-240. A. Evilevitch, W. H. Roos, I. L. Ivanvoska, M. Jeembaeva, B. Jönsson, and G. J. L. Wuite, “Effects of Salts on Internal DNA Pressure and Mechnical Properties of Phage Capsids”, Journal of Molecular Biology, Vol. 405, Issue 1, 2011. M. Jeembaeva, B. Jönsson, M. Castelnovo, and A. Evilevitch, “DNA Heats Up: Energetics of Genome Ejection from Phage Revealed by Isothermal Titration Calorimetry”, Journal of Molecular Biology, Vol. 395, Issue 5, 2010. S. Koester, A. Evilevitch, M. Jeembaeva, and D. Weitz, “Dependence of Capsid-Pressure Dependence on Viral Infection by Phage Lambda”, Biophysical Journal, Vol. 97, Issue 6, 2009. A. Ahadi, J. Colomo, A. Evilevitch “Simulation of Nanoindentation Response of Viral Capsids. Shape and Size Effects”, ”, J. of Phys. Chem. B, Mar 19;113(11):3370-8, 2009. G. Lander, A. Evilevitch, M. Jeembaeva, C. S. Potter, B. Carragher, 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, A. Evilevitch “Osmotic pressure: inhibiting or promoting DNA ejection from phage”, J. Mol. Biol. Aug 29;381(2):310-23, 2008. Epub 2008 June 6. A. Evilevitch, L. Fang, A. Yoffe, M. Castelnovo, D. C. Rau, V. A. Parsegian, W. M. Gelbart, C. M. Knobler “Effects of salt concentrations and bending energy on the extent of ejection of phage genomes”, Biophysical Journal, Feb, Vol. 94 1110-1120, 2008. E. Nurmemmedov, M. Castelnovo, C.E. Catalano, A. Evilevitch "Biophysics of viral infectivity: matching genome length with capsid size." Q Rev Biophys. 2007 Nov;40(4):327-56. Review. M. Castelnovo and A. Evilevitch, “DNA ejection from bacteriophage: towards a general behavior for osmotic suppression experiments” Eur. Phys. J. E 24, 9-18, 2007. D. Löf, K. Schillén, B. Jönsson, A. Evilevitch “Dynamic and static light scattering of DNA ejection kinetics from phage” Physical Review E, Vol. 76, No 1, 011914, 2007.