Biophysics of viruses

• Alex Evilevitch

POST-DOC POSITION IN VIRUS BIOPHYSICS IS AVAILABLE!

Viruses are among the simplest biological objects. They typically consist of a container, called a capsid, which holds the viral genome. Viral genome is a long, charged molecule enclosed in a rigid protein shell of the capsid. This physical situation implies that the genome is highly stressed.
My group wants to understand as broadly as possible the common physical features controlling the life cycle of viruses, building the program on a broad range of in vitro experiments with phage and plant virus systems. The research is of interest both to biologists and physical scientists. It involves a physical-chemical approach to understand as broadly as possible the state of stress of a long, semi-flexible, chain, whose length is hundreds of times larger than the dimension of the volume of the viral capsid. The study specifically involves determination of the: mechanism for packaging/ejection of viral genome; pressures involved; the strengths of the capsids; limits of the amount of material that can be encapsidated. Moreover, a more applied part of this research involves a study of the controlled self-assembly of viral nanocontainers with and without cargo molecules.
The experiments build on our recently discovered way to determine pressure inside viruses. In this way, we estimated that lambda phage virus's internal pressure is greater than 40 atmospheres!
The main tools we are using are: high-resolution cryo electron microscopy with tomography and single particle reconstruction to determine genome structure/arrangement under various packaging conditions of physiological interest; microcalorimetry for direct measurements of the energies associated with interactions between genome and capsid; light scattering for kinetic studies of genome release; and atomic force microscopy to study mechanical properties of viral capsids. Experimental design and interpretation of results is made in close connection with the biophysical modeling performed in the group.
To summarize, this work is intended to provide a general mechanism of viral infection. It also suggests a possible strategy for redesigning viruses as drug-delivery agents.
The work is mainly supported by the Swedish Research Council (VR), Lawskis Foundation, Carl Tryggers Foundation, Crafoord Foundation and Royal Physiographic Society in Lund.

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