Biophysics Lecture

Viruses are dreaded disease agents and consummately evolving organisms whose structural, genetic, cellular, and immunological aspects have long been investigated by biologists and medical researchers. But viruses are also simple, inanimate, objects whose physical properties outside the cell can be fruitfully addressed by a wide range of theoretical and experimental approaches. In particular, we have found it useful to understand differences in the life cycles of RNA and DNA viruses in terms of the differences between RNA and DNA as physical objects. RNA, for example, is a significantly more compact and flexible molecule than DNA containing the same amount of genetic information. Accordingly, many RNA viruses are assembled spontaneously by interaction of their RNA genome with its capsid proteins, whereas genome packaging in most DNA viruses requires a great deal of work to be done and necessarily involves the build-up of a high pressure in the capsid. In this talk I discuss our calculations and measurements of the self-assembly of RNA viruses from purified components and of the pressures and forces in DNA viruses. I feature the role of statistical mechanical principles in developing the basic theory of these phenomena, and of the application of experimental techniques such as synchrotron small-angle X-ray scattering (SAXS), fluorescence correlation spectroscopy (FCS), and cryo-electron microscopy (cryo-EM). Finally, I discuss our ongoing efforts (begun at Caltech almost 7 years ago) to reconstitute an infectious enveloped virus outside the cell, and to similarly synthesize from scratch various hybrid virus-like particles using a mix of components purified from plant and animal viruses.