Ours is a joint experimental/theoretical research group devoted to understanding what viruses are and how they "work". We had worked for many years on a wide range of problems involving the statistical physics of complex fluids, e.g., liquid crystals, critical mixtures, surfactant solutions, nanoparticle dispersions, polyelectrolytes, and Langmuir monolayers. But then we learned just enough about viruses to become totally seduced by them.
Like most people, we had known before about the ubiquitous and insidious role of viruses as disease agents. But what we hadn't appreciated is how simple and beautiful they are as physical objects. For example, the picture on the left shows a high-resolution cryo-electron microscopy image of the polio virus. We are looking here at the single-protein-thick shell that protects the viral RNA genome. Each cluster is a 5-mer (see white star) or 6-mer of capsid proteins. These "capsomers" form a two-dimensional hexagonal network with 12 disclination defects (the pentamers) positioned at the vertices of an icosahedron, each surrounded by a ring of 5 hexamers (like the "structure" of a soccer ball, or "Bucky ball" [C60]!). This icosahedral symmetry is a natural consequence of particles aggregating on a sperical surface.
It turns out that thousands of viruses -- ranging from ones that infect bacteria, plants and animals to many that infect humans -- are comparably simple and beautiful. They are uniquely so compared to other "simple" biological objects (e.g., bacteria, yeast and other one-celled organisms), because they are not really alive. For example, viruses have no requirements for food, and no metabolism. They don't "do" anything, but rather are parasites that just diffuse around until they manage to get into a host cell. But they do get replicated, by taking over the biochemical machinery of their host, and hence they evolve like "real" living things.
We are interested in using physical chemical principles to explore generic aspects of viral life cycles. While we necessarily work on only a few, specific, viruses, we try to focus on examples that range over the whole viral kingdom and that provide basic insights into broad classes of viral behavior. For example, we focus on the bacteriophage lambda(λ) as a prototype for the majority of bacterial viruses whose capsids are highly pressurized. They use this pressure to inject their DNA into host cells while their capsids remain outside. Similarly, we work with cowpea chlorotic mottle virus (CCMV) as a typical example of spherical plant viruses that spontaneously self-assemble from their RNA and capsid protein constituents. Finally, the capsids of many animal viruses are enclosed in a bilayer membrane, which they acquire when they "bud out" of a host cell. To understand the budding of such enveloped viruses we are attempting to reconstitute a particular alphavirus (Sindbis) from purified components.
In all cases we design experiments that we believe will elucidate the fundamental aspects of these viral infection cycles - from entry and delivery of the genome, to replication of the virus, to exit from the host cell of a new generation of virions. These problems are investigated in parallel through theoretical formulations of the underlying physical questions involving pressurized bacterial viral capsids, co-self-assembly of RNA and capsid proteins in plant viruses, and the budding behavior of enveloped animal viruses.
Links to projects described above:
- The Origin of Icosahedral Symmetry in Viruses
- Squeezing Viruses with an Atomic Force Microscope
- Packing DNA in Bacteriophages
- Making a Virus in the Laboratory