Drop a spec of E. coli bacteria into a cup of sugar water and overnight that clear liquid will transform into a cloudy soup containing a hundred billion (1011) living cells.

This is a movie of E. coli bacteria growing on a microscope slide. Adapted from this this study

Now, into your soup of E. coli bacteria, add a touch of RNA bacteriophage—called “phage” for short—-and in a few hours the cloudy liquid will turn clear again. The once thriving E. coli?…dead. In their place, invisible to the naked eye, are a hundred trillion (1014) new phage.

Here’s a model of phage MS2 generated from X-ray crystallography measurements. Adapted from this study

RNA phage are viruses that infect bacteria. Like other RNA viruses, they’re extreme minimalists, consisting of a protein shell called a “capsid” surrounding an RNA genome encoding a few genes. The phage we work with in our lab, named MS2, is made up of 180 molecules: 178 copies of its coat protein, one copy of its maturation protein, and one copy of its genomic RNA. That’s it! Armed only with these two-hundred-or-so molecules, viruses like MS2 are able to infect their hosts, highjack the host cells’ machinery, and replicate in tremendous yield.

This is a cartoon of an RNA virus infecting a host cell

Because they’re made from so few molecules, RNA viruses can be studied and understood “from the bottom up” using physical chemistry. In our lab, we take the viruses apart, we separate their protein and RNA, and then we put them back together. We measure the structure and dynamics of the viral molecules in isolation, and then we measure collective properties that emerge when the molecules interact with eachother. We team up with theorists and computational chemists to turn our measurements into quantitative models that help us understand how viruses perform complex biological functions, like infection.

Here’s our best guess at the folded structure of MS2’s RNA. Each dot is a nucleotide, and about half of them are paired with other nucleotides to form a complex and biologically important pattern. Adapted from this study

We are especially fascinated by the process of “self-assembly”, which is when an ordered structure appears spontaneously from an initially disordered mixture of molecules. RNA viruses are experts in self-assembly—it’s how they build their protein capsids and fold their RNA genomes—and one cannot fully appreciate or understand how these viruses operate without understanding how they self-assemble. Our lab uses ultra sensitive optical microscopes and tools from a field called “DNA nanotechnology” to measure viral self-assembly at small length scales (nanometers) and over a broad range of time scales (milliseconds to days).

Our lab measures the size of individual self-assembling viruses using laser interferometry. See this study and this study
Our lab maps the structure of viral RNA by measuring how it binds to many short DNA strands. See this study

In addition to teaching us about how viruses work, we hope our results will inspire new ways of repurposing viruses to do useful things, such as delivering therapeutic cargos to cells. And we also hope to uncover new ways to block the spread of harmful viruses that cause disease.