Jackson Laboratory - An Introduction
For a detailed description of the lab's research, please see the faculty page.
The Jackson Lab is interested in understanding the biology of the simplest human viruses, the picornaviridae. While they are simple and tiny - even for viruses - they cause an astounding amount and variety of human disease. Picornaviruses (the “pico” is for tiny and the “rna” refers to the genetic material) can cause hepatitis, foot-and-mouth disease, poliomyelitis, and the common cold, to name a few diseases.
When a picornavirus moves into a cell, it does so with the goal of turning the cell into a virus factory. Most of the normal functions of a cell are shut down and the cell's resources are diverted to the service of the virus. Most dramatically, the cell's innards are rearranged to the point that they become irreversibly damaged and unrecognizable. The virus uses the rearranged cell membranes to set up "copying centers" where the genetic material of the virus is replicated. Our lab studies the large variety of tricks employed by these viruses to rearrange cell membranes.
For example, poliovirus triggers a "starvation response" so that the cell generates double-membraned structures called autophagosomes. Autophagosomes typically act as recycling centers, gathering up cellular contents and chewing them up so the starving cell has the raw materials to build new proteins. Poliovirus, however, sets up shop right on the surface of these membranes to produce more virus genomes.
We have found that some common cold viruses use this same strategy. However, we also found that one particular common cold virus, Rhinovirus 1A, uses a different trick. It causes the Golgi apparatus, which is used by the cells to sort newly made proteins, to break up into round “vesicles” which provide a base for virus genome factories.
Microscope images of a cell with DNA tagged to glow blue and a protein in the Golgi tagged to glow red. This series shows the result of Rhinovirus infection over time. At 24 hours, the red-tagged round "vesicles" are apparent.
What's surprising is that, to a virologist, poliovirus and Rhinovirus 1A are close cousins, and both need to rearrange cell membranes to produce progeny viruses. However, each does it in a unique way. How do each of their strategies work? Is there some common element among these viruses we could use to target therapeutics and eventually develop a cure for the common cold? These questions currently drive our research.