Tao said her team will use several techniques, including X-ray crystallography and electron cryomicroscopy, to obtain the first three-dimensional structure of the RNA-wrapped NP complex, a structure known as the ribonucleoprotein complex. The group will also purify individual segments of RNA, NP and polymerase; using some painstaking trial-and-error tests, they also will try to decipher the order and arrangements that must be brought together to create a viable ribonucleoprotein.
Krug's group will help determine the function of the various NP structures in replicating the viral RNA segments in cells, as well as how amino acid changes in the NP structure affect the ability of NP to function with the polymerase.
"We want to understand the assembly process," Tao said. "How do all those molecules come together? Obviously it cannot happen all at once. It must take place in a sequential manner, but that process is very poorly understood at the moment."
Krug said the funding for the project -- which comes from the American Recovery and Reinvestment Act -- arrives at a fortuitous time. "The flu is front and center in people's minds right now because of H1N1, and thanks to this grant, we're able to pursue an important new line of research that could answer fundamental questions about the disease."
Source: Rice University