02 February 2006
A new look at intra-cellular viral activity
The hepatitis C virus has found a clever way to hijack the body's cells and even make an end-run around defenses that cells throw up to stop its spread, according to new research by Berkeley scientists.
While revealing the inventiveness of viruses, the finding also is leading the researchers to probe ever-finer details of the process so they eventually can develop drugs to prevent the virus from taking over and establishing an infection.
"The goal of this work is to get enough detail on the mechanisms involved to design a drug to prevent the disease," said biochemist Jennifer Doudna, professor of chemistry and of molecular and cell biology. Biophysicist Eva Nogales, associate professor of molecular and cell biology, added: "This is basic research, telling us how hepatitis C acts. The more we learn about how it does things, the easier it will be to block it without interfering otherwise with the normal mechanism of the cell."
Scientists have known that the blood-borne virus hepatitis C and numerous other viruses - including the flu virus, polio, hepatitis A, and the human immunodeficiency virus (HIV) - take over the machinery inside the cell that produces proteins and use it to make copies of themselves. Specifically, these viruses hijack the ribosome, a huge molecular complex that manufactures proteins based on a blueprint called messenger RNA (mRNA). The viruses not only force the ribosomes to manufacture viral proteins, they also suppress production of the cell's own proteins.
Moreover, hepatitis C does this in a way that circumvents the normal protein-production process, so that even when the cell tries to shut down protein manufacturing by the ribosomes to fight the virus, the virus is able to hot-wire the ribosomes.
Doudna, Nogales, and their colleagues found out how this happens by using a technique, perfected by Nogales, called cryo-electron microscopy (cryo-EM), to provide detailed pictures of the RNA and protein complexes involved. Cryo-electron microscopy allows researchers to get images of large molecules in a liquid environment like that inside the cell - in contrast with X-ray crystallography, where it is necessary to make a molecule condense into a hard crystal before it can be imaged.
"Cryo-EM is good because we don't have to crystallize the molecule, so we can deal with conformational flexibility, which is very important," Nogales said. "All these protein machines have moving parts. Because we don't have to crystallize our complexes, which really paralyzes them, we are able, with some ingenuity, to detect and describe the flex inherent to the complexes of the components. It is looking at complexes as they are in the cell."
- Robert Sanders
Perception may indeed be filtered - in part - through language
The language we speak affects half of what we see, according to researchers from Berkeley and the University of Chicago.
Scholars have long debated whether our native language affects how we perceive reality - and whether speakers of different languages might thus see the world differently. The idea that language affects perception is controversial, and results have conflicted.
A paper published this month in the journal Proceedings of the National Academy of Sciences supports the idea - but with a twist. The paper suggests for the first time that language affects perception in the right half of the visual field, but much less, if at all, in the left half.
The paper was written by Aubrey Gilbert, Richard Ivry, and Paul Kay at Berkeley and Terry Regier at the University of Chicago.
This new finding is suggested by the organization of the brain, the researchers say. Language function is processed predominantly in the left hemisphere of the brain, which receives visual information directly from the right visual field. "So it would make sense for the language processes of the left hemisphere to influence perception more in the right half of the visual field than in the left half," says Chicago's Regier, an associate professor of psychology who proposed the idea behind the study.
The team confirmed the hypothesis through experiments designed and conducted in psychology professor Ivry's lab at Berkeley. The experiments tested Berkeley undergraduates and also a patient whose brain hemispheres had been surgically separated.
Many of the distinctions made in English, such as between colors, do not appear in other languages, and vice versa, according to researchers. Earlier studies addressing the possible influence of language on perception tended to look for a simple "yes" or "no" answer: Either language affects perception, or it does not. In contrast, the current findings support both views at once. Language appears to sharpen visual distinctions in the right visual field, and not in the left. In their paper, the researchers conclude that our representation of the visual world "may be, at one and the same time, filtered and not filtered through the categories of language."