Dr. Silva studies how cells respond to stress using a systems biology approach - his work generates and looks for patterns in large-scale datasets to try to understand all the different roles that a stress response factor can play.

A native of Brazil, Dr. Silva earned both his undergraduate and graduate degrees from the University of Sao Paulo. He completed postdoctoral work at the Center for Genomics and Systems Biology at New York University.

It has been known since the 1970s that cells often flag proteins for degradation by attaching a small protein called ubiquitin. (It was named for how ubiquitous it was in every sample looked at.) However, since then, more and more functions for ubiquitin have been reported and these different functions have been associated with structural differences. Specifically, proteins are often flagged with chains of ubiquitin and the biochemistry of how these ubiquitin molecules attach to each other is thought to define different “flag” types.

In a recent paper, Dr. Silva looked at the K63 ubiquitin chain in yeast. (It’s called K63 because in this type of chain, the ubiquitin molecules attach to one another at lysine 63.) To get an unbiased list of all of the proteins tagged with K63 ubiquitin chains, he extracted all of the proteins from yeast cells and then “enriched” the sample for proteins attached to K63 ubiquitin using a protein bait. (You can think of this like a magnet that will attract mostly the proteins you want and leave everything else behind.) Finally, he used a method called mass spectrometry to identify what the isolated proteins were.

Dr. Silva was able to compare the results from this method between yeast that were growing happily and yeast that were stressed by the addition of hydrogen peroxide. Out of the 490 proteins that changed significantly in response to stress, 37 were part of the ribosome, the cellular factory that produces proteins from RNA. This makes some sense because under stress conditions, the ribosome takes longer to produce proteins.

Following up on that, he found that binding of K63 ubiquitin to ribosome components reduced the association of factors that help the ribosome elongate the emerging protein. However, he was not able to conclude whether it was blocking these factors from binding to the ribosome or making their interactions less stable.

In addition to these interesting results, this study was also the first time that this particular strategy was used to study all of the proteins associated with a certain variety of ubiquitin simultaneously. Demonstrating that this approach works is another valuable contribution to the field.