Gustavo Monteiro Silva: From Brazil, Taking on a Crucial Challenge in Cell Biology

Part of the Introducing the New Faculty, 2017 Series
Gustavo Monteiro Silva
Gustavo Monteiro Silva is launching new studies of a key process of how a cell "cleans house." Photo by Duke Photography

With his tortoise shell aviator glasses and tight ringlets of hair shaped straight up in a fade, Gustavo Monteiro Silva looks a bit younger and hipper than one might expect of a newly hired assistant professor of biology at Duke.

And that’s a good thing, Silva says. “We need to make science more diverse and inclusive. Students need to see role models. They need to see a reflection of themselves.”

Brazilian-born and educated Silva, 35, is indeed a strong example. After a lucky break that moved him into a more enriched private high school in São Paulo alongside well-off white kids who spoke English, drove their own cars and took European vacations, he was able to study hard and put himself on the path to college. “None of this could have happened without my mother’s support, who sacrificed everything so I could have a better education,” he said.

As an undergraduate at the University of São Paulo he joined Luis Netto’s lab that was studying the process by which the cell ‘cleans house’ and recycles proteins it doesn’t want or need, and then stayed on for his Ph.D. to investigate it further.

Though he always thought the know-it-all scientists he saw on TV were cool, the turning point that truly brought Silva into fully considering a career in science was an encounter with Jamaine Davis of the Meharry Medical College in Nashville, who visited his Brazilian campus. “I had never seen a black scientist before!” Silva says.

After the encounter, he maintained a long-distance correspondence with Davis, who apart from everybody else mentored him beyond science, “including lessons on the challenges of being a black scientist in a mostly white environment.”

Davis helped Silva land a postdoctoral position under systems biologist Christine Vogel at NYU, which lasted six years. “She took a risk with me. I did not have international experience, nor any reference letters from big shots and I came in with a project in mind. I believe it paid off.”

At NYU, Silva started his work on ubiquitin, a protein which had been named for its ubiquitous appearance in the cells of many different kinds of organisms. It remains remarkably similar across different phyla, meaning it plays a crucial role in cell biology.

Although ubiquitin is most known for being the molecular flag that marks a damaged or un-needed protein for collection and disposal by the proteasome, the ubiquitous signaling protein also turns out to have many other jobs. Silva recently discovered that ubiquitin can regulate the manufacturing of proteins, which is a fundamental process in response to cellular stress, and that’s where he wants to take his science at Duke.

“Ubiquitin has a lot of other functions. A lot. A lot! And we need to solve this puzzle to increase cellular resistance to harmful conditions and to treat stress-related diseases such as Parkinson’s and Alzheimer’s,” he says in his still-unadorned office on the third floor of the French Family Science Center. A corner of his desk holds a stack of catalogs from lab equipment manufacturers because the salespeople tend to descend on a new hire, he says with a laugh.

To explain ubiquitin’s versatility, Silva uses an analogy to Lego blocks. Even though each unit of the protein is essentially the same, they can be linked up in chains of various shapes and sizes, depending on how each unit attaches to the previous one. And those assembled shapes convey many different meanings to the cell’s machinery, from controlling protein synthesis to moving proteins around, to promoting protein degradation or interactions with other proteins.

Silva is in awe of the number of mammalian enzymes devoted to ubiquitin signaling – up to 1,000, some researchers estimate – which would be as much as 5 percent of our genome. “Having this many genes devoted to the ubiquitin system reflects the importance of the system,” he says. “Dysfunction of ubiquitin enzymes is linked to a variety of human diseases.”

As with cell division and other intricate biological mechanisms, the complexity of the ubiquitin signaling system gives it better calibration and responsiveness, Silva says. Like an expensive wristwatch, more moving parts can mean more precision in regulation.

He’s excited to see what’s hidden in all that complexity and where it might lead. “Playing with protein dynamics in the field of proteomics is an interesting way to discover and develop new therapies for many diseases,” he says. 

But as compelling as his research is, Silva says he won’t lose sight of his responsibility to Duke students, especially the ones like him who might have been viewed as a long-shot.

“If you have the opportunity, fair treatment, and resources, then you can make it work,” he says. “The racial disparity seen today is not a matter of intellectual capacity, and once I was in that private high school, it was just a matter of studying hard. I tell my students there are very few true geniuses out there.”