Slavov Receives NIH Director’s New Innovator Award

Direct evi­dence. It’s the holy grail in sci­en­tific discovery.

Nikolai Slavov, assis­tant pro­fessor in the Depart­ment of Bio­engi­neering, found that grail in the least likely of places: deep inside ribo­somes, the mol­e­c­ular machines in cells that assemble all the pro­teins that keep living things—from bud­ding yeast to us—functioning.

This month, the National Insti­tutes of Health rec­og­nized Slavov’s ground­breaking research with its Director’s New Inno­vator Award. The five-​​year, $2.35 mil­lion award is part of the NIH Common Fund’s High-​​Risk, High-​​Reward Research pro­gram, which sup­ports highly cre­ative early-​​career researchers taking out-​​of-​​the-​​box approaches to major chal­lenges in bio­med­ical research.

Slavov’s work flew in the face of sci­en­tists’ decades-​​long assump­tion that all ribo­somes were the same. Some spec­u­lated that their com­po­si­tion, and hence their func­tion, might vary, but no one had been able to pro­vide exper­i­mental or obser­va­tional proof of the claim.

Ribo­somes are one of the most fun­da­mental and highly con­served struc­tures in biology. Our work could help reshape our under­standing of a cen­tral tenet of the field: how infor­ma­tion from genes is reg­u­lated.
—Nikolai Slavov, assis­tant professor

Until, that is, Slavov and his col­leagues revealed the dis­par­i­ties in full-​​color schematics last year in a paper pub­lished in the journal Cell Reports. The con­cept of “spe­cial­ized ribosomes”—that not all ribo­somes house the same stan­dard 80 core pro­teins but rather vari­eties of them—had finally been val­i­dated. The find­ings could have impli­ca­tions for new direc­tions in fields from cancer ther­a­peu­tics to regen­er­a­tive medicine.

“Ribo­somes are one of the most fun­da­mental and highly con­served struc­tures in biology,” says Slavov. “The grant will enable me to inves­ti­gate the spe­cial­ized ribo­some hypoth­esis fur­ther and flush out how the ribo­somes’ varying com­po­si­tions affect their bio­log­ical func­tion. Our work could help reshape our under­standing of a cen­tral tenet of the field: how infor­ma­tion from genes is regulated.”

Upending con­ven­tional wisdom

Before Slavov’s dis­covery, sci­en­tists believed that ribo­somes in unper­turbed cells had a pas­sive role in the expres­sion of genetic infor­ma­tion. A mol­e­cule called mes­senger RNA, or mRNA, picked up protein-​​assembly instructions—which amino acids to link in a chain and in what order they should link—from genes and deliv­ered them to the ribo­some to follow.

Slavov’s find­ings, how­ever, indi­cated that ribo­somes not only assem­bled pro­teins, they also appeared to reg­u­late that pro­duc­tion. In a sense, a fac­tory line worker had now become a plant foreman. Ribo­somes may deter­mine, for example, how many and which types of pro­teins will be made in spe­cific tissues.

The poten­tial appli­ca­tions are broad. In tissue engi­neering, for example, if researchers want to pro­gram, say, an embry­onic stem cell to make a heart cell, they may now have to take into account how to influ­ence the ribo­some. If a genetic muta­tion has led to a core-​​protein mal­func­tion that con­tributes to the growth of cancer, researchers may now con­sider devel­oping drugs that target that ribo­somal core pro­tein to restore its func­tion, inhibiting cancer growth.

“The award sup­ports basic research—those appli­ca­tions are in the future,” says Slavov. “But con­tinued val­i­da­tion of my spe­cial­ized ribo­somes hypoth­esis could one day directly sug­gest rational ther­a­pies for can­cers such as glioblas­toma, which cur­rently doesn’t have any effec­tive treatment.”

‘Northeastern’s spirit of boldness’

To dive into the inner-​​workings of the ribo­some, Slavov used the most sophis­ti­cated mass-​​spectrometry tech­niques to ana­lyze the core pro­teins in ribo­somes from both bud­ding yeast cells and mouse embry­onic stem cells. Exploring such dis­sim­ilar cell types per­mitted him to gen­er­alize his results.

There is this momentum and enthu­siasm for taking smart risks among both the fac­ulty and stu­dents at Northeastern—asking big ques­tions and doing what­ever is required to con­tribute to their res­o­lu­tion.
—Nikolai Slavov, assis­tant professor

With the award from the NIH, Slavov will con­tinue honing his tools of the trade, inventing low-​​cost, high-​​throughput ways to directly mea­sure ribo­somes’ rate of pro­tein syn­thesis and accu­rately quan­tify and dis­tin­guish their core pro­teins from one another, regard­less of how sim­ilar those pro­teins may appear.

As the award attests, Slavov has come a long way in his short time at North­eastern. He joined the fac­ulty last fall and now has three grad­uate stu­dents and five under­grad­u­ates in his lab accom­pa­nying him on his journey inside the cell’s remark­able protein-​​synthesizing machinery. He credits the university’s entre­pre­neurial vision as instru­mental in his rapid progress.

“The university’s spirit of bold­ness is very much aligned with this award,” he says. “There is this momentum and enthu­siasm for taking smart risks among both the fac­ulty and stu­dents at Northeastern—asking big ques­tions and doing what­ever is required to con­tribute to their resolution.”