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As a McGill University undergraduate, Andrew Emili earned money putting together IKEA furniture. The assembly instructions may have stymied his customers, but at least instructions existed. That’s more than can be said for Emili’s current challenge: mapping the network of interactions between the tens of thousands of proteins encoded in the human genome.
“It’s like trying to put together IKEA furniture when you’ve lost the assembly instructions,” says Emili, a molecular systems biologist who arrived at Boston University from the University of Toronto in July. “You see bolts, you see holes, and you know the relationship between the two, but not which ones go where.”
Emili, jointly appointed to the School of Medicine biochemistry department and the College of Arts & Sciences biology department, is director of the new University-wide Center for Network Systems Biology (CNSB).
Human health and development depend on the network of protein interactions, he says. Yet despite rapid advances in genomics, scientists know little about how these interactions work and how faulty interactions lead to disease. He uses proteomics, the study of the protein products of genes, and mass spectrometry, a tool that can separate individual proteins from their connections, as well as bioinformatics and other molecular genetic and genomic technologies, to create maps of protein interactions. He then makes his maps, which he describes as assembly instructions for molecular networks, available to the broader research community. His ultimate goal, he says, is to translate this basic knowledge into novel diagnostic and therapeutic tools for cancer, cardiovascular disease, and Alzheimer’s disease and other neurodegenerative disorders.
Emili’s vision for the CNSB, he says, is “to create a highly collaborative, multidisciplinary research hub that tackles important fundamental questions in the field by forging new links with interested researchers across both BU campuses, the greater Boston area, and the world.”
Emili is widely regarded as a leader in proteomics, mass spectrometry, and network systems biology, says David Harris, a MED professor and chair of biochemistry. He says Emili’s work with mass spectrometry will complement that of Catherine E. Costello, a William Fairfield Warren Distinguished Professor, a MED professor of biochemistry, and director of the Center for Biomedical Mass Spectrometry. With Emili’s arrival, Harris says, “we have an incredibly strong presence in multiple kinds of mass spectrometry.”
While the CNSB, as well as Emili’s lab, will be housed within the biochemistry department, he will serve as a bridge between the Medical and Charles River Campuses and will also have an office in the Life Science & Engineering Building—and eventually some lab space—at 24 Cummington Mall and teach classes in the biology department.
“He will collaborate widely across the University,” says Harris. “This recruitment from the start was a joint effort of the medical school and the Charles River Campus.”
“It’s really great to have him come in and be a leader,” says Kim McCall, a CAS professor and chair of biology, noting that her department has recently hired three junior faculty in systems biology. “His research is highly collaborative. He’s already talking to people in chemistry. He’s done work related to evolution, so that bridges with our scientists who are doing evolutionary biology. He’ll be important to bioinformatics on the CRC as well.”
“If you really want to understand the cell,” Emili says, “you have to understand what the protein molecules do—how they interact, what their functions are, how they’re regulated. The DNA is the code or the raw information, but the proteins are the molecules that are the building blocks. They’re not just abstract information. You can think of them as the construction workers in the cell.”
He thinks of his team of researchers, he says, “as a Google or Facebook of biology,” mapping social networks of proteins that provide clues to how proteins function. “Proteins interact functionally and physically in very dynamic and intriguing ways,” he says. “It’s about who knows who and who’s connected to whom.
“In a disease state, these networks are often perturbed or modified or they fail in some way,” he says, “and if we want to reverse a disease or prevent it, we have to understand how the networks go awry and what something looks like when it’s broken and what it looks like when it’s not broken.”
In 2015, Emili and Edward Marcotte, a University of Texas, Austin, professor of molecular biosciences, led a landmark Nature study that revealed tens of thousands of new protein interactions across nine animal species—baker’s yeast, amoebas, sea anemones, flies, worms, sea urchins, frogs, mice, and humans. Using mass spectrometry to analyze cell samples from each species, the researchers found which proteins worked together in networks and compared their structures across species. Their map provided clues to how these protein associations evolved over time.
“Andrew’s work is highly relevant to a broad range of questions in both basic and applied biomedical research,” says Michael Sorenson, a CAS professor of biology. As an evolutionary biologist, Sorenson says, he particularly appreciates Emili’s 2015 Nature study and how it “beautifully illustrates the way in which animal diversity has evolved by building upon and tweaking a common set of fundamental cellular processes that has functioned in much the same way for a billion years or more.”
Emili came to BU from the University of Toronto, where he was a professor of molecular genetics and the Council of Ontario Universities Ontario Research Chair in Biomarker Discovery. He was also a principal investigator and a founding member of the Donnelly Centre for Cellular & Biomolecular Research. He earned a PhD in molecular and medical genetics from the University of Toronto in 1997 and pursued postdoctoral studies as a Damon Runyon/Walter Winchell Cancer Research Fellow with cell geneticist Leland Hartwell, a Nobel laureate, at the Fred Hutchinson Cancer Research Center in Seattle, where Hartwell is president and director emeritus. During that same period, Emili learned protein mass spectrometry with John Yates III, then a University of Washington School of Medicine associate professor of molecular biotechnology, now a Scripps Research Institute professor of chemical physiology.
“BU has tremendous resources,” says Emili, “and given the widespread community support, I think the center can leapfrog ahead and chart out some exciting new terrain to claim and explore.
“Let’s see what riches this initiative will yield.”