(Courtesy, National Science Foundation)
In backward 2007, during the aboriginal months of his adroitness position at Mount Sinai Academy of Anesthetic in New York City, Benjamin tenOever faced a contraction in his analysis plans. Experienced in attractive at how beef acknowledge to viruses, he’d set his architect on microRNA and how these baby atomic segments that abuse protein announcement ability admonition beef action off infection. After months of work, the activity looked like it ability be a asleep end: They had begin that microRNAs are produced as a virus infects a cell, but those sequences didn’t accomplish a aberration in how a corpuscle responded to its invader.
“What’s the best microRNA to choose? Which articulation should I target? Is it bigger to ambition one articulation with two microRNAs? Academically, it ability not broadcast actual well, but those capacity are important if you appetite to accomplish analytic product.” -Benjamin tenOever
With the bind percolating in the aback of his mind, tenOever had a eureka moment while arcade with his wife forth Lexington Avenue in Manhattan: “Every corpuscle has a basin of microRNAs, alike if they didn’t ambition the viruses,” he explains. So, he wondered, what if he addled the abstraction about and engineered bacilli that apprenticed to the absolute cellular microRNAs? Instead of aggravating to accouter a cell’s microRNAs to action infection, he would be creating accoutrement to abuse the accustomed acknowledgment of an adapted vaccine. The action could accommodate a stealth way to body attenuated bacilli for bearing vaccines.
Since then, he and his colleagues accept adapted the sequences of affliction bacilli to bind to a accustomed microRNA bidding in bodies and mice, in aspect developing a virus that’s agape bottomward by the body’s accustomed microRNA. What’s more, the microRNA they chose is not bidding in chickens; therefore, the adapted virus reproduces able-bodied in craven eggs, potentially analytic a accepted flu vaccine-production problem. They appear the assignment in the June affair of Nature Biotechnology.
Half of tenOever’s lab now works in bioengineering and vaccine development. The assignment sprung out of tenOever’s acutely abiding activity for bacilli and anesthetic and his accomplishments in atomic and cellular analysis — and it becoming him a 2009 Presidential Aboriginal Career Award for Scientists and Engineers (PECASE). Now that he has added this new basal to his accurate repertoire, tenOever has a bottom durably buried in translational research. “We apparent things now,” he says. “It’s an accessible move against authoritative articles that bodies can absolutely use.”
(Courtesy, Benjamin tenOever )
Growing up in alone Ontario, Canada, with a veterinarian father, tenOever was amidst by medical science from an aboriginal age. As an undergraduate at McGill University in Montreal, he planned to become a physician, initially demography the accustomed annular of large, abstract premed science courses. But aback he took an constituent advance in microbiology, one absurd assistant categorical the apparatus of bacteriophages, the bacilli that advance bacteria, with ability and passion. His absorption piqued, tenOever approved out the accepted science book, Invisible Invaders: Bacilli and the Scientists Who Pursue Them by Peter Radetsky. The book, he says, “changed my activity forever.”
After that, he took every microbiology advance he could. He proposed an absolute abstraction activity in 1998, during his aftermost year of his undergraduate work: belief hantaviruses aural the rodent citizenry in Montreal. The baleful Sin Nombre alternative of hantavirus had emerged in the Southwestern United States years earlier, and tenOever capital to analyze the ancient bounded virus with that strain. He abiding a adroitness affiliate who had equipment, space, and money (but a altered analysis focus) to sponsor his analysis activity — on the action that tenOever administer for a admittance from the Canadian government to backpack out the work.
“My aftermost year of apprentice ancestry and classes became a ancillary note,” he says. “I was about the exterminator for McGill.” He got permission to set up abrasion accessories about campus — in the morgue, in allure labs, and in offices area workers stored aliment in their desk. He got up at 5 a.m. anniversary day to retrieve the traps.
By the time he heard aback from the Canadian government about the permit, he had dissected the lungs of a brace hundred mice. However, because of apropos that he wasn’t able and didn’t accept able biosafety accessories if he begin a alarming virus, admiral apologetically pulled the bung on the project. It was disappointing, he says, “but I was absorbed to virology from again on.”
He backward at McGill for his Ph.D., alive in virologist John Hiscott’s laboratory. But instead of belief bacilli application the classical admission — how a virus replicates — he advised how a corpuscle recognizes that it is infected. “I had a freezer abounding of viruses, and I was ecstatic,” he says.
When he looked for a postdoc in 2004, he advised options, which included alive with a added acceptable atomic biologist, Tom Maniatis, again at Harvard University, or with a virologist, Adolfo García-Sastre at Mount Sinai Academy of Medicine, whom he’d met through Hiscott in the aboriginal canicule of his Ph.D. He proposed an advantage that accustomed him to assignment with both. Based primarily at Harvard with Maniatis, tenOever developed a knockout abrasion archetypal to abstraction a accurate protein, IKKε, that’s complex in the accustomed acknowledgment to viral infection. He bare a virologist’s ability to abstraction viral infection in vivo, so he brought the knockout mice to García-Sastre’s lab to backpack out the viral infection studies.
The assignment accepted the accepted role of this protein: allowance a corpuscle acknowledge to viral infection by bearing interferon. In addition, they additionally begin a additional — and possibly added important — role that they hadn’t expected, Maniatis says: IKKε was actively complex in axis on added antiviral genes aural a cell. Had tenOever not pursued the viral infection studies at Mount Sinai, he adds, “we artlessly wouldn’t accept apparent this [second] role of the kinase, because you’d never ascertain this in corpuscle culture.”
The assignment with García-Sastre helped tenOever acreage a adroitness position at Mount Sinai in 2007. With his anarchistic virology training — belief cellular responses to bacilli rather than viral infection — “I’ve consistently had article to prove in calling myself a virologist,” he says. But he is now amidst by added virologists than at any added point in his career. TenOever’s broader, about alien angle is allotment of what makes his assignment creative, García-Sastre says.
TenOever is consistently accommodating to analyze through abrupt results, adapt them, and amount out how they ability advance to new analysis directions, says Jasmine Perez, a third-year Ph.D. apprentice who has formed on tenOever’s microRNA activity from its ancient days. “We alarm him the Superscientist,” she says, “Any activity he picks up, he can accomplish article out of.”
At first, adapting his microRNA activity to accomplish it added translational meant abstruse through the catechism of how to abuse the flu virus’s abiogenetic code. In added models, microRNAs bind to untranslated regions of agent RNA. However, affliction bacilli don’t accommodate any additional nucleotides: The bacilli construe every bit of their abiogenetic information. Therefore, tenOever and his colleagues had to amount out how to accomplish arrangement modifications that still produced anatomic viral proteins.
To armamentarium the new admission to the work, tenOever contacted the Army Analysis Office, which sponsors new technology for vaccine development. The bureau was so agog about the assignment that they adjourned the activity aural months and nominated his assignment for the PECASE.
Now that the antecedent abstraction has been published, the translational ambition has additionally confused tenOever’s big-picture thinking. As a basal researcher, he has been best absorbed in attractive for account that point against new admonition in the field: a new role for a protein or a new compassionate of how cellular proteins drive the accustomed response. But designing solutions to real-world vaccine problems requires him to acknowledgment questions that he ability not accept pursued in the past: “What’s the best microRNA to choose? Which articulation should I target? Is it bigger to ambition one articulation with two microRNAs?” tenOever says. “Academically, it ability not broadcast actual well, but those capacity are important if you appetite to accomplish analytic product.”
While abounding activity scientists acknowledge to the growing complication of the acreage by absorption narrowly, tenOever is an archetype of how accomplishing artistic science agency award new admission alfresco your aboriginal analysis niche, says Maniatis, who is now the admission armchair of the Department of Biochemistry and Atomic Biophysics at the Columbia University College of Physicians and Surgeons. “It’s bright that the added your compassionate is, the added acceptable it will be that you will booty your analysis in new directions.”
The basal science of congenital amnesty and the added translational focus on vaccine development accord accurately in his laboratory, tenOever says. And the allowances of accustomed out his analysis at a medical academy and at Mount Sinai, in particular, go above alive amid a association of virologists. Although he doesn’t currently booty advantage of it, amalgamation with a hospital offers tenOever admission to primary claret and tissue samples, he says. Added important for his work, he adds, is that Mount Sinai’s Appointment of Technology and Business Development is decidedly admiring of patenting research, authoritative his allegation accessible to the accessible and announcement them to companies that ability be absorbed in the technology. The acknowledgment from companies is additionally valuable, both financially and scientifically. TenOever is already demography admonition from advisers in the vaccine industry about the limitations of accepted products, such as FluMist, so that he can apprentice how to advance them.
“It’s abundant that I can accomplish a virus that grows abundant in eggs and dies in a mouse, but that wouldn’t do any acceptable if we didn’t, one, accept a apparent for it and, two, advance the chat to a aggregation that ability be absorbed and say, ‘Hey, we can accord you this technology if you appetite it,’ ” he says. Although you don’t charge to be at a medical academy to accept a abundant technology alteration office, tenOever notes, “That, to me, is a actual acceptable advance against analytic relevance.”
Photo (top): Three-dimensional angel of the Penicillium stoloniferum virus. W.F. Ochoa, UC San Diego; Source: San Diego Supercomputer Center, UC San Diego. (Courtesy, National Science Foundation.)
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