With gift, Broad Institute to open ‘Cell Observatory’
Scientists are launching an ambitious effort to diagram how the human genome controls cells by tracing the chemical pathways it uses to send instructions zinging through them like balls in a pinball machine.
The Broad Institute, a biomedical research juggernaut in Cambridge that is affiliated with Harvard University and the Massachusetts Institute of Technology, announced today a $32.5 million gift from the Klarman Family Foundation to open a “Cell Observatory.” The center will allow researchers from Boston and around the world to investigate the molecular contents – not just the genes, but also the many chemicals that interact with them – of different human cell types, using large-scale techniques available only in advanced labs.
“When people want to look at the stars, they reserve time in observatories to do their measurements and analyze the data,” said Aviv Regev, the project’s lead researcher. “There are many types of cells out there, and you need expertise to observe and analyze them, too. This would be a place where instead of looking at constellations in the sky, people could look at constellations in the cells.”
The ultimate goal is to catalog all the biochemical circuits inside human cells and to determine which configurations lead to disease.
As a start, the Broad Institute will designate a space in its Kendall Square building where scientists can gather to exchange ideas and use existing and new equipment. Some researchers at Harvard, MIT, and the area’s teaching hospitals are already working together; others will be recruited.
Several other major research institutions, including the Mt. Sinai School of Medicine in New York, the Salk Institute in La Jolla, California, and the University of California, San Diego are considering similar plans. There is talk of a “Human Circuit Project” in which centers would coordinate and share data as they did in sequencing the first human genome.
“The task at hand is enormous -- mapping pathways is much larger, more ambitious and ill-defined a goal than the Human Genome Project,” said Trey Ideker, a systems biologist at UCSD who is running an early parallel initiative. “Thus there is lots and lots to do.”
It is a task that could take a lifetime to complete, like deciphering who is whispering what to whom in thousands of simultaneous games of “telephone.” In theory there are more possible configurations of genetically-driven networks than there are atoms in the universe (in reality there are probably just hundreds or thousands).
The networks are not static. They respond to stimuli such as drugs and hormones, rearranging themselves as cells interact with the outside world. “It’s like connecting the dots, but now think of the dots coming out of the page in three dimensions and then changing into a different picture,” said Joseph Ecker, a biologist who studies biochemical networks in plants and humans at the Salk Institute.
At least one analogous attempt to study cell circuitry in mice was made in the mid-2000s, with older technology and consequently limited success.
But researchers inside and outside the Observatory said its time has come.
Seth Klarman, the Boston hedge fund manager whose foundation is underwriting the project’s first phase, is known for making careful bets and winning them big. (Though little-known to the general public, he is a star among financial analysts, who buy copies of his lone, out-of-print book for thousands of dollars on Amazon.) His family’s foundation, chaired by his wife Beth, has supported biomedical science before. It funds one of the nation’s largest centers for treatment and research on eating disorders at McLean Hospital in Belmont. Klarman also sits alongside Nobel laureates on the Broad Institute’s board.
The grant will enable the new project by bringing together at least two groups: physicians and scientists with specialized knowledge of diseases or cell types, and other researchers with the technological and computational expertise that increasingly drives much of modern biology.
Researchers can now spy on cells in unprecedented detail, piecing together their life stories by silencing genes one by one and measuring how that changes the cells’ behavior. They can tell what makes an immature cell specialize and stay that way. They can compare sick cells with healthy ones, looking for signatures of illness that point to causes and possible cures.
The approach is so rooted in the fundamentals of cell biology that it could someday be applied to almost any disease. Regev has already begun to find networks in two cell types – blood stem cells and a specialized type of immune cell – on which the center may focus its early work.
However, understanding other cell types, such as those found in the liver and brain, poses a larger challenge, in part because they are difficult to grow in the lab.
Unraveling biochemical networks takes money and time -- much more so than sequencing a genome, said Brad Bernstein, a Massachusetts General Hospital pathologist who has collaborated with Regev to study how genes are turned on and off. “We’ve had enormous interest from scientists who want to tap into our capabilities,” he said. “But it takes substantial resources to open up your doors and let everyone else come in and play.”
It also takes statistical know-how that even the smartest computational biologists do not yet have. “It’s not a question of computing power. That will come,” said Ideker. “The question is, is there enough brainpower?”
Even if the project succeeds wildly, researchers said, it may leave many questions unanswered. It will certainly lead to new ones. “What’s happening at the cell level is important, but how do those cells interact with each other in complex tissues? How are those tissues interacting in the organ, and how do the organ systems interact at the organism level?” said Eric Schadt, a prominent geneticist and systems biologist at Mt. Sinai. “My first reaction to this is, ‘very cool.’ But it’s one component of complexity. It’s necessary for understanding. It’s not sufficient.”
Mary Carmichael can be reached at firstname.lastname@example.org. Her Twitter feed is mary_carmichael.
Correction: Because of a reporting error, this Page One story about a Klarman Family Foundation gift to the Broad Institute incorrectly described another recipient of the group’s largesse. The Klarman Eating Disorders Center at McLean Hospital is primarily a treatment program, though the foundation also supports a national program that funds research on eating disorders.