Left to right: Simon John, Jackson Laboratory; Peter Walter, University of California, San Francisco; Xiaowei Zhuang, Harvard Unviversity; Huda Zoghbi, Baylor College of Medicine.

HHMI investigator Catherine Dulac, of Harvard University, will use the new funding to lead a team of neuroscience experts in studying the impact of gene imprinting—a phenomenon in which only a single gene copy is expressed rather than both chromosomal copies—on behavior and brain development. She's collaborating with three other Harvard researchers who specialize in how neurons make decisions, the role of genetics in neurological disorders, and the evolutionary role of imprinting in the embryo. By some estimates, the team could find 600 or more genes controlled by imprinting, but Dulac doesn't really know what they'll find.

“I have been thinking for many years about the mechanisms of gene regulation—such as imprinting—and the coevolution of neuronal function and behavior,” she says. “This has triggered the interest of several colleagues with very different fields of expertise, who can now brainstorm and test key hypotheses together.”

HHMI plans to evaluate the progress of the eight collaborative projects selected for this pilot phase and expects to expand the program in coming years. Philip Perlman, a senior scientific officer at HHMI who oversees the program, stresses that such funding is valuable because scientists often hesitate to undertake large collaborations, which can be seen as detracting from a lab's primary focus. “Many research groups find it difficult to allocate resources to allow one or more members to devote years to a project that could yield important results but may never directly further the lab's own mission,” says Perlman.

Reinberg, who now has to make room in his lab for boxes of ants frozen in liquid nitrogen and shipped from Arizona, loves his new collaboration because it allows him to study new areas—like neuroscience. “I have been working in cells for more than 20 years,” he says. “And now I have the opportunity to work on whole organisms and move into neurobiology. This project has opened the door for my next 20 years of science.”

		Douglas Rees, of the California Institute of Technology, is leading a team of three experts in structural biology and protein chemistry to develop a novel way to solve the three-dimensional structures of proteins embedded in membranes. Such proteins are vital to cells—they act as gatekeepers between compartments and between the cell and its surroundings—but they are notoriously hard to work with. Peter Walter, at the University of California, San Francisco, an expert in protein folding, will enlist five collaborators in San Francisco and Chile to probe whether it's possible to target drugs to different steps of the pathway that guards cells against misfolded proteins. Susan Lindquist, at the Whitehead Institute for Biomedical Research, wants to find strategies to target the biological mechanisms that break down in Parkinson's disease and other neurodegenerative disorders. Her long-term goal is to develop personalized treatments for patients. Partners include stem cell expert Rudolf Jaenisch and colleagues at the University of Alabama, Boston University, and Purdue University. Huda Zoghbi has a plan for speeding up drug discovery. Her team, at Baylor College of Medicine and the University of Minnesota, is working on a rapid way to identify hundreds of genes involved in clearing disabled proteins from the brain—a process that goes awry in Parkinson's disease. “If we can figure out the neurobiology for one of these diseases, it can then be applied to many of the other neurodegenerative disorders,” says Zoghbi. Xiaowei Zhuang, whose Harvard University lab develops imaging techniques, is taking a closer look at the brain. By collaborating with creators of some of the most powerful and innovative methods for imaging, data analysis, and sample preparation, Zhuang seeks to map out all the neural connections in mammalian brains.

Photos: John: Michael C. York / AP ©HHMI, Walter: George Nikitin / AP ©HHMI, Zhuang: Cheryl Senter / AP ©HHMI, Zoghbi: Bob Levey / AP ©HHMI.

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