The HHMI Interactome See how the new class of investigators is grouped by field and study system. Mouse over each illustration to learn more about the scientist. View Interactome Credit: Peter Arkle

In June, Kim, a developmental biologist at Stanford University, was chosen to become one of 56 new HHMI investigators. The 42 men and 14 women at 31 U.S. research institutions represent a $600-million commitment over the next five years by HHMI. They will join the roughly 300 HHMI investigators doing research at institutions across the country and the resident scientists at HHMI's Janelia Farm Research Campus in northern Virginia. HHMI's goal is nothing less than transformative science. Investigators are expected to jump ahead of conventional thinking, extend the boundaries of science, and carve out new prospects. Success requires brains, creativity, skill, a little luck, and a great deal of nerve.

The lives of the HHMI investigators are adventure stories of a 21st century kind. Gone are the heroics of the early 20th century microbe hunters who offered their arms to pathogen-loaded insects and their innards to self-experiments; yet, modern researchers face their own set of hazards. They risk being wrong. They risk a long education on a short career in a blind alley. They risk missing the big discovery. But when those risks pay off … the results can be stunning.

Seung Kim risked starting from the wrong premise. He probes the developmental roots of diabetes by studying the progenitor cells that differentiate into insulin-producing islet cells. In the human pancreas, these islet cells measure glucose levels and respond with molecules like glucagon and insulin to regulate metabolism. Diabetes is a human metabolic disorder but Kim believes there are common mechanisms conserved through evolution by which all animals control their cellular energy levels.

A pioneer in culturing new islet cells in mice and from human pancreatic cells, Kim reasoned that if he could compare two widely separated model organisms—fruit flies and mice—with human islet cells, he could trace the development of their shared metabolic controls. When Kim first proposed using flies for a developmental study of diabetes, no one knew if Drosophila had the equivalent of a human endocrine system. Revealing the cellular and molecular basis of the fly's endocrine system and metabolic regulation was the first leg of Kim's journey to become an HHMI investigator.

Jue Chen risked getting nowhere. Chen, a structural biologist who resolves the shape of biologically important molecules by x-ray crystallography, launched her career at Purdue University on a long shot. Chen admits that for seven years she was obsessed with the maltose ABC transporter, a mysterious but powerful protein complex that ferries sugar molecules through the cell membrane to the cell's interior. Biochemists and geneticists had stacked up data for decades that gave them an excellent idea of what the maltose ABC transporter should be doing, yet no one had ever produced atom-by-atom images of the transporter in action. When Chen arrived at her first faculty position at Purdue, she made that her goal. Her scientific mentors were worried. The maltose transporter might be too narrow a target. One warned that, as a junior researcher, Chen could be “betting the farm” on a problem that was beyond current technology.

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