Lin He: “Junk” DNA isn’t

The child of Western-trained engineers, Lin He grew up in a Beijing very different from today's skyscraper megalopolis. She recalls the freedom of the outdoors, the remnants of ancient city walls, and the fl ying kites. Like many others born in that era, He aspired to become an important scientist like the mathematicians and technologists who were then China's national heroes. Having long planned to pursue her studies abroad, He leapt at the chance when offered a scholarship at Stanford University for her PhD. The revelation that microRNAs (miRNAs) impact mammalian gene expression brought He to the forefront of efforts to decode the function (1–3) and regulation (4, 5) of noncoding genomic elements. It's becoming increasingly clear that we can no longer afford to think of these portions of the genome as " junk " DNA, He explained when we called her at her lab at What links your graduate work on mouse pigmentation with your current work on miRNAs? I feel that technology is a key driving force that shapes how science develops. When I worked with Greg Barsh, one major technology in mamma-lian genetics—particularly mouse genetics—was using positional cloning to correlate genetic alterations and phenotype. Gene targeting was not easy back then, so people relied on spontaneously generated mouse mutants to study development and disease. Mouse pigmentation is a particularly enriched trait; mouse genetics started with mouse fanciers and their collections of mice with distinct pigmentation patterns , and coat color regulation utilizes similar molecular pathways as many other biological processes. So, one can gain insights into diverse developmental and physiological processes by identifying coat color genes using positional cloning. But it takes three or four years of hard work to identify a gene and study its function by this method, so I really desired a technology that would allow us to do this more effi ciently. [Laughs] When I graduated from Stanford in 2003, the emerging RNA interference (RNAi) technology promised to allow the systematic knock-down of every single gene in the genome and screening for a particular phenotype. I wanted to do that so badly! So after interviewing at all the major RNAi labs I joined Greg Hannon's lab to work on RNAi screens in mammalian systems. RNA interference, not miRNAs? I worked on RNAi for about a year but my main project didn't go anywhere because we were not quite ready to use RNAi as …