Nynke L. van Berkum, PhD, a post-doctoral researcher in the lab of Job Dekker, PhD, won the silver medal in a national collegiate invention competition for the Hi-C technique, which allows scientists to study how a six-foot-long strand of human DNA can fold into a tiny nucleus of a cell in an efficient and functional way. Dr. Van Berkum shares the $10,000 award with her collaborator, Erez Lieberman-Aiden, a graduate student in the Harvard-MIT Division of Health Science and Technology. The award was one of six honors given to 10 finalists—both graduate and undergraduate, individuals and teams—by Invent Now, Inc., in its 2010 Collegiate Inventors Competition, presented on Wednesday, Oct. 27, at the National Press Club. Hi-C enables a global, three-dimensional view of how genomes fold inside the nuclei of cells. “Being able to analyze the 3D structure of the genome will help us understand what is going wrong in genome organization in various diseases and Hi-C may even turn into a diagnostic tool in the future,” said Van Berkum. The technique has already revealed that errors in genome folding can be detected in cancer tumors.
Scientists have also shown how cells with identical genomes, like skin cells and neurons, perform entirely different functions. “Hi-C has shown that genome folding is a part of the answer to this question, because of our discovery that active and inactive genes are spatially separated into two nuclear compartments,” wrote Van Berkum and Lieberman-Aiden in their application.
Hi-C is the only method capable of determining the global folding of an entire genome, Van Berkum said, because whole genomes are too large to be studied using the traditional tools of structural biology: X-ray crystallography and nuclear magnetic resonance spectroscopy. Dr. Dekker, associate professor of biochemistry & molecular pharmacology and molecular medicine, is one of the research pioneers of this technology.
Van Berkum and Lieberman-Aiden first used formaldehyde to link together DNA strands that are nearby in the cell’s nucleus. They then determined the identity of the neighboring segments by shredding the DNA into many tiny pieces, attaching the linked DNA into small loops, and performing massively parallel DNA sequencing.
“By breaking the genome into millions of pieces, we created a spatial map showing how close different parts are to one another,” said Van Berkum. “We made a fantastic three-dimensional jigsaw puzzle and then, with a computer, solved the puzzle.”