“Does it have a meaning? How is that related to health? Is the genome folding the same way in all cells? How does it change in time?” Consider that the roughly two meters’ worth of double-helical DNA in each cell condenses 200,000- to 250,000-fold to fit in the nucleus, which has a diameter of 8 to 10 millionths of a meter or so. Roy, the 4D Nucleome project’s program leader. The packing problem invites a raft of fundamental questions, says molecular biologist and immunology researcher Ananda L.
“If you want to understand how a genome works, or even a chromosome, you have to understand its three-dimensional structure,” says chromosome biologist Job Dekker of the University of Massachusetts Medical School. With the recent start of its second phase, the effort’s overall funding amounts to some $280 million, involving dozens of research projects and hundreds of scientists. Add how this 3-D architecture changes with time and you get the fourth dimension. Health & Disease Arming immune foot soldiers against cancerĭriving the project are questions like these: How does our DNA pack itself so neatly within the cell’s tiny nucleus? How does it pack even tighter when it’s time for a cell to divide, and uncoil at just the right spots and moments in different cells to control, with precision, the activity of our 20,000-plus genes?Ī major push in this global effort, dubbed the 4D Nucleome program, was initiated by the US National Institutes of Health in 2015 out of a growing realization that parsing the 3-D architecture of the genome will be crucial for answering myriad questions about gene control across the human lifetime, in health and in disease.