UC San Diego was awarded a $20.2 million, five-year grant Monday to establish an organizational hub for a wide-ranging federal study on how DNA is arranged in a cell's nucleus, and how changes in the structure impact human health and disease.
The National Institutes of Health 4D Nucleome Project is composed of six separate, but interrelated, initiatives that encompass 29 awards to 24 institutions in the U.S. The "4D" refers to the three dimensions of space, plus time.
UCSD researchers will receive one quarter of the program's funding to lead the program's organizational hub and contribute to two of the research initiatives.
"Thanks to very recent technological advances, we now have the imaging and sequencing tools needed to directly visualize and measure miniscule and dynamic structures in the nucleus that play important roles in gene regulation and functional modulation in health and disease," said Shu Chien, a UCSD professor of bioengineering and medicine.
"A group of outstanding experts — including physicists, engineers, biologists, bioinformaticians, clinicians — will utilize these tools and develop new ones to create an entirely new interdisciplinary approach aimed at better understanding the nucleome and the potential it holds for personalizing the prevention, diagnosis and treatment of disease," Chien said.
According to UCSD, most known genetic risk factors for disease are located in the non-coding regions of human genomes, in which a major function is to regulate when and how to turn certain genes on or off. Little is known about how that works in space and time.
The 4D Nucleome Program is designed to develop technologies, resources and data to determine how the genetic arrangements and timing are coordinated, as well as how aberrations in the nucleome contribute to human health or disease risk.
The organizational hub at UCSD will integrate the efforts of all the 4D Nucleome Programs funded initiatives and promote cooperation and communication among participants.
Of the two other UCSD-led initiatives receiving funding, an $8.6 million NIH grant will establish the Nuclear Organization and Function Interdisciplinary Consortium, which seeks to create technologies that can produce dynamic three-dimensional maps of mammalian genomes.
A $3 million award will go to researchers at UCSD and Salk Institute for Biological Studies of La Jolla to create molecular beacons that will light up genes of interest within the maze of DNA, which would allow researchers to see the structure of a gene within an intact nucleus.
