The NIH has awarded three grants totaling $31.8 million over five years to multidisciplinary teams of researchers based at University of California, San Diego, and elsewhere toward the agency’s new 4D Nucleome Program, the school said today.

The 4D Nucleome Program is a collaborative research initiative aimed at better understanding how DNA is arranged within the cell’s nucleus in four dimensions—three-dimensional space plus time—and how changes in that nuclear organization affect human health and disease. The program is composed of six separate but interrelated initiatives that encompass 29 awards to 24 different institutions throughout the U.S.

The largest share of the announced NIH funding, $20.2 million, was awarded to UC San Diego’s Institute of Engineering in Medicine to establish the Nucleome Network Organizational Hub at the school. The hub will integrate the efforts of all the 4D Nucleome Program’s funded initiatives and promote cooperation and communication among participants.

Together with the NIH, the hub team will also fund, manage and coordinate research proposals within the Opportunity Pool, a portion of the total award amount that will be distributed as sub-awards to support new projects and initiatives addressing identified needs that could arise during the lifetime of the program.

The organizational hub will also create a web portal and serve as a community-wide resource and point of access for all data, protocols, reagents, resources and methods developed by 4D Nucleome Program investigators nationally and globally. This work will be done in coordination with another one of the six program initiatives, the Data Coordination and Integration Center, UC San Diego said.

Principal investigators for the grant are Sheng Zhong, Ph.D., associate professor of bioengineering; Shu Chien, M.D., Ph.D., distinguished professor of bioengineering and medicine and director of IEM; Shankar Subramaniam, Ph.D., distinguished professor of bioengineering, computer science and engineering, and cellular and molecular medicine, and Bing Ren, Ph.D., professor of cellular and molecular medicine and Ludwig Cancer Research member.

Another $8.6 million over five years was awarded to UC San Diego and Ludwig Cancer Research to establish the Nuclear Organization and Function Interdisciplinary Consortium, another of the program’s six initiatives.

The Consortium’s goal is to support the formation of interdisciplinary teams to create the next generation of high-throughput technologies that can produce dynamic three-dimensional maps of mammalian genomes. All of the technology and data generated by this initiative will be made available to 4D Nucleome Program participants and the broader biomedical research community via the organizational hub, UC San Diego said.

Principal investigators for the Consortium grant include Dr. Ren; Cornelis Murre, Ph.D., distinguished professor of biological sciences; and Olga Dudko, Ph.D., associate professor of physics, in collaboration with Ana Pombo, D.Phil., of Max Delbruck Center for Molecular Medicine; Ming Hu, Ph.D., of New York University School of Medicine; and Mario Nicodemi, Ph.D., of University of Naples Federico II.

A third 4D Nucleome Program initiative, Imaging Tools, will involve Mark Ellisman, Ph.D., distinguished professor of neurosciences and director of the Center for Research on Biological Systems at UC San Diego, together with project lead Clodagh O’Shea, Ph.D., of the Salk Institute for Biological Studies.

Both institutions will receive a total of $3 million over five years to fund the project, in which Drs. Ellisman and O’Shea and their teams will work to create genetically encoded metal nanoparticles and novel paints. The nanoparticles and paints are intended to light up genes of interest within the maze of DNA, enabling their structures to be visualized so that researchers can see, for the first time, the structure of a gene within the intact nucleus.

The analysis and storage of these visual genome atlases will be facilitated by the program’s organizational hub, UC San Diego said.

“At the successful completion of the 4D Nucleome Project, we will be in a position to make more accurate predictions about how each individual person’s DNA contributes to the unique appearance of that person and his or her disease risks,” Dr. Ren said in a statement.

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