Press Release October 12, 2015

JAX Genomic Medicine receives $3.7 million federal grant to develop a new system for understanding the 3D genome

A five-year, $3.7 million grant was awarded to a team led by Professor Yijun Ruan, Ph.D., of The Jackson Laboratory for Genomic Medicine to fund research into how the human genome is organized in the nucleus of the cell.

Composed of DNA, the genome in a single cell would stretch to more than six feet in length if extended. Instead it is intricately looped and physically packed into microscopic nuclei. This three-dimensional (3D) structure is thought to play many important roles in genome regulation and function.

Ruan is the Florine Deschenes Roux Chair Professor and director of genomic sciences at The Jackson Laboratory. An international leader in genome structure research, he is developing a new system for understanding 3D genome organization and regulation.

A chromatin interaction cluster mediated by protein factors as a topological stuctural and functional unit for coordinated transcription regulation. Illustratin by Katherine Fuller.
A chromatin interaction cluster mediated by protein factors as a topological structural and functional unit for coordinated transcription regulation. Jackson Laboratory image by Katherine Fallon.

The grant is part of the 4D Nucleome program, supported by the National Institutes of Health’s Common Fund  to investigate nuclear organization in space and over time (the fourth dimension, or 4D).

Ruan says. “We know now that there are complex interplays between DNA, protein factors and RNA species, together shaping the precise but ever-changing 3D genome conformation within the tiny nuclear space. We have a great deal to learn about how such structure is organized and how it affects gene expression in normal development and disease.”

Ruan’s team includes co-investigators Chia-Lin Wei, Ph.D., of Lawrence Berkeley National Laboratory, Paul Blainey, Ph.D., of the Broad Institute and Rafael Casellas, Ph.D., of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Together they will develop a comprehensive, high-resolution mapping program that will deliver complex interaction network maps that can provide insight into the dynamics of individual genomic elements in the context of 3D genome structures.

Called the Nucleome Positioning System (NPS), the program will comprise a genome-wide mapping technology platform, integrated computational modeling algorithms, cutting-edge nuclear imaging methods and advanced functional validation approaches. The resulting tools and mapping data will be made available to the larger research community and help establish the standards for future 3D/4D nucleome studies.

The grant provides $749,775 for the first year of research, and provisional funding for an additional four years.

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number U54DK107967. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.