The National Science Foundation is establishing a major research center to investigate how the physical folding and organization of DNA within cells influences which genes turn on or off, potentially opening new pathways to treat Alzheimer's disease, cardiovascular disease, and cancer. The Center for Genome Intelligence Engineering, or GENIE, led by Northwestern University, is one of three new NSF Science and Technology Centers receiving a combined $90 million investment over five years.

Why Does DNA's 3D Shape Matter More Than Just Its Sequence?

Most people think of DNA as a simple linear instruction manual, but that's only half the story. Inside the cell nucleus, DNA must fold, twist, and organize itself into a complex three-dimensional structure. This physical arrangement determines which genes become accessible to the cell's machinery and which remain hidden. GENIE researchers aim to understand how this three-dimensional organization influences cell identity and function, and how disruptions in that structure contribute to disease.

The center will receive approximately $6 million annually during the initial five-year period and can compete for up to five additional years of additional support. By supporting a center rather than individual projects, the NSF is creating a structure for sustained collaboration across multiple institutions and disciplines, bringing together researchers who might otherwise work in isolation.

What Research Methods Will GENIE Use to Study Genome Organization?

GENIE's work will combine multiple complementary approaches to examine how DNA organizes itself and how that organization influences health and disease. The research will integrate experimental techniques with computational analysis, creating a comprehensive toolkit for understanding genome structure at unprecedented detail.

• Sequencing Technologies: High-throughput DNA sequencing methods will identify which genes are active in different cell types and how their accessibility changes with genome organization.
• Advanced Microscopy: High-resolution three-dimensional imaging will allow researchers to visualize chromosome structure directly within living cells, revealing the physical architecture of the genome.
• Computational Modeling: Researchers have already developed generative artificial intelligence methods for predicting chromatin structures, and GENIE will expand these computational approaches to understand genome organization at scale.
• Genome Manipulation: Direct editing and modification of genome structure will help researchers test whether specific organizational changes cause or prevent disease.

How Will GENIE Coordinate Research Across Multiple Institutions?

Running a multi-institutional research center creates significant operational challenges alongside scientific opportunities. Teams across different laboratories will need to coordinate experimental protocols, metadata standards, data formats, and quality control procedures to ensure that results generated at different sites can be reliably compared or combined. Sample provenance, instrument settings, software versions, and analysis parameters can all affect how researchers interpret and reproduce genome-organization findings.

The combination of experimental and computational work makes data infrastructure a central consideration. Sequencing and imaging generate large, complex datasets that require substantial storage capacity, computing power, clear data retention policies, and specialized analytical staff. Lab managers supporting this work will need to plan for shared equipment access, preventive maintenance, cross-training, and scheduling across workflows with different turnaround times. Clearly assigned responsibility for method changes and data review will be essential when multiple disciplines contribute to a single result.

What Diseases Could GENIE's Research Help Address?

GENIE's focus on understanding how genome organization influences cell identity and function has direct implications for several major diseases. Changes in genome structure have been linked to Alzheimer's disease, cardiovascular disease, and cancer. By understanding the normal three-dimensional organization of DNA and how it becomes disrupted in disease, researchers hope to develop new strategies to help cells and tissues withstand damage, restore lost functions, or return to healthier states.

The center will also contribute to the NSF's broader workforce mission by providing students and early-career researchers with hands-on experience in emerging technologies. This training in cutting-edge genomics, computational biology, and collaborative research will help develop the next generation of scientists equipped to tackle complex biological challenges.

GENIE represents a shift in how the NSF supports genomics research, moving beyond funding individual laboratories toward building sustained, multi-disciplinary research ecosystems. By bringing together expertise in sequencing, microscopy, computational modeling, and genome engineering under one coordinated center, the NSF is betting that understanding the three-dimensional organization of DNA will unlock new insights into how cells work and how disease develops.