Duke Researchers Join $30M Project to Uncover Hidden Layers in the Human Genome

Adapted from Northwestern University’s press release

The U.S. National Science Foundation (NSF) has awarded $30 million over five years to a consortium of universities to establish a new center aimed at uncovering a hidden layer of information within the human genome.

Housed at Northwestern University and called the Center for Genome Intelligence Engineering (GENIE), the Science and Technology Center (STC) will integrate experts in physics, biology, engineering, artificial intelligence (AI) and medicine to understand how the genome’s 3D structure helps cells establish their identities, remember past experiences and respond to their environments.

GENIE’s national network of researchers ultimately will aim to manipulate this architecture to improve human health. The approach could lead to new ways to help cells withstand injury, restore lost function and regenerate tissues without changing their underlying DNA.

The new STC is led by Northwestern biomedical engineer Vadim Backman and includes co-principal investigators Tatiana Segura (Duke University), Nicola Neretti (Brown University) and Jorge A. Cantu (Northeastern Illinois University).

“Northwestern’s long tradition of integrating disciplines has made it a natural home for work that treats the genome as both a physical structure and a computational system,” Backman said. “GENIE will extend that convergence across institutions, bringing together people and capabilities that no single field or university could assemble on its own to learn how to read and write this language of life, opening new possibilities for regenerative health, healthy longevity and disease treatment.”

GENIE will pursue this work through three integrated research thrusts: understanding the genome’s foundational physics; developing technologies in imaging, computation and AI; and engineering chromatin. Researchers then will put their discoveries to the test in three crosscutting testbeds focused on human health: strengthening cells against injury caused by reduced blood flow, rejuvenating neurons in models of Alzheimer’s disease and regenerating heart muscle cells and neurons affected by aging.

The research pursued at Duke will focus on delivering test beds for electrically active heart and brain cells for collaborators across the center to use to explore these concepts. Both cell types are difficult to repair and do not spontaneously regenerate, leaving behind scar tissue in the heart and empty cavities within the brain after injury.

Segura has a long history of developing novel biomaterials to encourage the regrowth and repair of brain tissue. This has primarily been accomplished through her lab’s microporous annealed particle, or MAP, platform, which provides pathway to studying how engineered materials can physically influence cells and their nuclei. The approach recently showed promising results for healing brain damage in mouse models after strokes.

“Through Duke’s Materials in Medicine Center, we are developing the biomaterials expertise and shared resources needed to connect material design with cellular behavior,” said Segura, the Robert Plonsey Distinguished Professor of Biomedical Engineering. “Within GENIE, MAP allow us to investigate how changes in cell shape, mechanical forces and the nuclear environment affect genome organization and cellular memory. This work could establish new principles for designing materials that help damaged tissues restore function and regenerate.”

Joining Segura in the GENIE center from Duke is Nenad Bursac, professor of biomedical engineering, who is a leading expert in growing functional human heart and muscle tissues in laboratory environments. Bursac’s lab was the first to grow human tissue-engineered myobundles and cardiobundles and has since demonstrated their potential for use in uncovering mysteries of rare muscle diseases and testing gene therapies to heal damage after heart attack.

“Our cardiac and neuronal cell culture models and animal models of disease will be used for the collection of large genomic datasets that will enable fundamental understanding of disease- and aging-related changes in cell memory,” Bursac said. “Moreover, these model systems will serve as testbeds for new methods to restore heart and brain function in aging populations and to minimize tissue damage from heart attacks and strokes.”

Because genome geometry is physical, GENIE researchers will explore ways to physically reshape it. One approach will use CRISPR-based tools to change how regions of chromatin interact and fold — without editing the DNA itself. Another will investigate whether low-energy electromagnetic fields — delivered from outside the body — can be used to influence chromatin organization. A third will use engineered biomaterials to physically reshape cells and, in turn, the genome inside them.

Beyond providing test beds, Segura and Bursac will also be major contributors to the third thrust. Their research platforms will be a key part of investigating how the physical reshaping of genomic memory may be the primary mechanism of action for early promising results observed in various biomaterials developed to promote regeneration.