Three Hertz Fellows Help Create The First 4D Map of Genome Folding

The Fannie and John Hertz Foundation, a not-for-profit organization dedicated to empowering America’s most brilliant scientific minds, is pleased to recognize the groundbreaking work of three of its Fellows, Suhas Rao, Dr. Erez Lieberman-Aiden and Dr. Jesse Engreitz. Rao, Aiden and Engreitz are three members of a team that created the first high-resolution 4D map of the human genome as it folds over time, which could lead to new ways of understanding genetic diseases. This project was supported by a Hertz Foundation Fellowship in conjunction with other funding and contributors, and was published in the October 5, 2017 issue of Cell.

Rao, Aiden and Engreitz, along with others at Baylor College of Medicine, Rice University, Stanford University and the Broad Institute of MIT and Harvard, began this work in 2014. At that point, they were able to map the DNA loops that result when DNA elements that lie far apart in the genome quickly find each other. But the maps were static, which made it difficult to determine how the genome folded in real-time.

In 2015, the team began disrupting cohesin, a ring-shaped protein complex located at the boundaries of nearly all DNA loops. Cohesin pulls DNA through its ring in a process call extrusion, forming and controlling the size of DNA loops. The process works quickly – the movement of cohesion along DNA is among the fastest for any known human protein.

By disrupting the function of cohesion, the team showed the role it plays in folding our DNA and determining which genes function in any given cell. When the team restored the function of cohesin, they mapped the DNA in space and time as it re-folded, creating striking images and a new understanding of how genes are regulated. These exciting discoveries will likely lead to additional genome research and work on genetic disorders.

“Hertz Fellows work tirelessly to transform our world for the better through science, math and engineering breakthroughs,” said Robbee Baker Kosak, president, the Fannie and John Hertz Foundation. “Our Fellowship supports transformational research, such as that undertaken by Suhas, Erez and Jesse, and the impact of that research is only magnified when our fellows work together. The entire Hertz community is proud of these gentlemen and excited to see what this work will bring in the future.”

Aiden is the director of The Center for Genome Architecture at Baylor College of Medicine, assistant professor of molecular and human genetics at Baylor College of Medicine, assistant professor of computer science at Rice University and assistant professor of computational and applied mathematics at Rice University. He studied mathematics, physics and philosophy as an undergraduate at Princeton and earned master’s degrees in history from Yeshiva University and applied physics from Harvard University. Aiden earned his PhD in applied math and biomedical engineering at Harvard and the Massachusetts Institute of Technology with the support of the Hertz Fellowship.

Rao is currently pursuing his MD/PhD at Stanford University School of Medicine and his PhD in quantitative biology at Stanford. He holds two fellowships: The Hertz Fellowship and the Paul and Daisy Soros Fellowship. Rao earned his undergraduate degree in applied mathematics from Harvard University. His PhD research includes understanding how the genome folds, the relationship between chromatin structure and gene regulation and the disorganization of the genome in various diseases. Rao ultimately wants to decipher the information contained in the genome and translate that into more precise modalities of patient care as a physician-scientist.

Engreitz is a Junior Fellow at the Harvard Society of Fellows, working at the Broad Institute of MIT and Harvard. He completed his PhD in bioinformatics and integrative genomics at Harvard University, in the Harvard-MIT Division of Health Sciences and Technology. He held two fellowships: The Hertz Fellowship and the National Defense Science and Engineering Graduate Fellowship. Engreitz earned his undergraduate degree in biomedical computation and master’s degree in bioengineering from Stanford University. His research focuses on uncovering the molecular mechanisms of autoimmune diseases through systematic studies of the noncoding genome and gene function.