by Elise Wachspress
Before the Olympian deities worshipped by the ancient Greeks, there were their ancestors, the Titans. The stories about both sets of gods would put our own Game of Thrones to shame for their high drama, grisly battles, multiple plot twists, and huge, convoluted casts.
The Titan Atlas led the Titanomachy, the war challenging the upstarts, which was decisive. The next-gen Olympians won, and Atlas was forced to carry the weight of the heavens—the universe, to the Greeks—throughout eternity.
Many centuries later, geographer Gerardus Mercator envisioned an encyclopedic portfolio of documents that included not just a collection of maps but also descriptions of the creation and form of the entire universe, or at least what was known of it in the middle of the sixteenth century. Mercator called his creation an “atlas,” named for the Titan who carried the heavens on his shoulders.
Since then, people have commonly called a book of maps an “atlas.” But, like Mercator’s original compendium, the best atlas is one that shows not just where, but how, when, and why.
In October 2016, a group of world-leading scientists met in London to discuss creating an atlas of the cells in the human body—a tool that would help describe and define the cellular basis of health and disease. Like the Human Genome Project, the Human Cell Atlas (HCA) initially looked like an overwhelmingly difficult quest. The scientists wanted to identify each unique cell type, describe how they work together to form tissues in three dimensions, and understand how all the body systems were connected. They needed to know which genes were active in which parts of the body and how each different cell type was produced.
As with the Human Genome Project, the only possible approach was to enlist a huge coalition of experts in biology, medicine, genomics, data analysis, software engineering, and visualization. Like the cast of thousands employed by Game of Thrones, groups would follow their own individual plot lines, coming together as the project grew.
Also like Game of Thrones, budgets would be high. Luckily, major foundations, including The Leona M. and Harry B. Helmsley Charitable Trust, the Wellcome Trust, the Chan Zuckerberg Initiative, and many others stepped in generously to make the work possible and accelerate progress.
The project would have been impossible without scientific breakthroughs in “single-cell technologies.” Researchers needed the ability to isolate individual cells, increase the amount of DNA and RNA within each sufficient for sequencing, see which genes were expressed (i.e., made into proteins) in each, and watch how those proteins powered that particular cell. Looking at a group of cells would just show how cells operated on average, with little information about how each individual cell contributed to the creation of tissues, organs, systems, immunity—and the health of the human person over all.
Anindita “Oni” Basu, PhD
Needless to say, many of the leaders in the new field of single-cell technologies are young, and UChicago has one of its pioneers. Anindita “Oni” Basu and her lab are not only adept at isolating and studying single cells, but they can do so quickly for multiple cells isolated from their native environments. Basu has profiled thousands of cells at a time, and, with her joint appointment at Argonne Laboratory’s Center for Nanoscale Systems, is constantly developing new tools to study inter-cellular interactions in complex biological systems.
Thus it was no surprise when Basu received a grant of nearly $3 million from the Helmsley Charitable Trust for a collaboration with other groups to help develop a “Gut Cell Atlas.” The goal is to better understand Crohn’s disease, a serious inflammatory bowel disease that causes abdominal pain, severe diarrhea, fatigue, weight loss, and even malnutrition. Basu and her team will not only identify and characterize gut cell types in those with and without Crohn’s, but also create “organoids,” lab-grown models of gut tissue, to study the mechanisms of Crohn’s disease in the lab and identify actionable targets for therapeutic interventions and disease prevention. Like Mercator’s atlas, the Gut Cell Atlas will be much more than a mere collection of maps.
Helming a large team that includes Crohn’s disease specialist Gene Chang, MD, and statistical geneticist Matthew Stephens, PhD, and set in an environment with a NIH-funded Digestive Diseases Research Core Center and strong clinical leadership in inflammatory bowel diseases, Basu has the perfect environment collaborate on building the Gut Cell Atlas.
It’s a big universe on Basu’s shoulders. But the knowledge she, her team, and others will develop over the next three years can create a foundation for new drug development and diagnostic tools, critical in an episodic disease like Crohn’s, where catching a flare-up early can significantly reduce disease progression. If her team can demystify the unknown, chart territories now marked “Here Be Dragons,“ and ultimately win this war, there will be smoother sailing ahead for the estimated three million people in the US with Crohn’s disease.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office
