UChicago research teams receive grants to map every cell type of the human gut

Two University of Chicago research teams have received funding from The Leona M. and Harry B. Helmsley Charitable Trust to contribute to building a Gut Cell Atlas, a collaborative effort that aims to define every type of cell in the human ileum (the last part of the small intestine) and colon.

The projects are part of the Human Cell Atlas, an international effort by experts in biology, computation and medicine to map all the cells in the human body. The resulting cellular and molecular map will help researchers better understand what goes wrong when disease strikes.

One grant awards $2.9 million over three years to geneticists Oni Basu, PhD, and Sebastian Pott, PhD; computational scientist Matthew Stephens, PhD; and renowned inflammatory bowel disease researcher Eugene B. Chang, MD, to catalog the human gut cells of healthy patients and those with Crohn’s disease.

Single cell genomics for the gut

Basu is a pioneer in the field of single cell genomics, a technique that isolates single cells from a tissue sample and then sequences DNA individually instead of the tissue as a whole. There are several known classes of cells in the gut, such as epithelial cells and immune cells; however, each of these classes may have several sub-types that respond differently to disease. Basu and Pott are also working in a similar project as part of the Human Cell Atlas to map heart cells.

The researchers will use tissue samples taken from patients during routine colonoscopies or as part of their treatment for Crohn’s disease. Basu and Pott, with computational support from Stephens, will compare the results of their single cell genomics analysis with gut organoids developed in Chang’s lab. These miniature organs are small clusters of intestinal cells that can be grown from samples taken from patients. If the organoids turn out to be accurate representations of the single cell types, they can serve as proxies for testing treatments on the patients’ own tissues at distinct points of time or stages of disease.

“Crohn’s disease isn’t just one single disease. It presents in many different forms,” Basu said. “Characterizing the cells of the gut and seeing how the disease affects them, and at different stages in the progression of the disease, can help find better, more tailored treatment options.”

Mapping the gut brain axis

A second grant awards $324,000 to support neuroscientist Bobby Kasthuri, PhD, to image all the cells in the terminal ileum and the colon over the next year. Kasthuri is known for his work studying the connectome, a detailed map of connections between every neuron in the brain. During the course of that research, his team has developed techniques to prepare samples of brain tissue, automate the production of imaging by X-ray and electron microscopy, and process the resulting data with software algorithms.

Kasthuri’s team will apply the same imaging technology and computational tools used to map the brain to the tissues of the gastrointestinal tract, specifically samples removed during surgery from patients with and without Crohn’s disease. They will trace the connections between nerves and muscle cells in the gut as well as gain insight into how tissue organization changes with disease.

“We know that neurons in the intestine communicate with each other, with the muscle cells of the digestive tract, with the lining of the intestine and with the immune system,” Kasthuri said. “Understanding the specifics of how these cells communicate in both healthy tissue and how they change in disease can give valuable insights into the inner workings of Crohn’s disease.”

The Helmsley Charitable Trust’s Crohn’s Disease Program supports impactful ideas and mobilizes a global community committed to improving the lives of Crohn’s disease patients while pursuing a cure.

“The Gut Cell Atlas will offer unparalleled insights into what we know about ourselves and our gut, including the role of each cell in keeping us healthy – or causing disease,” said Garabet Yeretssian, PhD, Director of Helmsley’s Crohn’s Disease Program. “Both teams at the University of Chicago will play a key role in mapping the cells of the gut – a critical step to realizing Helmsley’s goal of finding precise, personalized, and effective treatments for Crohn’s disease patients, while pursuing a cure.”

For more information, please visit helmsleytrust.org.