Abstract
Short bowel syndrome is a malabsorptive disorder caused by an insufficient length of functional small intestine, most often following extensive surgical resection. A possible therapeutic strategy is to stimulate crypt fission, the process by which new intestinal tissue is generated. Our aim is to investigate diverse approaches—such as helminth infections and mechanical tension—that promote crypt fission and thereby expand the absorptive surface area of the small intestine in mice. To this end, we developed a novel three-dimensional spatiotemporal imaging method for whole tissue segments of mouse small intestine. Subsequent image analysis was performed using supervised machine learning–based segmentation. Preliminary results suggest that intussusceptive angiogenesis supports crypt fission, thereby enabling regeneration of tissue to compensate for lost absorptive function.

Biosketch
Julian Louis Muff is an MD-PhD student at the University of Basel whose research focuses on investigating novel treatment strategies for short bowel syndrome. His research examines how the small intestine adapts to external cues, particularly mechanical stress and tissue growth driven by type 2 immunity. He has established collaborations between the University Children’s Hospital of Basel, the University of Zürich, and Stanford University. As a Research Scholar at Stanford University, Julian developed a mechanical model to promote crypt fission—a key process in intestinal tissue growth. At the University of Zürich, he explores the immunological dimension of tissue adaptation by studying helminth– tuft-cell – ILC2 interactions both in vivo and in vitro, integrating machine learning–based imaging techniques of whole mount tissue samples with CRISPR-Cas9 genetic manipulation of mouse and human organoids.