Uncovering Morphogenetic Modularity with Data Science

How do tissues acquire their intricate shapes and functions, and how do disruptions in these processes lead to congenital disorders? Understanding the principles that drive tissue morphogenesis is essential for tackling challenges in developmental disorders, regenerative medicine, and synthetic biology. This project centers on the concept of modularity—the idea that tissue formation relies on a finite set of cellular behaviors, such as division, migration, and shape change, which are reused and adapted to build diverse tissue architectures. By leveraging modularity as a unifying framework, this research seeks to uncover how cells organize into functional modules during early brain and epidermal development in the Drosophila embryo. We focus on two complementary systems: the brain and the epidermis. In the brain, we aim to identify patterns of cell division, migration, and differentiation that coordinate neurodevelopment. These patterns will illuminate universal principles of brain morphogenesis and provide a foundation for understanding how disruptions in these processes contribute to congenital disorders. In the epidermis, we will analyze modularity by investigating how morphogenetic cell activities are reused, combined, or specialized to drive tissue diversity. By addressing how a finite repertoire of cellular modules balances conservation and innovation, we aim to uncover the principles that enable diverse tissue architectures. Central to this effort is the development of a machine learning-based algorithm for cell segmentation and tracking from 3D live-imaging datasets generated using light-sheet microscopy. This novel tool is critical for overcoming longstanding technical challenges in tracking cell lineages over time, enabling us to reconstruct dynamic cellular behaviors across entire embryos. These reconstructions will provide the foundation for identifying and analyzing cellular modules in unprecedented detail, directly supporting our modularity-focused investigations. Aligned with the MIRA mechanism’s emphasis on flexibility and innovation, this work integrates expertise in live imaging, computational biology, and developmental genetics to pioneer a modularity-based framework for understanding morphogenesis. By addressing foundational questions in developmental biology, this research has the potential to transform our understanding of tissue formation and its disruptions in disease, while enabling new applications in synthetic biology and medicine. Project Number: 1R35GM162152-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Tomer Stern | Institution: UNIVERSITY OF MICHIGAN AT ANN ARBOR, ANN ARBOR, MI | Award Amount: $400,881 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MCST-G (56)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11269617