A research team at UC Santa Barbara has received a major grant from Wellcome Leap, announced on Mar. 19, to join a global initiative examining how the early-life gut microbiome may influence neurodevelopmental challenges such as autism spectrum disorder.
The project is part of Wellcome Leap’s Foundations of Resilient Microbiome (FORM) program, which focuses on understanding the role of the gut microbiome during pregnancy through age two—a period when this microbial ecosystem rapidly develops and may impact immune, metabolic, and neurological systems. The program seeks to determine if disruptions in the early-life microbiome contribute to neurodevelopmental differences and whether resilience in these formative years can be measured or supported.
Led by Michelle O’Malley, professor of chemical engineering and interim chair of the Bioengineering Department, the UC Santa Barbara team will use high-throughput experimental systems to study how early microbial communities respond to environmental exposures. Their work integrates engineering, microbiology, physics, mathematics, ecology, and clinical science. “This program is exciting because it allows us to take the kind of bold, non-incremental steps that traditional funding models rarely support,” said O’Malley. “Wellcome Leap is explicitly focused on making big leaps in understanding. In this case, that means asking whether the early-life microbiome plays a causal role in neurodevelopment, and how resilience during this critical window might be better supported.”
The research will utilize ExFAB—the Biofoundry for Extreme & Exceptional Fungi, Archaea, and Bacteria—an automated facility established with National Science Foundation funding. This infrastructure enables cultivation of complex gut microbial communities under controlled conditions for systematic testing. “We’re essentially creating miniature, highly controlled versions of the gut so we can challenge them with different early-life environments — such as components of breast milk or antibiotic exposure — and observe how these communities evolve,” O’Malley said.
Jean Carlson and Holly Moeller lead efforts to analyze data using modeling approaches from physics and ecology. “When you can observe how a system evolves, you can start to see which early changes actually matter, and which ones don’t,” Carlson explained. Combining mechanistic modeling with machine learning aims to move beyond correlation toward causal understanding. “Bringing together mechanistic modeling with the statistical power of machine learning and AI is a powerful combination and gives us a way to transform thousands of experiments into insight,” Carlson added.
Collaboration with Ty Vernon and Fernanda Castellón at UC Santa Barbara’s Koegel Autism Center ensures clinical perspectives are included. Vernon said: “This research offers the opportunity to move beyond speculation and toward data-driven understanding of how early biological systems interact with neurodevelopment… The knowledge provides a critical missing link that can help families, clinicians and educators make more informed decisions that support the neurodivergent community’s well-being and quality of life.”
Campus leaders highlighted interdisciplinary collaboration as key to advancing discovery. Chancellor Dennis Assanis said: “We are honored to have the partnership and transformative support of Wellcome Leap… It is a shining example of the interdisciplinary collaborative research that is a hallmark of our campus.” Umesh Mishra noted: “Ex-FAB gives our faculty the ability to generate and analyze complex biological systems at unprecedented scale.” Jill Sharkey emphasized community impact: “The inclusion of professors Vernon and Castellon ensures that groundbreaking biological research is directly informed by clinical expertise…” Dean Shelly Gable added: “These researchers are asking a genuinely important question about the roots of neurodevelopment…”
O’Malley clarified that their goal is not to “cure” autism but deepen scientific understanding: “We’re trying to understand the biological mechanisms of neurodivergence so we can better support individuals and families… That includes recognizing strengths while also asking whether early biological insights could expand options for promoting health.”
Ultimately, researchers hope their findings will guide future conversations about supporting neurodivergent individuals based on scientific evidence.
