Chip-based Studies of the Interactions Between Neurotransmitters and Brain Model through Blood Brain Barrier

About This Grant

The U.S. population is aging, and millions are affected by neurodegenerative disorders, yet their causes remain largely unknown. Emerging research suggests that the gut microbiota plays a role in neurodegenerative processes by influencing brain pathophysiology. However, the mechanisms behind this microbiota-gut-brain axis (MGBA) are still poorly understood. Current studies of neurodegenerative diseases rely on animal models and clinical trials, which face major limitations such as ethical concerns, high costs, low throughput, and significant time and labor demands. Hence, it is essential to develop alternative in vitro platforms to study interactions between gut microbiota and brain tissue models, thereby enabling deeper insight into the MGBA. The educational goal of this project is to integrate research with education to train both undergraduate and graduate students in interdisciplinary studies to produce next-generation bioengineers. The investigators will incorporate this work into their existing Vertically Integrated Program (VIP), Targeting Neurodegenerative Diseases Using Bioengineering Approaches. Building on years of mentorship experience, they will engage undergraduate, graduate, and K–12 students in interdisciplinary research. The aim is to equip students with strong technical knowledge and hands-on lab skills to support their future careers. The goal of this proposal is to develop a new, on-chip reductionist model to evaluate the essential role of gut microbiota and its interactions with in vitro brain models through an in vitro blood brain barrier (BBB). This platform will facilitate the studies of the interactions between the microbiota and an in vitro brain model that will permit the investigation of mechanisms of organ development, cellular interactions, and disease model progression under the influence of the microbiota within microenvironments. Specifically, the proposed efforts include (1) the development of a chip consisting of chamber arrays to mimic the bidirectional communication between the gut bacteria/microbiota and brain in vitro; and (2) the studies of the behavior of brain models under the influence of the microbiota using this chip. Major innovations of this proposed project include: (1) Using this type of chip, large-scale studies of the interactions between gut bacteria/microbiota and brain models can be performed rapidly and inexpensively; (2) Using the integrated sensors on-chip, the concentrations of the metabolites specifically the neurotransmitters produced by microbiota can be determined quantitatively in real-time; and thus (3) Using this chip will facilitate the quantitative studies of the effects of these biologically active chemicals on both healthy and diseased brain models. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.