Measuring Islet-wide Function with Soft Integrated Nanoelectronics
Contact PI: Juan Alvarez, PhD, Harvard University
Start Date: March 2021
HIRN Emerging Leader Award Recipient
Defects in hormone secretion by pancreatic islet alpha and beta cells are an early sign of their dysfunction/loss due to islet-directed autoimmunity in type 1 diabetes (T1D). Elucidating the mechanisms underpinning the development and coordination of alpha and beta cell hormone secretion will thus help us understand, and eventually prevent, their deregulation during T1D onset and progression. We propose to combine integrated bioelectronics and controlled in vitro islet maturation to understand how islet-wide alpha and beta cell activities evolve as they reach their full secretory potential. Integrating state-of-the-art tools for generating islets with custom alpha-beta composition from stem cells and for chronic simultaneous recording of cellular activities across whole-islet volumes, will inform: (1) how human alpha and beta cells first gain regulated hormone secretion capacity; (2) how secretory activities change and become coordinated during maturation; and (3) how these properties are lost in T1D. Our innovative platform at the interface of nanoelectronics and stem cell biology will serve as a powerful tool to fully capture human islet development, to establish better models for diabetes, and ultimately to propel advances in stem cell-based diabetes therapeutics.