NSF Reproducible Cells and Organoids via Directed-Differentiation Encoding RECODE
Preliminary proposal required November 22, 2021
Directorate for Engineering
Division of Chemical, Bioengineering, Environmental and Transport Systems
Division of Civil, Mechanical and Manufacturing Innovation
Directorate for Biological Sciences
Division of Molecular and Cellular Biosciences
Division of Integrative Organismal Systems
The RECODE solicitation will support activities that substantially advance our capability to direct cell differentiation to a specific functional endpoint through the integration of synthetic biology, advanced sensing and control, and cellular and tissue modeling. Studies that not only use these approaches to test ideas in differentiation but also concomitantly confront new challenges in the contributing scientific areas within the framework of cell differentiation will also be considered. The proposed research should go well beyond that typically supported by a single core NSF program in the participating Directorates. A key objective of this solicitation is to encourage sustained collaboration among the diverse fields of engineering, biology, and biophysics necessary to develop a holistic differentiation control framework. To that end, proposed research submitted in response to this solicitation is expected to bridge the topics supported by the Division of Chemical, Biological, Environmental, and Transport Systems Engineering Biology and Health programs, as well as related programs in the Divisions of Molecular and Cellular Biosciences, Integrative Organismal Systems, and Civil, Mechanical, and Manufacturing Innovation. Proposals are expected to be submitted by multidisciplinary teams of no less than three investigators. At least one member of the project team (PI or co-PI) must have a full-time, tenured, or tenure-track faculty appointment within a college or department of Engineering.
The process of differentiation involves a multiplex combination of signaling molecules, receptors, promoters, markers, and chemical and mechanical regulators that dynamically interact to direct cell development and behavior. While individual inducers of native differentiation have been identified and employed to create specialized cell types, we generally lack fundamental understanding of the roles of biochemical and environmental regulators necessary for synthetic induction of differentiation along a predetermined path and the ability to actively monitor and manipulate that path dynamically. Such control of differentiation will be valuable to answer mechanistic questions about basic biological processes that govern physiological function and development of specific cells, tissues, and organs, as well as mechanisms for processes involved in immunity (e.g., symbiosis versus disease, immunological responses to infection).The control of differentiation will also enable the realization of enhanced biomanufacturing, leading to novel products, biomaterials, and significant improvements in individualized medicine, environmental control and monitoring, adaptive sensing, as well as the scalable and reproducible application of 3D organoids in drug testing.