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Leonardo Morsut

University of California
Development of a toolkit for multicellular synthetic biology in mammalian cells
Morsut1, L., Roybal1, K., Lim1, W.

1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, USA


Multicellular biological systems display very interesting and useful morphological and functional features (e.g. the brain architecture, tissue regeneration). The analytical study of the layers of influences (from genetic, to epigenetic, to mechanical, to environmental) is being carried out at greater and greater detail. Yet, on the synthetic side, the capacity to directly program multicellular behaviors from the bottom-up is in its infancy. The promise of this engineering approach is two-fold: improve knowledge of the logic of developmental processes with an "understanding by building" approach, and provide innovative routes for regenerative medicine approaches. Two main components are needed for the implementation of the synthetic program: a molecular toolkit whose design is user-defined (to define the local communication and behavior rules for the cells); and a theoretical framework to map the emergent properties (morphology, functionality, etc.) onto those local rules. The latter is being developed across many different fields; I focused on the development of a specific toolkit for multicellular synthetic biology in mammalian cells.

The molecular tools will be orthogonal to endogenous pathways and user defined. One class of tools I am developing consists of optogenetic control over key developmental pathways; the optogenetic approach provides the user with a great level of temporal and spatial control over cell behavior in multicellular systems. The second class are orthogonal cell-cell communication channels, including cell-cell contact mediated signals and diffusible signals; these will allow the user to design the interaction and behavior rules for the cells to follow during the multicellular dynamic process of self-organization. All these orthogonal channels are then used to systematically construct and modulate interactions in multicellular models.

HFSP Long-Term Fellow (Award year 2012)
Fellow: MORSUT, Leonardo
Host supervisor: LIM, Wendell