CAREER: Towards Synthetic Biology in Human Stem Cells

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

CBET-1350178 Saha, Krishanu Human stem cells provide an attractive, patient-matched source for generating many tissues found in the body, but controlling stem cells in culture remains a key challenge. To meet this challenge, this proposal seeks to develop and apply synthetic biology tools in order to dissect and precisely control the complex molecular signaling processes that determine stem cell behavior in culture. Synthetic biology is an emerging biotechnology field that combines elements of engineering, mathematics, chemistry, and biology to synthesize novel systems from characterized biological components. Applying new synthetic biology tools in human stem cells to control cell behavior would enable advanced manufacturing of patient-specific tissues and cells for disease modeling and drug discovery applications. This proposal outlines a novel approach to convert natural signaling components in human stem cells to synthetic, bioorthogonal ones. The approach relies on producing mutations in cells at defined genomic locations. Such an approach allows for the formation of libraries of mutant cells that can be selected for particular functions. The proposal focuses on a fundamental barrier to establishing a robust stem cell tissue engineering and bioprocessing industry ? manipulating cell signaling pathways when stem cells grow in culture and come together with other cells and materials. The research will be integrated into education by developing and disseminating course modules demonstrating the importance of cross-disciplinary training in stem cell biology, engineering and bioethics for postgenomic approaches to human biomedicine. The proposal to incorporate underrepresented students into the research laboratory and to advance new curriculum will help to develop the next generation of students trained at the stem cell biology-engineering interface. Due to the interdisciplinary nature of the project, this CAREER award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology.