EFRI-MIKS: Multiscale Analysis of Morphogen Gradients

Princeton University, Princeton NJ

Investigators

Abstract

The NSF award by the Office of Emerging Frontiers in Research and Innovation supports work designed to address a fundamental question of developmental biology: what controls the spatial and temporal patterns of cell differentiation? Rigorous studies of this problem are necessary to understand basic principles of embryogenesis, to elucidate origins of developmental disorders, and to provide rational guidelines for tissue engineering and regenerative medicine. An increasing number of engineering and synthetic biology approaches invoke the notion of morphogen gradients, defined as concentration profiles of molecules that provide dose-dependent control of gene expression. Experimentally, this paradigm was first established in the early Drosophila embryo, which we use as our model system. We propose to study how morphogens pattern the dorsoventral axis of the embryo, subdividing it into the territories that give rise to the muscle, nerve, and skin tissues. By understanding this system at a deeper, quantitative level, we will elucidate general principles underlying the operation of genetic and multicellular networks that drive development. The broader impacts of our work are in the areas of developing high-throughput and broadly available research technology, in the establishment of publicly available databases, and in the interdisciplinary training of students and postdoctoral fellows. Students and postdoctoral fellows funded by this award will receive interdisciplinary training that will prepare them for independent careers in the rapidly emerging field of Developmental Systems Biology. As part of training in this important field, we will develop graduate and undergraduate courses that use early embryonic development to introduce some the key ideas of genetic, computational, and engineering studies of tissue development and regulation. Rigorous training provided by our studies will contribute to the new generation of scientists and engineers working on both molecular and systems-level aspects of multicellular signaling.