EFRI-MIKS: Multiscale Analysis of Morphogen Gradients

由研究和创新新兴前沿办公室颁发的NSF奖支持旨在解决发育生物学的一个基本问题的工作：是什么控制了细胞分化的空间和时间模式？对这一问题的严格研究对于理解胚胎发生的基本原理、阐明发育障碍的起源以及为组织工程和再生医学提供合理的指导是必要的。越来越多的工程和合成生物学方法引用了形态生成梯度的概念，形态生成梯度的定义是提供对基因表达的剂量依赖控制的分子的浓度分布。在实验上，这个范式首先是在果蝇早期胚胎中建立的，我们使用它作为我们的模型系统。我们建议研究形态原如何形成胚胎的背腹轴，将其细分为产生肌肉、神经和皮肤组织的区域。通过在更深层次、更定量的水平上理解这一系统，我们将阐明驱动发育的遗传和多细胞网络运行的一般原理。我们工作的更广泛影响是在开发高通量和广泛可用的研究技术、建立公开可用的数据库以及对学生和博士后研究员进行跨学科培训方面。由该奖项资助的学生和博士后研究员将接受跨学科培训，为他们在迅速崛起的发展系统生物学领域的独立职业生涯做好准备。作为这一重要领域培训的一部分，我们将开设研究生和本科课程，利用早期胚胎发育来介绍组织发育和调节的遗传学、计算和工程研究的一些关键思想。我们的研究提供的严格培训将有助于新一代科学家和工程师在多细胞信号的分子和系统层面上工作。

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.