EFRI-MIKS: Multiscale Analysis of Morphogen Gradients

EFRI-MIKS：形态发生梯度的多尺度分析

• 批准号: 1136913
• 负责人: Stanislav Shvartsman
• 金额: $ 200万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1136913&HistoricalAwards=false
• 关键词: EFRI; MIKS; Multiscale; Analysis; Morphogen

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.

新兴领域的研究和创新方面的NSF奖支持旨在解决发展生物学基本问题的工作：是什么控制细胞分化的空间和时间模式？对该问题的严格研究对于了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南是必要的。越来越多的工程和合成生物学方法引起了形态基因梯度的概念，该方法定义为分子的浓度谱，这些分子提供了对基因表达的剂量依赖性控制的分子。在实验上，该范式最初是在早期的果蝇胚胎中建立的，我们将其用作模型系统。我们建议研究形态植物如何模拟胚胎的背腹轴，并将其细分为引起肌肉，神经和皮肤组织的领土。通过在更深层次的定量层面上理解该系统，我们将阐明驱动开发的遗传和多细胞网络运行的一般原则。我们工作的更广泛影响在于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的跨学科培训。由该奖项资助的学生和博士后研究员将接受跨学科培训，这将为他们在开发系统生物学快速新兴领域的独立职业做好准备。作为这一重要领域的培训的一部分，我们将开发研究生和本科课程，这些课程使用早期的胚胎发展来介绍组织开发和调节的遗传，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的科学家和工程师，从事多细胞信号的分子和系统级方面的工作。