A synthetic approach to developmental patterning

发育模式的综合方法

• 批准号: 7055460
• 负责人: DAVID SPRINZAK
• 金额: $ 5.2万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055460
• 关键词: Caenorhabditis elegans; bacteria; biological models; cell cell interaction; cell differentiation; developmental genetics; eukaryote; model design /development; postdoctoral investigator; prokaryote

DESCRIPTION (provided by applicant): Mechanisms of pattern formation in developmental systems generally combine complex intracellular genetic circuits with intercellular signaling. In many cases it is difficult to study these mechanisms due to the incomplete knowledge of the components involved and the inherent complexity of natural circuits. I propose to study these principles in a quantitative manner, using a synthetic network approach combined with microfluidic technology. I will initially develop an experimental platform with bacterial strains capable of sending, receiving, and interpreting diffusible signals combined with a microfluidic setup allowing well controlled and quantitative measurements of these strains. Different mechanisms for the formation of morphogen gradients will be studied; in particular their robustness to noise will be compared. I will then extend the system to eukaryotic cells by developing a synthetic signal transduction system. This signaling system will be used to study patterns based on juxtacrine signaling (direct cell-cell signaling). This study could provide a more quantitative understanding of the underlying principles of developmental patterning at the circuit level and may lead to biomedical applications in fields like tissue engineering.

描述（由申请人提供）：发育系统中模式形成的机制通常将复杂的细胞内遗传回路与细胞间信号传导结合起来。在许多情况下，由于对所涉及组件的了解不完整以及自然电路固有的复杂性，研究这些机制很困难。我建议使用合成网络方法与微流体技术相结合，以定量的方式研究这些原理。我最初将开发一个实验平台，其中的细菌菌株能够发送、接收和解释可扩散信号，并结合微流体装置，可以对这些菌株进行良好的控制和定量测量。将研究形态发生素梯度形成的不同机制；特别是对它们对噪声的鲁棒性进行比较。然后，我将通过开发合成信号转导系统将该系统扩展到真核细胞。该信号系统将用于研究基于近分泌信号（直接细胞间信号）的模式。这项研究可以更定量地理解电路水平上发育模式的基本原理，并可能导致组织工程等领域的生物医学应用。