Construction and analysis of synthetic eukaryotic gene regulatory networks

合成真核基因调控网络的构建与分析

• 批准号: 313172-2011
• 负责人: Kaern, Mads
• 金额: $ 2.91万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571806
• 关键词: Construction; analysis; synthetic; eukaryotic; gene

The term "synthetic biology" is used to describe a field of research at the interface between disciplines ranging from applied mathematics and physical biology to molecular genetics and systems biology. The central dogma of the field is based on a principle of reverse engineering: optimal insight into the operation and design principles of a complex system can be gained by breaking the system into smaller parts, characterizing these parts in isolation, and reassembling them to understand how they work together. However, synthetic biology research does not limit itself to the study of natural systems. Rather, it explicitly seeks to create artificial systems that endow living organisms with novel functionalities. This biological systems engineering is based on the premise that DNA-encoded "parts" can be isolated and assembled into functional "devices", which, in turn, can be combined into larger circuits. The proposed research aims (1) to better understand how variations in DNA-encoded parameter values and regulatory control mechanisms impact the function of genetic networks, (2) to improve the realism of computational models describing such systems, and (3) to expand on the number of parts available for DNA-based biological engineering in higher organisms. The project goals will be achieved through interdisciplinary research and training programs, integrating components of mathematics, physics, engineering and biology at both the graduate and undergraduate level. We are specifically interested in investigating signal and noise propagation in genetic networks and exploring the interplay between noise and epigenetic inheritance in cellular stress-responses. The knowledge and resources developed through our proposed research is likely to generate new insights into the intricacies of gene regulation, and will contribute directly to the further development of eukaryotic synthetic biology.

“合成生物学”一词用于描述从应用数学和物理生物学到分子遗传学和系统生物学等学科之间的交叉领域的研究领域。该领域的中心法则基于逆向工程的原理：通过将系统分解为更小的部分，单独表征这些部分，然后重新组装它们以了解它们如何协同工作，可以获得对复杂系统的操作和设计原理的最佳洞察。然而，合成生物学研究并不局限于自然系统的研究。相反，它明确寻求创建赋予生物体新功能的人工系统。这种生物系统工程的前提是，DNA 编码的“部件”可以被分离并组装成功能性“设备”，而功能性“设备”又可以组合成更大的电路。 拟议的研究旨在（1）更好地了解 DNA 编码参数值和调节控制机制的变化如何影响遗传网络的功能，（2）提高描述此类系统的计算模型的真实性，以及（3）扩大高等生物中基于 DNA 的生物工程可用的部件数量。该项目的目标将通过跨学科研究和培训计划来实现，整合研究生和本科生的数学、物理、工程和生物学的组成部分。我们特别感兴趣的是研究遗传网络中的信号和噪声传播，并探索细胞应激反应中噪声和表观遗传之间的相互作用。通过我们提出的研究开发的知识和资源可能会对基因调控的复杂性产生新的见解，并将直接促进真核合成生物学的进一步发展。