Süel Gürol
University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Methods Enzymol. 2011;497:275-93. doi: 10.1016/B978-0-12-385075-1.00013-5.
The physiological processes and programs of cells are not typically determined by single genes, but are governed by the patterns of interactions between genes and proteins [Alon, U. (2007). An Introduction To Systems Biology: Design Principles of Biological Circuits. Chapman & Hall/CRC, Boca Raton.]. These interactions are commonly referred to as genetic circuits, and the pattern of these interactions is called the circuit's architecture [Sprinzak, D. and Elowitz, M.B. (2005). Reconstruction of genetic circuits. Nature438(7067), 443-448.]. Genetic circuits control diverse cellular processes, and each process requires specific dynamic behaviors to properly function. Biochemical evidence aids in the identification of interactions between genes and proteins, but the spatiotemporal dynamics of these interactions are more difficult to probe using conventional techniques. Fluorescence time-lapse microscopy is a powerful tool in the study of genetic circuit dynamics, allowing the measurement of circuit dynamics in single cells [Suel, G.M., et al. (2007). Tunability and noise dependence in differentiation dynamics. Science315(5819), 1716-1719.]. Uncovering the dynamics of genetic circuits allows verification of mathematical models of genetic circuits and aids in the design of forward experiments. By enabling the study of relationships between circuit architecture and dynamic behavior, fluorescence time-lapse microscopy opens new frontiers in synthetic biology, allowing for the alteration of genetic circuits to achieve novel behaviors [Cagatay, T., et al. (2009). Architecture-dependent noise discriminates functionally analogous differentiation circuits. Cell139(3), 512-522.], and even the generation of completely synthetic, purpose built genetic circuits [Elowitz, M.B. and Leibler, S. (2000). A synthetic oscillatory network of transcriptional regulators. Nature403(6767), 335-338.]. Perhaps more importantly, determination of genetic circuit dynamics can reveal the concepts and principles underlying the biological functions they regulate.
细胞的生理过程和程序通常并非由单个基因决定，而是由基因与蛋白质之间的相互作用模式所调控[阿隆，U.（2007年）。《系统生物学导论：生物电路的设计原理》。查普曼与霍尔/CRC出版社，博卡拉顿]。这些相互作用通常被称为遗传电路，而这些相互作用的模式则被称为电路的架构[斯普林扎克，D.和埃洛维茨，M.B.（2005年）。遗传电路的重建。《自然》438(7067)，443 - 448]。遗传电路控制着多种细胞过程，并且每个过程都需要特定的动态行为才能正常发挥功能。生化证据有助于识别基因与蛋白质之间的相互作用，但使用传统技术更难探究这些相互作用的时空动态。荧光延时显微镜是研究遗传电路动态的强大工具，能够测量单个细胞中的电路动态[苏埃尔，G.M.等人（2007年）。分化动态中的可调性和噪声依赖性。《科学》315(5819)，1716 - 1719]。揭示遗传电路的动态有助于验证遗传电路的数学模型，并辅助正向实验的设计。通过能够研究电路架构与动态行为之间的关系，荧光延时显微镜为合成生物学开辟了新的前沿领域，使得改变遗传电路以实现新行为成为可能[卡加泰，T.等人（2009年）。依赖于架构的噪声区分功能类似的分化电路。《细胞》139(3)，512 - 522]，甚至能够生成完全合成的、专门构建的遗传电路[埃洛维茨，M.B.和利布勒，S.（2000年）。转录调节因子的合成振荡网络。《自然》403(6767)，335 - 338]。也许更重要的是，确定遗传电路的动态可以揭示它们所调控的生物学功能背后的概念和原理。
