完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | 李曉青 | en_US |
dc.contributor.author | Lee Hsiao-Ching | en_US |
dc.date.accessioned | 2014-12-13T10:43:06Z | - |
dc.date.available | 2014-12-13T10:43:06Z | - |
dc.date.issued | 2011 | en_US |
dc.identifier.govdoc | NSC100-2221-E009-028 | zh_TW |
dc.identifier.uri | http://hdl.handle.net/11536/99591 | - |
dc.identifier.uri | https://www.grb.gov.tw/search/planDetail?id=2332156&docId=366304 | en_US |
dc.description.abstract | 合成生物學是現代生物學的新興研究領域,其利用基因重組技術製造各種生物元件,組合成生物 IC電路,讓其依循可預期的方式表現出特定功能,控制細胞進行一系列的工作。現今架構生物IC電路 面臨的難題是生物電路在細胞內表現短暫功能後會逐漸崩潰,無法穩定運作於細胞中。基因表達時的 雜訊,不同RNA 剪裁、DNA突變及熱擾動等造成內在生化參數變動,以及細胞環境變遷與其他基因交 互作用所造成的干擾,都會使人工製造出來的基因電路無法穩定運作。因此如何設計可以忍受內在及 外界干擾的強健基因網路,是生物IC電路亟待解決的重要課題。為解決此問題,我們將建立數學模型 描述基因迴路動態行為,將回饋機制設計於基因迴路中,增加迴路輸出訊號之穩定性,降低不同細胞 間基因表現量的差異。之後利用實驗數據修正基因迴路運作的動態方程組,使基因迴路的表現可以由 數學模型模擬再現,進一步預測出不同基因迴路運作的動態形式。此外我們將選出有較低突變率的大 腸桿菌基因型,使基因迴路在宿主細胞中能穩定表現,達到控制生物行為的目標。 計畫主要目的為(1)建立多樣化的生物元件資料庫,以實驗量測DNA 元件之輸入輸出特性,以增 加生物元件的可控制性。(2) 降低基因迴路在宿主細胞的突變機率,增加基因迴路於宿主細胞中的穩 定性。(3) 利用回饋迴路設計強健性的基因迴路,使其能在內部雜訊及外加干擾存在下,還能持續穩 定表現。(4) 量測基因迴路輸入及輸出訊號,分析基因迴路調控的雜訊分佈,並找出在內部雜訊及外 部雜訊干擾下,還能有強健性的基因迴路設計。(5)利用實驗數據修正基因迴路運作的動態方程組,使 基因迴路的表現可以由數學模型模擬再現,進一步預測出不同基因迴路運作的動態形式。(6)將具有功 能性的基因迴路構築於大腸桿菌中,達到控制細菌行為的目標。 本計畫整合模擬及實驗,可定性及定量描述各生物元件及基因間的交互作用,由下而上更瞭解基 因網路間的調控方式,提出更佳方式在大腸桿菌中建構穩定的生物基因迴路。而且當生物元件資料庫 擴增後,可以依各元件特性,用電子電路設計概念,由生物元件資料庫中組合出最適合的基因迴路, 用來改造菌株。這項計畫的成果將可應用於設計經濟效益最佳的能源生產途徑,並拓展到產業應用。 | zh_TW |
dc.description.abstract | The main goal of the nascent field in synthetic biology is to design and construct biological system with a desired behavior. At present, even the construction of biological IC circuits has demonstrated the feasibility of synthetic biology, the design of gene networks is still a difficult problem and most of newly designed gene networks can not function properly. The major causes for these design failures are mainly due to both intrinsic perturbations such as gene expression noise, splicing, mutation, evolution and extrinsic disturbances such as changing extra-cellular environments, interactions with cellular context. Therefore, how to design a robust synthetic gene network to tolerate intrinsic parameter fluctuation and to attenuate extrinsic disturbances in order to function properly will be an important topic for synthetic biology. In this project, we will use controllable DNA parts and the feedback loop concept to increase stability of gene circuits in E. coli to meet this challenge. The objectives of this project are given as follows: (A) Establishing a library of well-defined DNA parts and defining the interaction function between promoters and ribosome binding sites. (B) Decreasing the mutation rate and increasing the stability of the genetic circuits in host cells. (C) Developing the robust genetic circuit design by the feedback loop concepts. (D) Measuring the input and output signals to analyze the noise distribution, and estimating the roust circuit design. (E) Constructing a synthetic gene network in host cells to verify and refine the robust biological circuit design. The experimental data can provide the mathematical properties of parameters and our team can refine the circuit design schemes to increase robustness of bio-systems. The stable and noise-resistance circuit design schemes have potential for applications, such as constructing a synthetic enzymatic pathway for drug production, and producing metabolic pathway in microbes that churn out bio-fuels. Design of genetic circuits is foreseen to revolutionize how we conceptualize and approach the engineering of biological systems. | en_US |
dc.description.sponsorship | 行政院國家科學委員會 | zh_TW |
dc.language.iso | zh_TW | en_US |
dc.subject | 合成生物學 | zh_TW |
dc.subject | 基因電路 | zh_TW |
dc.subject | 生物元件 | zh_TW |
dc.subject | 丁醇 | zh_TW |
dc.subject | Synthetic Biology | en_US |
dc.subject | genetic circuit | en_US |
dc.subject | biobrick | en_US |
dc.subject | butanol | en_US |
dc.title | 定義模組化DNA元件特性用已設計基因迴路與控制大腸桿菌行為 | zh_TW |
dc.title | Characterizing Dna Biobricks to Design Gene Circuit and Program E. Coli | en_US |
dc.type | Plan | en_US |
dc.contributor.department | 國立交通大學生物科技學系(所) | zh_TW |
顯示於類別: | 研究計畫 |