Digital Microfluidic Artificial Golgi for Glycan Synthesis

用于聚糖合成的数字微流控人工高尔基体

• 批准号: 0730817
• 负责人: Jonathan Dordick
• 金额: $ 30万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2011-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0730817&HistoricalAwards=false
• 关键词: Digital; Microfluidic; Artificial; Golgi; Glycan; Digital; Microfluidic; Artificial; Golgi; Glycan

Digital Microfluidic Artificial Golgi for Glycan SynthesisJonathan DordickRensselaer Polytechnic InstituteCBET-0730817Glycosylation, the most important posttranslational modification of proteins, occurs in the Golgi organelle. The complexity of glycosylation has hindered fundamental understanding of biosynthesis and has made controlled synthesis of essential therapeutic agents difficult and expensive. Therefore, there is a compelling need to develop a fundamental understanding of glycan biosynthesis within the Golgi, which will lead to the development of artificial routes to the synthesis, modification, and ultimately large-scale synthesis of glycans and glycoproteins. The goal of this research is to perform the controlled biocatalytic synthesis of heparan sulfate/heparin via digital microfluidic systems (DMFS), which are a new class of lab-on-chip systems that manipulate discrete droplets of chemicals on an array of electrodes. Intellectual Merit: This research will lead to a fundamental understanding of glycosylation in the Golgi, and mimic these processes by examining precisely controlled variations of spatial and temporal parameters in enzyme catalysis. As a model, in-vitro synthesis of heparan sulfate/heparin will represent the first demonstration of an artificial Golgi that may be of utility in the synthesis of a wide variety of therapeutic glycoproteins. Precise control algorithms will be developed to enable efficient glycosylation and will establish a comprehensive framework to design fluid movement, retention, and separation, much like in the Golgi organelle. Broader Impacts: Results will be integrated into graduate courses on Synthetic Biology and Robot Motion Planning. An even broader impact will result from integrating this project into ongoing efforts at RPI in the development of the MoleculariumTM, a combination planetarium and virtual space ride that takes the audience into the world of atoms and molecules. Broader societal outcomes of the proposed research include the development of the next generation of glycan-containing drugs and the design of low-cost, portable lab-on-a-chip systems capable of rapid automated biochemical analyses for point-of-care testing, research and drug discovery.

用于聚糖合成的数字微流体人造高尔基，dordickrensselaer理工学院-0730817-糖基化是蛋白质的最重要的翻译后修饰，是Golgi Organle中的最重要的蛋白质。糖基化的复杂性妨碍了对生物合成的基本理解，并使得对基本治疗剂的控制综合变得困难和昂贵。因此，迫切需要对高尔基体内的聚糖生物合成产生基本的理解，这将导致人为的途径发展，以促进合成，修饰，并最终大规模合成聚糖和糖蛋白。这项研究的目的是通过数字微流体系统（DMFS）执行对乙par硫酸盐/肝素的受控生物催化合成，该系统是一类新的实验室芯片系统，可在一系列电极上操纵分散的化学物质。智力优点：这项研究将导致对高尔基体中糖基化的基本理解，并通过检查酶催化中空间和时间参数的精确控制变化来模仿这些过程。作为一个模型，硫酸乙酰肝素/肝素的体外合成将代表人造高尔基体的首次证明，该演示可能是在综合多种治疗性糖蛋白的合成中实用的。将开发精确的控制算法以实现有效的糖基化，并将建立一个全面的框架来设计流体运动，保留和分离，就像在高尔基体细胞器中一样。更广泛的影响：结果将纳入有关合成生物学和机器人运动计划的研究生课程中。将该项目集成到RPI的持续努力中，在MoleculariumTM的开发过程中，这是一个更广泛的影响，这是一个组合的天文馆和虚拟太空骑行，它将观众带入原子和分子世界。拟议研究的更广泛的社会结果包括开发下一代含聚糖药物的药物以及能够快速自动化的生物化学分析的低成本，可移植的实验室芯片系统，以进行护理点测试，研究和药物发现。