CAREER: Molecular Systems Bioengineering

职业：分子系统生物工程

• 批准号: 0238617
• 负责人: Charles Roth
• 金额: $ 40万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0238617&HistoricalAwards=false
• 关键词: CAREER; Molecular; Systems; Bioengineering

The overall objective of the proposed research is to develop tools of Molecular Systems Bioengineering (MSB) and apply them to understand and control gene regulatory events involved in hepatocyte (primary liver cell) differentiation. In the first stage of the project, individual binding sites on the albumin gene promoter will be assessed for liver-enriched transcription factor binding affinity and their ability to effect transcription of the albumin gene. In particular, context-dependent effects such as cooperativity and competition among binding sites will be evaluated quantitatively. Second, a molecular systems model will be developed to describe the gene network of regulatory interactions among liver-enriched transcription factor genes and corresponding proteins. Information on cooperativity and competition will be obtained from the experiments in the first stage, and the effect of genetic perturbations will be simulated. In the third stage, perturbations predicted to be fruitful will be effected using antisense oligonucleotides. Genes predicted to be most inhibitory to albumin transcription will be inhibited and the effects evaluated at the level of the gene target, albumin production and complementary hepatocyte differentiated functions. Concurrently, initiatives will be undertaken to create an educational path in Molecular Systems Bioengineering at Rutgers University. An undergraduate track in MSB will be developed in the Department of Biomedical Engineering, and interactive tutorials will be developed in the undergraduate core classes, which will be refined for use as translational materials in introducing high school student and Rutgers freshmen to opportunities in MSB.

拟议研究的总体目标是开发分子系统生物工程（MSB）的工具，并将其应用于肝细胞（原发性肝细胞）分化涉及的基因调节事件。 在项目的第一阶段中，将评估白蛋白基因启动子上的单个结合位点的肝脏含有转录因子结合亲和力及其影响白蛋白基因转录的能力。 特别是，将对上下文依赖性效应，例如在结合位点之间的合作性和竞争性竞争，将进行定量评估。 其次，将开发一个分子系统模型来描述富含肝脏的转录因子基因和相应蛋白质之间调节性相互作用的基因网络。 第一阶段的实验将获得有关协作性和竞争的信息，并将模拟遗传扰动的效果。 在第三阶段，预计将使用反义寡核苷酸实现果实。 预计将最抑制白蛋白转录的基因将受到抑制，并且在基因靶标，白蛋白产生和互补肝细胞分化功能的水平上评估的效果。 同时，将采取行动在罗格斯大学（Rutgers University）在分子系统生物工程中建立教育道路。 生物医学工程系将开发MSB的本科轨道，并将在本科核心课程中开发互动教程，该教程将在向高中生和Rutgers Freshmen引入MSB的机会时，将其用作转化材料。