A Switch for Synthetic Biology Based on Feature Density

基于特征密度的合成生物学开关

• 批准号: 1160005
• 负责人: William Bentley
• 金额: $ 32.76万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1160005&HistoricalAwards=false
• 关键词: Switch; Synthetic; Biology; Based; Feature

1160005/ BentleyThe most successful examples of the new field of synthetic biology have come from imparting new capabilities into microorganisms for the production of unnatural products or products not typically made by those cells. Entire genomes are rearranged - at times to ensure the effects of product overproduction are tolerated by the producing cells (e.g., biofuels can inhibit producing cell growth). Generally, all cells act identically and optimally. In few examples are the cells themselves the "product" of synthetic biology. In an alternative view, individual cells can carry out high level functions. They can even direct other groups of cells. The motivation of this work is to exploit the sensing and computational power of bacteria. More specifically, a new biological switch that will expand the reach of synthetic biology is envisioned - a switch that is activated by cells that recognize "features" on nearby surfaces. Notably, one could build a bacterium that surveys the area-based density of a feature on the surface below. A "go"::"no-go" decision is made and implemented by the "smart" bacterium. One potential application would reengineer bacteria to recognize a cancerous cell from a healthy cell. The cancer cells have more epidermal growth factor receptor (EGFR) on their surfaces than healthy cells. While nanoparticle-based drug delivery brings drugs to any cell displaying the receptor, this new methodology would instead ask the drug carrying bacteria to decide whether the cell is truly cancerous, based on the surface density of the EGFR. The bacteria could then reprogram themselves to synthesize the drug and deliver it. This autonomous smart mode of drug delivery is unprecedented.

1160005/Bentley合成生物学新领域最成功的例子来自于赋予微生物新的能力，以生产非天然产物或通常不由这些细胞生产的产物。整个基因组被重排-有时以确保生产细胞耐受产物过量生产的影响（例如，生物燃料可抑制生产细胞生长）。一般来说，所有的细胞都以相同的方式和最佳的方式发挥作用。 在少数例子中，细胞本身就是合成生物学的“产物”。在另一种观点中，单个细胞可以执行高级功能。它们甚至可以指挥其他细胞群。这项工作的动机是利用细菌的传感和计算能力。更具体地说，设想了一种新的生物开关，它将扩大合成生物学的范围--一种由识别附近表面“特征”的细胞激活的开关。值得注意的是，人们可以建立一种细菌，它可以测量下面表面上某个特征的面积密度。“去”：“不去”的决定由“聪明”的细菌做出并执行。一个潜在的应用是重新设计细菌，以识别健康细胞中的癌细胞。癌细胞表面比健康细胞有更多的表皮生长因子受体（EGFR）。虽然基于纳米颗粒的药物递送将药物带到显示受体的任何细胞，但这种新方法将要求携带药物的细菌根据EGFR的表面密度来决定细胞是否真正癌变。然后，细菌可以重新编程自己来合成药物并将其输送出去。这种自主智能的药物输送模式是前所未有的。