A Switch for Synthetic Biology Based on Feature Density

[160005]本特利合成生物学新领域中最成功的例子来自于赋予微生物生产非天然产品或通常不是由这些细胞生产的产品的新能力。整个基因组被重新排列——有时是为了确保生产细胞能够容忍产品生产过剩的影响（例如，生物燃料可以抑制生产细胞的生长）。一般来说，所有细胞的行为都是相同的和最优的。在少数例子中，细胞本身是合成生物学的“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感知和计算能力。更具体地说，人们设想了一种新的生物开关，它将扩展合成生物学的范围——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，人们可以构建一种细菌，它可以测量下面表面上一个特征的基于面积的密度。“聪明”的细菌做出“去”：“不去”的决定并执行。一个潜在的应用是重组细菌，使其从健康细胞中识别癌细胞。癌细胞表面的表皮生长因子受体（EGFR）比健康细胞多。虽然基于纳米颗粒的药物输送可以将药物输送到任何显示受体的细胞中，但这种新的方法将要求携带药物的细菌根据表皮生长因子受体的表面密度来决定细胞是否真的癌变。然后，细菌可以对自己进行重新编程，合成药物并将其输送出去。这种自主智能给药模式是前所未有的。

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.