A Switch for Synthetic Biology Based on Feature Density

1160005/Bentley合成生物学新领域最成功的例子是赋予微生物新的能力，以生产非天然产品或通常不是由这些细胞制造的产品。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过度生产的影响(例如，生物燃料可以抑制生产细胞的生长)。一般说来，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。他们甚至可以引导其他细胞群。这项工作的动机是开发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，它将扩大合成生物学的研究范围--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来调查下面表面上某个地物的面积密度。“去”：“不去”的决定是由“聪明”的细菌做出并执行的。一个潜在的应用是重新设计细菌，以识别癌细胞和健康细胞。癌细胞比健康细胞表面有更多的表皮生长因子受体(EGFR)。虽然基于纳米颗粒的药物输送将药物带到任何显示受体的细胞，但这种新的方法将转而要求携带药物的细菌根据EGFR的表面密度来判断细胞是否真的是癌细胞。然后，细菌可以对自己进行重新编程，以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史无前例的。

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.