Programmable Cells: Engineer Turns Bacteria Into Living Computers
04/27/05 -- In a step toward making living cells function as if they were tiny computers, engineers at Princeton have programmed bacteria to communicate with each other and produce color-coded patterns.
The feat, accomplished in a biology lab within the Department of Electrical Engineering, represents an important proof-of-principle in an emerging field known as "synthetic biology," which aims to harness living cells as workhorses that detect hazards, build structures or repair tissues and organs within the body.
"We are really moving beyond the ability to program individual cells to programming a large collection -- millions or billions -- of cells to do interesting things," said Ron Weiss, an assistant professor of electrical engineering and molecular biology.
Collaborating with researchers at the California Institute of Technology, Weiss and graduate student Subhayu Basu programmed E. coli bacteria to emit red or green fluorescent light in response to a signal emitted from another set of E. coli. In one experiment, the cells glowed green when they sensed a higher concentration of the signal chemical and red when they sensed a lower concentration. In a Petri dish, they formed a bull's-eye pattern -- a green circle inside a red one -- surrounding the sender cells.
In addition to demonstrating that the genetic programming techniques work, this sensing system could be useful for the detection of chemicals or organisms in laboratory tests. "The bull's-eye could tell you: This is where the anthrax is," said Weiss.
The researchers published their results in the April 28 issue of Nature. In addition to Weiss and Basu, authors of the paper are postdoctoral researcher Yoram Gerchman at Princeton and professor of chemical engineering Frances Arnold and graduate student Cynthia Collins at Caltech. It was funded by a grant from the U.S. Defense Advanced Research Projects Agency.
In previous work, including a paper published March 8 in the Proceedings of the National Academy of Sciences along with Sara Hooshangi and Stephan Thiberge, Weiss showed the feasibility of inserting engineered pieces of DNA into cells to make them behave in the same manner as digital circuits. The cells, for example, could be made to perform basic mathematical logic and produce crisp, reliable readouts that are more commonly associated with silicon chips than biological organisms. The new paper applies similar techniques to a large population of cells.
"Here we're showing an integrated package where the cells have an ability to send messages and other cells have the ability to act on these messages," said Weiss.
The creation of patterns, such as the bull's-eye effect, is a key step in one of Weiss' eventual goals, which is to have the cells secrete materials that build physical devices such as antennas or transmitters in places that are hard for humans to reach. Programmed cells also could be used to control the repair or construction of tissues within the body, possibly guiding stem cells to the locations where they are needed for the growth of new nerve or bone cells in a process Weiss called "programmed tissue engineering."
Even the early step of creating patterns in a Petri dish, however, may be useful as a tool for other scientists, particularly developmental biologists who are trying to understand how the cells of an embryo arrange themselves into patterns that become the various body parts of a mature organism. In fruit fly embryos, for example, the first cells are thought to differentiate into the head, abdomen and other parts based on the concentration of chemical signals that are emitted from the ends of the embryo.
In addition to conducting laboratory experiments, Weiss and colleagues are creating computer models of their engineered systems, which allow them to study how small modifications would affect the ultimate behavior of the organisms. So far, said Weiss, the experimental results have matched the computer models fairly closely, but the goal is to have a mathematically exact description of how each component works.
"One of the nice things about synthetic biology is that because we built the network from scratch, we should be able to model all the important details," he said. At some point in the future, he said, scientists will be able to choose a behavior they want from cells, and a computer program will create a genetic circuit to accomplish the task. "Then we can do an experiment to see if the community of cells is behaving as we desire. That is going to have a tremendous number of applications."
Source: Princeton University
据生物网4月27日消息，美国普林斯顿大学的研究人员使细胞相互“交流”并产生彩色编码样式。这一研究代表了“合成生物学”这一新兴领域处于原理论证阶段。合成生物学旨在利用活体细胞来探测人体内的危险物质、修补受损组织和器官。
电子工程学和分子生物学助理教授Ron Weiss与加州理工学院的研究人员合作，使E. coli细菌在另一组E. coli细菌发出信号的刺激下产生红或绿的荧光。当E. coli细菌感觉到较高浓度的化学信号时，细胞发出绿光；若浓度较低时，则发出红光。在皮氏培养皿中，研究人员发现细胞呈靶形（中间一个红的，外面一圈绿的）。除了可以证明基因编码的工作机制外，这一感应体系还能用于实验室检测化学物质或有机体。
这一研究得到美国国防部高级研究计划署的资助，研究成果发表于2005年4月28日的《自然》杂志上。
先前的研究中，Weiss说明了将DNA插入细胞使其以同一方式运作的可行性。比如，细胞可以按照基本的数理逻辑运作，这与生物体相比更接近于硅片的模式。现在，研究人员将相同的技术运用于大量的细胞中。Weiss说：“我们在做的就是要显示细胞发出信息的能力，和其他细胞对信息做出回应的能力。”
靶心效应的产生对研究人员来说是达到最终目标的关键一步。细胞还可被用来控制人体内受损组织的修复，将干细胞引导到需要生长新的神经细胞的地方。
皮氏培养皿中的发现对其他科学家可能有用，特别是那些试图了解胚胎细胞如何成为成熟生物体不同身体部分的生物学家们。
Weiss及其同事们正将他们的研究成果制成计算机模型，这样方便他们研究小的修改是如何影响生物体的最终表现。到目前为止，实验结果与计算机模型非常吻合，但最终目标是精确描述各个组成的运作模式。
将来也许科学家可以随意选择一种他们想要的细胞行为，然后计算机程序将制成基因电路图来帮助完成任务。
