USTC/Introduction

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Logic Artificial Biological Circuit (ABC) and logic Integrated Circuit (IC) are both composed of "components" and "wires". Though people have been enjoying the advantages of Ultra Large Scale IC (ULSI), we still cannot implement in real experiments a somewhat large-scale logic ABC with several levels of logic gates in it.
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[[Image:USTC_Biologic vs Electronic.png|thumb|right|Comparison of electronic transistor with DNA helix.]]
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Our project is to provide a new method for building up a fully extensible logic ABC. For some biological convenience, we are going to produce such biological logic gates as NAND, NOR, NOT which are exactly the basis for modern logic IC. More importantly, several factors influence the scale of ABC and IC, such as, the size and power of the components, the interference between wires, and standardization of intercommunication. Cis-acting components in ABC may present a smaller scale and power request than trans-acting ones, while the other two factors can be improved by novelly-designed and calibrated wires. We are also going to demonstrate an ABC made by these biological logic gates and wires.
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It is charming for biology scientists to implement a computer in biological organisms. Primarily, logic circuits made with biological materials can work <i>in vitro</i> [1]. More to the point, attempts to carry out unique logic gates <i>in vivo</i> have been reported [2]. Here, our team has been trying to work out a systematic method to realize an extensible logical circuit <i>in vivo</i>.
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==NOR Gate==
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As the basic elements of the logic circuits, AND, OR and NOT (or NAND, NOR and NOT) gates should be implemented in the first instance. Transcriptional regulation, which is widely found in biological organism, can be considered as a kind of switch. It serves as the basis of the logic gates <i>in vivo</i>. A negative transcriptional regulation is utilized as a NOT gate. The NOR and NAND gates are realized by installing two operator at the proper distance. All the gates are made on a 60~200-bp DNA fragments in this way.
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[[Image:ustc_nor gate.jpg|thumb|256px]]
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[[Image:USTC_TruthTableNOR.png|203px]]
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To transmit signals between the gates is more complex <i>in vivo</i> than to do so in vitro. The signal messengers should be specific enough to avoid interference among them. Also, their life expectancy should be long enough to finish their work.  Proteins are employed here to be the messengers. To possess enough binding specificity with DNA, proteins are screened with computational protein design and directed evolution. Highly qualified wires are thus obtained.
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The NOR gate is a digital logic gate that implements logical NOR - it behaves according to the truth table to the left. A HIGH output (1) results if both the inputs to the gate are LOW (0). If one or both input is HIGH (1), a LOW output (0) results. In other words, it produces a value of false if and only if at least one operand is true. (from wikipedia)
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Furthermore, by means of assembling all our parts, a demonstration system will be made to drive the integrated system to work <i>in vivo</i>.
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The draft to the right shows the NOR Gate we have determined ourselves to experimentally implement. It is an extract made from our weekly group meeting. As is shown in the draft, the RNA Polymerase cannot bind to the its target site.
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<TODO>
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1. Georg Seelig, David Soloveichik, David Yu Zhang, Erik Winfree, 'Enzyme-Free Nucleic Acid Logic Circuits', <i>Science</i> Vol. 314. no. 5805, pp. 1585 - 1588 (2006)
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==NAND Gate==
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2. Yohei Yokobayashi, Ron Weiss, and Frances H. Arnold, 'Directed evolution of a genetic circuit', <i>PNAS</i> (2002) vol 99 no 26 16587–16591
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[[Image:ustc_nand gate.jpg|thumb|256px]]
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[[Image:USTC_TruthTableNAND.png|203px]]
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The NAND operation is a logical operation on two logical values, typically the values of two propositions, that produces a value of false if and only if both of its operands are true. In other words, it produces a value of true if and only if at least one of its operands is false. A LOW output results only if both the inputs to the gate are HIGH. If one or both inputs are LOW, a HIGH output results.(from wikipedia)
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The draft to the right shows the NAND Gate we are destined to physically realize. It is also an extract made from an ordinary group meeting.
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<TODO>
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==NOT Gate==
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[[Image:ustc_not gate.jpg|thumb|256px]]
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[[Image:USTC_TruthTableNOT.png|150px]]
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The NOT gate is a digital logic gate that implements logical negation. It behaves according to the truth table to the left. A HIGH output (1) results if the inputs is LOW (0). If the input is HIGH (1), a LOW output (0) results. (from wikipedia)
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The draft to the right shows the NOT gate we plan to complete in the project.
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The existence of repressor A fulfils the function of a simple NOT Gate. RNA Polymerase will not bind to the according RBS when the repressor has already bounds an operator. Not until the operator is relieved from the repressor will the RNA Polymerase come to work again.
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Latest revision as of 03:06, 27 October 2007

Comparison of electronic transistor with DNA helix.

It is charming for biology scientists to implement a computer in biological organisms. Primarily, logic circuits made with biological materials can work in vitro [1]. More to the point, attempts to carry out unique logic gates in vivo have been reported [2]. Here, our team has been trying to work out a systematic method to realize an extensible logical circuit in vivo.

As the basic elements of the logic circuits, AND, OR and NOT (or NAND, NOR and NOT) gates should be implemented in the first instance. Transcriptional regulation, which is widely found in biological organism, can be considered as a kind of switch. It serves as the basis of the logic gates in vivo. A negative transcriptional regulation is utilized as a NOT gate. The NOR and NAND gates are realized by installing two operator at the proper distance. All the gates are made on a 60~200-bp DNA fragments in this way.

To transmit signals between the gates is more complex in vivo than to do so in vitro. The signal messengers should be specific enough to avoid interference among them. Also, their life expectancy should be long enough to finish their work. Proteins are employed here to be the messengers. To possess enough binding specificity with DNA, proteins are screened with computational protein design and directed evolution. Highly qualified wires are thus obtained.

Furthermore, by means of assembling all our parts, a demonstration system will be made to drive the integrated system to work in vivo.


1. Georg Seelig, David Soloveichik, David Yu Zhang, Erik Winfree, 'Enzyme-Free Nucleic Acid Logic Circuits', Science Vol. 314. no. 5805, pp. 1585 - 1588 (2006)

2. Yohei Yokobayashi, Ron Weiss, and Frances H. Arnold, 'Directed evolution of a genetic circuit', PNAS (2002) vol 99 no 26 16587–16591