Logic Gates - Emma Garren - Revision history

Emgarren: /* Cellular Logic with Orthogonal Ribosomes. (Rackham and Chin, 2006) */

2007-12-14T02:33:41Z

‎Cellular Logic with Orthogonal Ribosomes. (Rackham and Chin, 2006)

Emgarren: /* Cellular Logic Gates: ''In Vivo'' */

2007-12-14T02:32:39Z

‎Cellular Logic Gates: ''In Vivo''

WikiSysop: /* Logic Gates in Synthetic Biology */

2007-12-12T21:54:53Z

‎Logic Gates in Synthetic Biology

WikiSysop: /* Logic Gates in Synthetic Biology */

2007-12-12T21:54:01Z

‎Logic Gates in Synthetic Biology

WikiSysop: /* Logic Gates in Synthetic Biology */

2007-12-12T21:53:21Z

‎Logic Gates in Synthetic Biology

Emgarren: /* Applications and Future Directions */

2007-12-06T17:21:20Z

‎Applications and Future Directions

Emgarren: /* Synthetic Oscillators and Switches */

2007-12-06T17:20:11Z

‎Synthetic Oscillators and Switches

Emgarren: /* Protein-based Logic Gates */

2007-12-06T17:19:23Z

‎Protein-based Logic Gates

Emgarren: /* Protein-based Logic Gates */

2007-12-06T17:12:24Z

‎Protein-based Logic Gates

Emgarren: /* Protein-based Logic Gates */

2007-12-06T17:12:08Z

‎Protein-based Logic Gates

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 Overview:
-Two-input logic gates were constructed based on the interactions between synthetic O-rRNA and O-mRNA.
+Two-input logic gates were constructed in ''E. coli'' based on the interactions between synthetic O-rRNA and O-mRNA.
 *<b>Input:</b> Orthogonal ribosomes (O-ribosomes), which translate O-mRNA, but do not significantly translate any of the thousands of cellular transcripts bearing cellular RBS sequences.
 *<b>Gate:</b> Orthogonal mRNAs (O-mRNAs), which contain ribosome-binding sequences (RBSs) that do not direct the translation of downstream genes by endogenous ribosomes.

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 =Cellular Logic Gates: ''In Vivo''=
-As stated above, there the cellular environment possesses many characteristics that complicate the implementation of biomolecular logic circuits, such as gene expression noise, mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context.  Some researchers are trying to engineer the "minimal cell," either through top-down or bottom-up approaches, in order to produce a living unit that can perform logical operations without some of these excess confounding factors found in the cells used .  These efforts were recently reviewed by [http://www.nature.com/msb/journal/v2/n1/pdf/msb4100090.pdf Forster and Church (2006)].    However, many efforts at building cellular logic gates have succeeded, both in prokaryotes and eukaryotes, with wide-ranging applications.  Below are summaries of a few examples.
+As stated above, there the cellular environment possesses many characteristics that complicate the implementation of biomolecular logic circuits, such as gene expression noise, mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context.  Some researchers are trying to engineer the "minimal cell," either through top-down or bottom-up approaches, in order to produce a living unit that can perform logical operations without some of these excess confounding factors.  These efforts were recently reviewed by [http://www.nature.com/msb/journal/v2/n1/pdf/msb4100090.pdf Forster and Church (2006)].    However, many efforts at building cellular logic gates have succeeded, both in prokaryotes and eukaryotes, with wide-ranging applications.  Below are summaries of a few examples.
 ==Synthetic Oscillators and Switches==

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 Synthetic biology applies many of the principles of engineering to the field of biology in order to create biological devices which can ultimately be integrated into increasingly complex systems.  These principles include standardization of parts, modularity, abstraction, reliability, predictability, and uniformity (Adrianantoandro ''et al.'', 2006).  The application of engineering principles to biology is complicated by the inability to predict the functions of even simple devices and modules within the cellular environment.  Some of the confounding factors are [[Term paper wiki|gene expression noise]], mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro ''et al.'', 2006).
-While for digital logic, inputs are either on or off (1 or 0), biological logic is sometimes leads to intermediate induction levels (Voigt, 2006).  However, due to their [http://en.wikipedia.org/wiki/Sigmoid_function sigmoid-shaped] dose response curves, gene regulation systems can be considered genetic analog-digital converters.  The signal is either ON or OFF for a wide range of input concentrations, with the system changing between the ON and OFF states in a relatively small concentration window (Kramer et al., 2004).
+While for digital logic, inputs are either on or off (1 or 0), biological logic is sometimes leads to intermediate induction levels (Voigt, 2006).  However, due to their [http://en.wikipedia.org/wiki/Sigmoid_function sigmoid-shaped] dose response curves, gene regulation systems can be considered genetic analog-digital converters.  The signal is either ON or OFF for a wide range of input concentrations, with the system changing between the ON and OFF states in a relatively small concentration window (Kramer ''et al.'', 2004).
 In synthetic biology, logic gates are created by engineering the biochemical reactions that regulate various cellular processes, such as transcription, translation, protein phosphorylation, allosteric regulation, ligand/receptor binding, and enzymatic reactions.  Although the diversity of biochemical reactions can make it difficult to combine different devices, these logic gates can be used to build complex systems with functions that have many practical applications.  [http://gcat.davidson.edu/GcatWiki/index.php/CellularMemory:Mathematical_Models Mathematical modeling] is used to predict the dynamics of the signaling and regulatory networks resulting from the logic gates.

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 =Logic Gates in Synthetic Biology=
-Synthetic biology applies many of the principles of engineering to the field of biology in order to create biological devices which can ultimately be integrated into increasingly complex systems.  These principles include standardization of parts, modularity, abstraction, reliability, predictability, and uniformity (Adrianantoandro ''et al.'', 2006).  The application of engineering principles to biology is complicated by the inability to predict the functions of even simple devices and modules within the cellular environment.  Some of the confounding factors are [[Term paper wiki|gene expression noise]], mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro et al., 2006).
+Synthetic biology applies many of the principles of engineering to the field of biology in order to create biological devices which can ultimately be integrated into increasingly complex systems.  These principles include standardization of parts, modularity, abstraction, reliability, predictability, and uniformity (Adrianantoandro ''et al.'', 2006).  The application of engineering principles to biology is complicated by the inability to predict the functions of even simple devices and modules within the cellular environment.  Some of the confounding factors are [[Term paper wiki|gene expression noise]], mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro ''et al.'', 2006).
 While for digital logic, inputs are either on or off (1 or 0), biological logic is sometimes leads to intermediate induction levels (Voigt, 2006).  However, due to their [http://en.wikipedia.org/wiki/Sigmoid_function sigmoid-shaped] dose response curves, gene regulation systems can be considered genetic analog-digital converters.  The signal is either ON or OFF for a wide range of input concentrations, with the system changing between the ON and OFF states in a relatively small concentration window (Kramer et al., 2004).

@@ Line 14: / Line 14: @@
 =Logic Gates in Synthetic Biology=
-Synthetic biology applies many of the principles of engineering to the field of biology in order to create biological devices which can ultimately be integrated into increasingly complex systems.  These principles include standardization of parts, modularity, abstraction, reliability, predictability, and uniformity (Adrianantoandro et al., 2006).  The application of engineering principles to biology is complicated by the inability to predict the functions of even simple devices and modules within the cellular environment.  Some of the confounding factors are [[Term paper wiki|gene expression noise]], mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro et al., 2006).
+Synthetic biology applies many of the principles of engineering to the field of biology in order to create biological devices which can ultimately be integrated into increasingly complex systems.  These principles include standardization of parts, modularity, abstraction, reliability, predictability, and uniformity (Adrianantoandro ''et al.'', 2006).  The application of engineering principles to biology is complicated by the inability to predict the functions of even simple devices and modules within the cellular environment.  Some of the confounding factors are [[Term paper wiki|gene expression noise]], mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro et al., 2006).
 While for digital logic, inputs are either on or off (1 or 0), biological logic is sometimes leads to intermediate induction levels (Voigt, 2006).  However, due to their [http://en.wikipedia.org/wiki/Sigmoid_function sigmoid-shaped] dose response curves, gene regulation systems can be considered genetic analog-digital converters.  The signal is either ON or OFF for a wide range of input concentrations, with the system changing between the ON and OFF states in a relatively small concentration window (Kramer et al., 2004).

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 *Nanotechnology
 *Industrial Fermentation
-*Metabolic engineering: increasingly complex synthetic gene circuits might be used to engineer and optimize novel metabolic pathways.
+*Metabolic engineering:
-*[[Medical Applications of Synthetic Biology - Samantha Simpson|Medicine]]
+**increasingly complex synthetic gene circuits might be used to engineer and optimize novel metabolic pathways.
 **Bacteria to deliver cancer treatment: the integration of multiple inputs can help bacteria sense and respond to increasingly specific environments, such as that of a tumor in the human body.
 **Pharmaceuticals: produced through metabolic engineering; "smart" drug delivery.

← Older revision		Revision as of 17:20, 6 December 2007
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	[[Image:design_fig_1d.gif]]		[[Image:design_fig_1d.gif]]
		+
	(Image from Figure 1 of Drubin et al., 2007. Permission pending.)		(Image from Figure 1 of Drubin et al., 2007. Permission pending.)

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 Signaling Proteins:
-*<b>Engineering synthetic signaling proteins with ultrasensitive input/output control. (Dueber et al., 2007)</b>  Summary: Many eukaryotic signaling proteins have natural, modular "input" and "output" domains:  the "inputs" participate in steric or conformational autoinhibitory reactions, and the "outputs" are catalytically, constitutively active domains.  Simple synthetic switch functions can be engineered by swapping the regulatory and catalytic domains.  This paper describes the engineering of "ultrasensitive switches" for use in more complex regulatory networks, by combining multiple identical modular autoinhibitory domains that function [http://en.wikipedia.org/wiki/Cooperativity cooperatively].  The authors used mathematical models to simulate the behavior of these multivalent domain switches and explore the effect of autoinhibitory interaction number and affinity: an external input ligand alters the population distribution of active vs. inactive enzymes, where individual states are "fully repressed in the presence of any intramolecular interactions and fully active only in the absence of all intramolecular interactions" (661).
+*<b>Engineering synthetic signaling proteins with ultrasensitive input/output control. (Dueber et al., 2007)</b>  Summary: Many eukaryotic signaling proteins have natural, modular "input" and "output" domains:  the "inputs" participate in steric or conformational autoinhibitory reactions, and the "outputs" are catalytically, constitutively active domains.  Simple synthetic switch functions can be engineered by swapping the regulatory and catalytic domains.  This paper describes the engineering of "ultrasensitive switches" for use in more complex regulatory networks, by combining multiple identical modular autoinhibitory domains that function [http://en.wikipedia.org/wiki/Cooperativity cooperatively].  Mathematical models are used to simulate the behavior of these multivalent domain switches and explore the effect of autoinhibitory interaction number and affinity: an external input ligand alters the population distribution of active vs. inactive enzymes, where individual states are "fully repressed in the presence of any intramolecular interactions and fully active only in the absence of all intramolecular interactions" (661).  The predictions from the models are tested using synthetic switches built by linking the catalytic output domain of the protein N-WASP to novel peptide input, demonstrating that it is possible to engineer nonlinear switches based on the cooperativity of simple autoinhibitory components.  Other complex switches, such as ones that integrate three input signals, have also been built using this approach.
 ==Deoxyribozyme-based Logic Gates==