Logic Gates - Emma Garren

Logic Gates in Synthetic Biology

Background: Logic Gates and Truth Tables

A logic gate, the building block for digital circuits, is a computing unit that performs a logical operation on one or more inputs and produces a single output. Gates are identified by their function, and each type of logic gate can be represented with a distinctive symbol. The inputs are represented with short line segments to the left of the shape, and the output is represented by a short line segment to the right of the shape. A small circle on the right indicates that the output of the logical operation is inverted. Here are some examples:

A truth table is a useful way to describe the behavior or function of a logic gate. A "1" is used for "true" or a positive input, and a "0" is used for "false" or a negative input.

Logic Gates in Synthetic Biology

Engineering Principles

1. Standardization of parts
2. Component abstraction
3. Separation of system design from system fabrication

Biomolecular logic gates can be used as "parts" in the design of synthetic gene circuits.

Challenges from the cellular environment: Synthetic biology research is hindered by the inability to predict the functions of even simple devices and modules within the cellular environment. Some of the confounding factors are gene expression noise, mutation, cell death, undefined and changing extracellular environments, and interactions with the cellular context (Adrianantoandro et al., 2006).

Significance of modularity... High level of modularity in the regulatory elements of eukaryotic systems (Heinemann and Panke, 2006) - allows for integration of more and more signals into determining a single output or cellular function.

Biomolecular Logic Gates: In Vitro

In vitro studies have been used to design combinations of molecules that have emergent properties related to information processing--molecular computing devices. Both the inputs and outputs consist of molecular species, with the output being a biologically active molecule. The extent to which these devices will be used with the cellular context is unclear--however, they are bound to inspire new directions for research in synthetic biology, and have potential applications in biochemical sensing, pathway engineering, and medical diagnosis and treatment.

Computing with Enzymes

Baron et al.

Ribozyme-Based Logic Gates

Stojanovic and Stephanovic

Synthetic Signaling Proteins

Dueber et al. - engineering synthetic signaling proteins with ultrasensitive input/output control.

DNA Self-Assembly

Yan et al.

Seelig et. al.

DNA-Based Logic Gates

Frezza et al.

Yoshida and Yokobayashi

Miyoshi et al.

Other

An autonomous molecular computer for logical control of gene expression. (Benenson et al., 2004) This paper describes an in vitro system that recognizes a specific combination of mRNA levels as its inputs, and performs a logical operation that results in the production of a molecule that can affect gene expression. Because the mRNA levels have been designed to mimic a simplistic version of gene expression modeling cancer, and the output is a drug-like ssDNA with known anticancer activity, the molecular computer is analogous to "a computational version of 'diagnosis'" (424).

Cellular Logic Gates: In Vivo

Various types of molecular logic gates allow for the design of synthetic gene circuits... Modularity...

Oscillators and Bistable Switches

Elowitz and Leibler Collins - toggle switch

Environmental Signal Integration

Modular AND gate

Artificial Cellular Communication Networks

Quorum-sensing as input for logical operation

Circuits engineered in the context of multicellular systems... Two different cell types in a bacterial population (Basu et al. 2004 and 2005, described in "Designing biological systems" review paper)

Logic Gates in Mammalian Cells

Fusseneger

Applications and Future Directions

Synthetic gene circuits - use multiple simple input-output logic systems to design and build more complex circuits.

Medical applications - Cancer treatment - Increase specificity with which bacteria can sense an environment by combining multiple environmental inputs in logic gates. Autonomous biomolecular computing devices - use for molecular-level diagnostics and treatment

References

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