@ARTICLE{andrianantoandro06,
AUTHOR = {Ernesto Andrianantoandro and Subhayu Basu and David
K Karig and Ron Weiss},
TITLE = {Synthetic biology: new engineering rules for an
emerging discipline},
JOURNAL = {Molecular Systems Biology},
YEAR = 2006,
VOLUME = 2,
NUMBER = 1,
DOI = {doi:10.1038/msb4100073},
ABSTRACT = {Synthetic biologists engineer complex artificial
biological systems to investigate natural biological
phenomena and for a variety of applications. We
outline the basic features of synthetic biology as a
new engineering discipline, covering examples from
the latest literature and reflecting on the features
that make it unique among all other existing
engineering fields. We discuss methods for designing
and constructing engineered cells with novel
functions in a framework of an abstract hierarchy of
biological devices, modules, cells, and
multicellular systems. The classical engineering
strategies of standardization, decoupling, and
abstraction will have to be extended to take into
account the inherent characteristics of biological
devices and modules. To achieve predictability and
reliability, strategies for engineering biology must
include the notion of cellular context in the
functional definition of devices and modules, use
rational redesign and directed evolution for system
optimization, and focus on accomplishing tasks using
cell populations rather than individual cells. The
discussion brings to light issues at the heart of
designing complex living systems and provides a
trajectory for future development.}
}
@ARTICLE{atkinson03,
AUTHOR = {Mariette R. Atkinson and Michael A. Savageau and
Jesse T. Myers and Alexander J. Ninfa},
TITLE = {Development of Genetic Circuitry Exhibiting Toggle
Switch or Oscillatory Behavior in {{\em Escherichia
coli}}},
JOURNAL = {Cell},
YEAR = 2003,
VOLUME = 113,
NUMBER = 5,
PAGES = {597--607},
MONTH = MAY,
DOI = {doi:10.1016/S0092-8674(03)00346-5},
ABSTRACT = {Analysis of the system design principles of
signaling systems requires model systems where all
components and regulatory interactions are
known. Components of the Lac and Ntr systems were
used to construct genetic circuits that display
toggle switch or oscillatory behavior. Both devices
contain an ``activator module'' consisting of a
modified glnA promoter with lac operators, driving
the expression of the activator, NRI. Since NRI
activates the glnA promoter, this creates an
autoactivated circuit repressible by LacI. The
oscillator contains a ``repressor module''
consisting of the NRI-activated glnK promoter
driving LacI expression. This circuitry produced
synchronous damped oscillations in turbidostat
cultures, with periods much longer than the cell
cycle. For the toggle switch, LacI was provided
constitutively; the level of active repressor was
controlled by using a lacY mutant and varying the
concentration of IPTG. This circuitry provided
nearly discontinuous expression of activator. },
PMID = 12787501
}
@ARTICLE{ball04,
AUTHOR = {Philip Ball},
TITLE = {Synthetic biology: Starting from scratch},
JOURNAL = {Nature},
YEAR = 2004,
VOLUME = 431,
NUMBER = 7009,
PAGES = {624--626},
MONTH = OCT,
DOI = {doi:10.1038/431624a},
ABSTRACT = {Genetic engineering is old hat. Biologists are now
synthesizing genomes, altering the genetic code and
contemplating new life forms. Is it time to think
about the risks? Philip Ball asks the experts.},
PMID = 15470399
}
@ARTICLE{basu04,
AUTHOR = {Subhayu Basu and Rishabh Mehreja and Stephan
Thiberge and Ming-Tang Chen and Ron Weiss },
TITLE = {Spatiotemporal control of gene expression with
pulse-generating networks},
JOURNAL = {Proc. Natl. Acad. Sci. USA},
YEAR = 2004,
VOLUME = 101,
NUMBER = 17,
PAGES = {6355--6360},
MONTH = APR,
DOI = {doi:10.1073/pnas.0307571101},
ABSTRACT = {One of the important challenges in the emerging
field of synthetic biology is designing artificial
networks that achieve coordinated behavior in cell
communities. Here we present a synthetic
multicellular bacterial system where receiver cells
exhibit transient gene expression in response to a
long-lasting signal from neighboring sender
cells. The engineered sender cells synthesize an
inducer, an acyl-homoserine lactone (AHL), which
freely diffuses to spatially proximate receiver
cells. The receiver cells contain a pulse-generator
circuit that incorporates a feed-forward regulatory
motif. The circuit responds to a long-lasting
increase in the level of AHL by transiently
activating, and then repressing, the expression of a
GFP. Based on simulation models, we engineered
variants of the pulse-generator circuit that exhibit
different quantitative responses such as increased
duration and intensity of the pulse. As shown by our
models and experiments, the maximum amplitude and
timing of the pulse depend not only on the final
inducer concentration, but also on its rate of
increase. The ability to differentiate between
various rates of increase in inducer concentrations
affords the system a unique spatiotemporal behavior
for cells grown on solid media. Specifically,
receiver cells can respond to communication from
nearby sender cells while completely ignoring
communication from senders cells further away,
despite the fact that AHL concentrations eventually
reach high levels everywhere. Because of the
resemblance to naturally occurring feed-forward
motifs, the pulse generator can serve as a model to
improve our understanding of such systems.},
PMID = 15096621
}
@ARTICLE{benner05,
AUTHOR = {Steven A. Benner & A. Michael Sismour},
TITLE = {Synthetic biology},
JOURNAL = {Nature Reviews Genetics},
YEAR = 2005,
VOLUME = 6,
PAGES = {533--543},
DOI = {doi:10.1038/nrg1637},
ABSTRACT = {Synthetic biologists come in two broad classes. One
uses unnatural molecules to reproduce emergent
behaviours from natural biology, with the goal of
creating artificial life. The other seeks
interchangeable parts from natural biology to
assemble into systems that function
unnaturally. Either way, a synthetic goal forces
scientists to cross uncharted ground to encounter
and solve problems that are not easily encountered
through analysis. This drives the emergence of new
paradigms in ways that analysis cannot easily
do. Synthetic biology has generated diagnostic tools
that improve the care of patients with infectious
diseases, as well as devices that oscillate, creep
and play tic-tac-toe. },
PMID = 15995697
}
@ARTICLE{brent04,
AUTHOR = {Roger Brent},
TITLE = {A partnership between biology and engineering},
JOURNAL = {Nature Biotechnology},
YEAR = 2004,
VOLUME = 22,
NUMBER = 10,
PAGES = {1211--1214},
MONTH = OCT,
DOI = {doi:10.1038/nbt1004-1211},
ABSTRACT = {This article explores the potentially beneficial
outcomes of a partnership between systems biology
and synthetic biology. This assessment is a
challenge due to the vague definition and
unrealistic claims made for systems biology, as well
as by the lack of an explicitly stated distinction
between synthetic biology and the engineering of
biological systems practiced since the development
of recombinant DNA. Here, I suggest that one might
be able to add meaning to the concept of systems
biology by remembering older conceptions of
experimental systems. In biology, the original word
used for the study of system function is
physiology. It may be possible in the near term to
understand the quantitative physiology of certain
intracellular systems. I then try to determine the
distinguishing attributes of synthetic biology. Any
body of theory and experimental capability that
enables quantitative prediction of a system's
behavior will be applicable to synthetic biology in
that it will enable prediction of the behavior of
human-designed biological artifacts before those are
instantiated in DNA code. If the practitioners are
honest with one another about the limits of their
abilities, this intersection of science and
engineering can spur the development of both.},
PMID = 15470452
}
@ARTICLE{chin06,
AUTHOR = {Jason W. Chin},
TITLE = { Modular approaches to expanding the functions of
living matter},
JOURNAL = {Nature Chemical Biology},
YEAR = 2006,
VOLUME = 2,
NUMBER = 6,
PAGES = {304--311},
MONTH = JUN,
DOI = {doi:10.1038/nchembio789},
ABSTRACT = {The synthesis of increasingly complex unnatural
networks embedded in living matter is an emerging
theme in synthetic biology. Synthetic networks have
allowed the creation of organisms endowed with
toggle switches, logic gates, pattern-forming
systems, oscillators, cellular sensors, new modes of
gene regulation and expanded genetic codes. A common
challenge of this work is the addition of specific
new functions to complex living organisms. This
requires spatial and temporal control of molecular
interactions and fluxes to achieve the desired
outcomes. Here we review recent successes in this
emerging field and discuss strategies for addressing
the challenges of increasing network complexity.},
PMID = 16710339,
ANNOTE = {synthetic biology review}
}
@ARTICLE{elowitz00,
AUTHOR = {Michael B. Elowitz and Stanislas Leibler},
TITLE = {A synthetic oscillatory network of transcriptional
regulators},
JOURNAL = {Nature},
YEAR = 2000,
VOLUME = 403,
NUMBER = 6767,
PAGES = {335--338},
MONTH = JAN,
ABSTRACT = {Networks of interacting biomolecules carry out many
essential functions in living cells, but the `design
principles' underlying the functioning of such
intracellular networks remain poorly understood,
despite intensive efforts including quantitative
analysis of relatively simple systems. Here we
present a complementary approach to this problem:
the design and construction of a synthetic network
to implement a particular function. We used three
transcriptional repressor systems that are not part
of any natural biological clock to build an
oscillating network, termed the repressilator, in
Escherichia coli. The network periodically induces
the synthesis of green fluorescent protein as a
readout of its state in individual cells. The
resulting oscillations, with typical periods of
hours, are slower than the cell-division cycle, so
the state of the oscillator has to be transmitted
from generation to generation. This artificial clock
displays noisy behaviour, possibly because of
stochastic fluctuations of its components. Such
`rational network design' may lead both to the
engineering of new cellular behaviours and to an
improved understanding of naturally occurring
networks.},
PMID = {10659856},
DOI = {doi:10.1038/35002125}
}
@ARTICLE{endy05,
AUTHOR = {Drew Endy},
TITLE = {Foundations for engineering biology},
JOURNAL = {Nature},
YEAR = 2005,
VOLUME = 438,
NUMBER = 7067,
PAGES = {449--453},
MONTH = NOV,
DOI = {doi:10.1038/nature04342},
ABSTRACT = {Engineered biological systems have been used to
manipulate information, construct materials, process
chemicals, produce energy, provide food, and help
maintain or enhance human health and our
environment. Unfortunately, our ability to quickly
and reliably engineer biological systems that behave
as expected remains quite limited. Foundational
technologies that make routine the engineering of
biology are needed. Vibrant, open research
communities and strategic leadership are necessary
to ensure that the development and application of
biological technologies remains overwhelmingly
constructive.},
PMID = 16306983
}
@MISC{endy05b,
KEY = {endy05},
AUTHOR = {Drew Endy},
TITLE = {Adventures in Synthetic Biology},
HOWPUBLISHED = {Nature},
MONTH = NOV,
ANNOTE = {comic strip},
YEAR = 2005,
URL = {http://www.nature.com/nature/comics/syntheticbiologycomic/index.html}
}
@ARTICLE{ferber04,
AUTHOR = {Dan Ferber},
TITLE = {Microbes Made to Order},
JOURNAL = {Science},
YEAR = 2004,
VOLUME = 303,
NUMBER = 5655,
PAGES = {158--161},
MONTH = JAN,
ABSTRACT = {A new breed of bioengineers aims to create microbes
from off-the-shelf parts. The parts are coming, but
will researchers be able to put them together?},
DOI = {doi:10.1126/science.303.5655.158}
}
@ARTICLE{gardner00,
AUTHOR = {Timothy S. Gardner and Charles R. Cantor and James
J. Collins},
TITLE = {Construction of a genetic toggle switch in {{\em
Escherichia coli}}},
JOURNAL = {Nature},
YEAR = 2000,
VOLUME = 403,
NUMBER = 6767,
PAGES = {339--342},
MONTH = JAN,
ABSTRACT = {It has been proposed that gene-regulatory circuits
with virtually any desired property can be
constructed from networks of simple regulatory
elements. These properties, which include
multistability and oscillations, have been found in
specialized gene circuits such as the bacteriophage
lambda switch and the Cyanobacteria circadian
oscillator. However, these behaviours have not been
demonstrated in networks of non-specialized
regulatory components. Here we present the
construction of a genetic toggle switch-a synthetic,
bistable gene-regulatory network-in Escherichia coli
and provide a simple theory that predicts the
conditions necessary for bistability. The toggle is
constructed from any two repressible promoters
arranged in a mutually inhibitory network. It is
flipped between stable states using transient
chemical or thermal induction and exhibits a nearly
ideal switching threshold. As a practical device,
the toggle switch forms a synthetic, addressable
cellular memory unit and has implications for
biotechnology, biocomputing and gene therapy.},
DOI = {doi:10.1038/35002131}
}
@ARTICLE{gibbs04,
AUTHOR = {W. Wayt Gibbs},
TITLE = {Synthetic Life},
JOURNAL = {Scientific American},
YEAR = 2004,
MONTH = MAY,
URL = {http://www.sciam.com/article.cfm?chanID=sa006&colID=1&articleID=0009FCA4-1A8F-1085-94F483414B7F0000},
ABSTRACT = {Biologists are crafting libraries of interchangeable
DNA parts and assembling them inside microbes to
create programmable, living machines.}
}
@ARTICLE{guet02,
AUTHOR = {C\u{a}lin C. Guet and Michael B. Elowitz and Weihong
Hsing and Stanislas Leibler},
TITLE = {Combinatorial Synthesis of Genetic Networks},
JOURNAL = {Science},
YEAR = 2002,
VOLUME = 296,
NUMBER = 5572,
PAGES = {1466--1470},
MONTH = MAY,
DOI = {doi:10.1126/science.1067407},
ABSTRACT = {A central problem in biology is determining how
genes interact as parts of functional
networks. Creation and analysis of synthetic
networks, composed of well-characterized genetic
elements, provide a framework for theoretical
modeling. Here, with the use of a combinatorial
method, a library of networks with varying
connectivity was generated in Escherichia
coli. These networks were composed of genes encoding
the transcriptional regulators LacI, TetR, and
lambda CI, as well as the corresponding
promoters. They displayed phenotypic behaviors
resembling binary logical circuits, with two
chemical ``inputs'' and a fluorescent protein
``output.'' Within this simple system, diverse
computational functions arose through changes in
network connectivity. Combinatorial synthesis
provides an alternative approach for studying
biological networks, as well as an efficient method
for producing diverse phenotypes in vivo.},
PMID = 12029133
}
@ARTICLE{hartwell99,
AUTHOR = {Leland H. Hartwell and John J. Hopfield and
Stanislas Leibler and Andrew W. Murray},
TITLE = {From molecular to modular cell biology},
JOURNAL = {Nature},
YEAR = 1999,
VOLUME = 402,
PAGES = {C47--C52},
MONTH = DEC,
DOI = {doi:10.1038/35011540},
ABSTRACT = { Cellular functions, such as signal transmission,
are carried out by `modules' made up of many species
of interacting molecules. Understanding how modules
work has depended on combining phenomenological
analysis with molecular studies. General principles
that govern the structure and behaviour of modules
may be discovered with help from synthetic sciences
such as engineering and computer science, from
stronger interactions between experiment and theory
in cell biology, and from an appreciation of
evolutionary constraints.},
PMID = 10591225
}
@ARTICLE{hasty02,
AUTHOR = {Jeff Hasty and David McMillen and J. J. Collins},
TITLE = {Engineered gene circuits},
JOURNAL = {Nature},
YEAR = 2002,
VOLUME = 420,
NUMBER = 6912,
PAGES = {224--230},
MONTH = NOV,
PMID = {12432407},
ABSTRACT = {A central focus of postgenomic research will be to
understand how cellular phenomena arise from the
connectivity of genes and proteins. This
connectivity generates molecular network diagrams
that resemble complex electrical circuits, and a
systematic understanding will require the
development of a mathematical framework for
describing the circuitry. From an engineering
perspective, the natural path towards such a
framework is the construction and analysis of the
underlying submodules that constitute the
network. Recent experimental advances in both
sequencing and genetic engineering have made this
approach feasible through the design and
implementation of synthetic gene networks amenable
to mathematical modelling and quantitative
analysis. These developments have signalled the
emergence of a gene circuit discipline, which
provides a framework for predicting and evaluating
the dynamics of cellular processes. Synthetic gene
networks will also lead to new logical forms of
cellular control, which could have important
applications in functional genomics, nanotechnology,
and gene and cell therapy.},
DOI = {doi:10.1038/nature01257}
}
@ARTICLE{isaacs04,
AUTHOR = {Farren J Isaacs and Daniel J Dwyer and Chunming Ding
and Dmitri D Pervouchine and Charles R Cantor and
James J Collins},
TITLE = {Engineered riboregulators enable
post-transcriptional control of gene expression},
JOURNAL = {Nature Biotechnology},
YEAR = 2004,
VOLUME = 22,
PAGES = {841--847},
MONTH = JUN,
DOI = {doi:10.1038/nbt986},
ABSTRACT = {Recent studies have demonstrated the important
enzymatic, structural and regulatory roles of RNA in
the cell. Here we present a post-transcriptional
regulation system in {\em Escherichia coli} that
uses RNA to both silence and activate gene
expression. We inserted a complementary {\em cis}
sequence directly upstream of the ribosome binding
site in a target gene. Upon transcription, this {\em
cis}-repressive sequence causes a stem-loop
structure to form at the 5'-untranslated region of
the mRNA. The stem-loop structure interferes with
ribosome binding, silencing gene expression. A small
noncoding RNA that is expressed in {\em trans}
targets the {\em cis}-repressed RNA with high
specificity, causing an alteration in the stem-loop
structure that activates expression. Such engineered
riboregulators may lend insight into mechanistic
actions of endogenous RNA-based processes and could
serve as scalable components of biological networks,
able to function with any promoter or gene to
directly control gene expression.}
}
@ARTICLE{kaern03,
AUTHOR = {Mads K\ae{}rn and William J. Blake and J.J. Collins},
TITLE = {The engineering of gene regulatory networks},
JOURNAL = {Annual Review of Biomedical Engineering},
YEAR = 2003,
VOLUME = 5,
PAGES = {179--206},
MONTH = AUG,
DOI = {doi:10.1146/annurev.bioeng.5.040202.121553},
ABSTRACT = {The rapid accumulation of genetic information and
advancement of experimental techniques have opened a
new frontier in biomedical engineering. With the
availability of well-characterized components from
natural gene networks, the stage has been set for
the engineering of artificial gene regulatory
networks with sophisticated computational and
functional capabilities. In these efforts, the
ability to construct, analyze, and interpret
qualitative and quantitative models is becoming
increasingly important. In this review, we consider
the current state of gene network engineering from a
combined experimental and modeling perspective. We
discuss how networks with increased complexity are
being constructed from simple modular components and
how quantitative deterministic and stochastic
modeling of these modules may provide the foundation
for accurate in silico representations of gene
regulatory network function in vivo. },
PMID = 14527313
}
@ARTICLE{kobayashi04,
AUTHOR = {Hideki Kobayashi and Mads K\ae{}rn and Michihiro
Araki and Kristy Chung and Timothy S. Gardner and
Charles R. Cantor and James J. Collins},
TITLE = {Programmable cells: Interfacing natural and
engineered gene networks},
JOURNAL = {Proc. Natl. Acad. Sci. USA},
YEAR = 2004,
VOLUME = 101,
NUMBER = 22,
PAGES = {8414--8419},
MONTH = JUN,
DOI = {doi:10.1073/pnas.0402940101},
ABSTRACT = {Novel cellular behaviors and characteristics can be
obtained by coupling engineered gene networks to the
cell's natural regulatory circuitry through
appropriately designed input and output
interfaces. Here, we demonstrate how an engineered
genetic circuit can be used to construct cells that
respond to biological signals in a predetermined and
programmable fashion. We employ a modular design
strategy to create {\em Escherichia coli} strains
where a genetic toggle switch is interfaced with:
(i) the SOS signaling pathway responding to DNA
damage, and (ii) a transgenic quorum sensing
signaling pathway from {\em Vibrio fischeri}. The
genetic toggle switch endows these strains with
binary response dynamics and an epigenetic
inheritance that supports a persistent phenotypic
alteration in response to transient signals. These
features are exploited to engineer cells that form
biofilms in response to DNA-damaging agents and
cells that activate protein synthesis when the cell
population reaches a critical density. Our work
represents a step toward the development of
``plug-and-play'' genetic circuitry that can be used
to create cells with programmable behaviors.},
PMID = 15159530
}
@ARTICLE{kramer04,
AUTHOR = {Beat P Kramer and Alessandro Usseglio Viretta and
Marie Daoud-El Baba and Dominique Aubel and Wilfried
Weber and Martin Fussenegger},
TITLE = {An engineered epigenetic transgene switch in
mammalian cells},
JOURNAL = {Nature Biotechnology},
YEAR = 2004,
VOLUME = 22,
PAGES = {867--870},
MONTH = JUN,
DOI = {doi:10.1038/nbt980},
ABSTRACT = {In multicellular systems cell identity is imprinted
by epigenetic regulation circuits, which determine
the global transcriptome of adult cells in a cell
phenotype-specific manner. By combining two
repressors, which control each other's expression,
we have developed a mammalian epigenetic circuitry
able to switch between two stable transgene
expression states after transient administration of
two alternate drugs. Engineered Chinese hamster
ovary cells (CHO-K1) showed toggle switch-specific
expression profiles of a human glycoprotein in
culture, as well as after microencapsulation and
implantation into mice. Switch dynamics and
expression stability could be predicted with
mathematical models. Epigenetic transgene control
through toggle switches is an important tool for
engineering artificial gene networks in mammalian
cells.}
}
@ARTICLE{levskaya05,
AUTHOR = {Anselm Levskaya and Aaron A. Chevalier and Jeffrey
J. Tabor and Zachary Booth Simpson and Laura
A. Lavery and Matthew Levy and Eric A. Davidson and
Alexander Scouras and Andrew D. Ellington and Edward
M. Marcotte and Christopher A. Voigt},
TITLE = {Synthetic biology: Engineering {{\em Escherichia
coli}} to see light},
JOURNAL = {Nature},
YEAR = 2005,
VOLUME = 438,
NUMBER = 7067,
PAGES = {441--442},
MONTH = NOV,
DOI = {doi:10.1038/nature04405},
ABSTRACT = {We have designed a bacterial system that is switched
between different states by red light. The system
consists of a synthetic sensor kinase that allows a
lawn of bacteria to function as a biological film,
such that the projection of a pattern of light on to
the bacteria produces a high-definition (about 100
megapixels per square inch), two-dimensional
chemical image. This spatial control of bacterial
gene expression could be used to 'print' complex
biological materials, for example, and to
investigate signalling pathways through precise
spatial and temporal control of their
phosphorylation steps.},
PMID = 16306980
}
@ARTICLE{mcdaniel05,
AUTHOR = {Ryan McDaniel and Ron Weiss},
TITLE = {Advances in synthetic biology: on the path from
prototypes to applications},
JOURNAL = {Current Opinion in Biotechnology},
YEAR = 2005,
VOLUME = 16,
NUMBER = 4,
PAGES = {476--483},
MONTH = AUG,
DOI = {doi:10.1016/j.copbio.2005.07.002},
PMID = 16019200
}
@ARTICLE{mehl03,
AUTHOR = {Ryan A. Mehl and J. Christopher Anderson and Stephen
W. Santoro and Lei Wang and Andrew B. Martin and
David S. King and David M. Horn and Peter
G. Schultz},
TITLE = {Generation of a Bacterium with a 21 Amino Acid
Genetic Code},
JOURNAL = {JACS},
YEAR = 2003,
VOLUME = 125,
NUMBER = 4,
PAGES = {935--939},
DOI = {doi:10.1021/ja0284153},
ABSTRACT = {We have generated a completely autonomous bacterium
with a 21 amino acid genetic code. This bacterium
can biosynthesize a nonstandard amino acid from
basic carbon sources and incorporate this amino acid
into proteins in response to the amber nonsense
codon. The biosynthetic pathway for the amino acid
p-aminophenylalanine (pAF) as well as a unique pAF
synthetase and cognate tRNA were added to
Escherichia coli. Denaturing gel electrophoresis and
mass spectrometric analysis show that pAF is
incorporated into myoglobin with fidelity and
efficiency rivaling those of the common 20 amino
acids. This and other such organisms may provide an
opportunity to examine the evolutionary consequences
of adding new amino acids to the genetic repertoire,
as well as generate proteins with new or enhanced
biological functions.},
PMID = 12537491
}
@ARTICLE{morton05,
AUTHOR = {Oliver Morton},
TITLE = {Life, Reinvented},
JOURNAL = {Wired},
YEAR = 2005,
VOLUME = 13,
NUMBER = 1,
MONTH = JAN,
ABSTRACT = {A group of MIT engineers wanted to model the
biological world. But, damn, some of nature's
designs were complicated! So they started rebuilding
from the ground up - and gave birth to synthetic
biology.},
URL = {http://www.wired.com/wired/archive/13.01/mit.html}
}
@ARTICLE{rackham05,
AUTHOR = {Oliver Rackham and Jason W Chin},
TITLE = {A network of orthogonal ribosome $\cdot$ {mRNA} pairs},
JOURNAL = {Nature Chemical Biology},
YEAR = 2005,
VOLUME = 1,
NUMBER = 3,
PAGES = {159--166},
MONTH = AUG,
DOI = {doi:10.1038/nchembio719},
ABSTRACT = {Synthetic biology promises the ability to program
cells with new functions. Simple oscillators,
switches, logic functions, cell-cell communication
and pattern-forming circuits have been created by
the connection of a small set of natural
transcription factors and their binding sites in
different ways to produce different networks of
molecular interactions. However, the controlled
synthesis of more complex synthetic networks and
functions will require an expanded set of functional
molecules with known molecular specificities. Here,
we tailored the molecular specificity of duplicated
Escherichia coli ribosome mRNA pairs with respect to
the wild-type ribosome and mRNAs to produce multiple
orthogonal ribosome orthogonal mRNA pairs that can
process information in parallel with, but
independent of, their wild-type progenitors. In
these pairs, the ribosome exclusively translates the
orthogonal mRNA, and the orthogonal mRNA is not a
substrate for cellular ribosomes. We predicted and
measured the network of interactions between
orthogonal ribosomes and orthogonal mRNAs, and
showed that they can be used to
post-transcriptionally program the cell with Boolean
logic.}
}
@ARTICLE{rackham05b,
AUTHOR = {Oliver Rackham and Jason W. Chin},
TITLE = {Cellular Logic with Orthogonal Ribosomes},
JOURNAL = {Journal of the American Chemical Society},
YEAR = 2005,
VOLUME = 127,
NUMBER = 50,
PAGES = {17584--17585},
DOI = {doi:10.1021/ja055338d},
ABSTRACT = {The creation and use of unnatural molecules to
control cellular function is a long standing goal of
the chemical community, but in general, these
efforts have been directed at finding molecules to
inhibit or activate a particular molecular target or
function, or to elicit a particular phenotype. Here
we show that multiple unnatural molecules
(orthogonal ribosomes) can be used combinatorially,
in a single cell, to program Boolean logic
functions. These experiments show how attention to
the molecular specificity of noncovalent
interactions between unnatural macromolecules allows
the synthesis of complex function from the
"bottom-up" in living matter.}
}
@ARTICLE{shimizu-sato02,
AUTHOR = {Sae Shimizu-Sato and Enamul Huq and James
M. Tepperman and Peter H. Quail},
TITLE = {A light-switchable gene promoter system},
JOURNAL = {Nature Biotechnology},
YEAR = 2002,
VOLUME = 20,
NUMBER = 10,
PAGES = {1041--1044},
MONTH = OCT
}
@ARTICLE{simpson04,
AUTHOR = {Michael L. Simpson and Chris D. Cox and Gregory
D. Peterson and Gary S. Sayler},
TITLE = {Engineering in the Biological Substrate: Information
Processing in Genetic Circuits},
JOURNAL = {Proceedings of the {IEEE}},
YEAR = 2004,
VOLUME = 92,
NUMBER = 5,
PAGES = {848--863},
MONTH = MAY,
ABSTRACT = {We review the rapidly evolving efforts to analyze,
model, simulate, and engineer genetic and
biochemical information processing systems within
living cells. We begin by showing that the
fundamental elements of information processing in
electronic and genetic systems are strikingly
similar, and follow this theme through a review of
efforts to create synthetic genetic circuits. In
particular, we describe and review the ``silicon
mimetic'' approach, where genetic circuits are
engineered to mimic the functionality of
semiconductor devices such as logic gates, latched
circuits, and oscillators. This is followed with a
review of the analysis, modeling, and simulation of
natural and synthetic genetic circuits, which often
proceed in a manner similar to that used for
electronic systems. We conclude by presenting
examples of naturally occurring genetic and
biochemical systems that recently have been
conceptualized in terms familiar to systems
engineers. Our review of these newly forming fields
of research demonstrates that the expertise and
skills contained within electrical and computer
engineering disciplines apply not only to design
within biological systems, but also to the
development of a deeper understanding of biological
functionality. This review of these efforts points
to the emergence of both engineering and basic
science disciplines following parallel paths.},
DOI = {doi:10.1109/JPROC.2004.826600}
}
@ARTICLE{sprinzak05,
AUTHOR = {David Sprinzak and Michael B. Elowitz},
TITLE = {Reconstruction of genetic circuits},
JOURNAL = {Nature},
YEAR = 2005,
VOLUME = 438,
NUMBER = 7067,
PAGES = {443--448},
MONTH = NOV,
DOI = {doi:10.1038/nature04335},
ABSTRACT = {The complex genetic circuits found in cells are
ordinarily studied by analysis of genetic and
biochemical perturbations. The inherent modularity
of biological components like genes and proteins
enables a complementary approach: one can construct
and analyse synthetic genetic circuits based on
their natural counterparts. Such synthetic circuits
can be used as simple in vivo models to explore the
relation between the structure and function of a
genetic circuit. Here we describe recent progress in
this area of synthetic biology, highlighting newly
developed genetic components and biological lessons
learned from this approach.},
PMID = 16306982
}
@ARTICLE{stojanovic03,
AUTHOR = {Milan N. Stojanovic and Darko Stefanovic},
TITLE = {A deoxyribozyme-based molecular automaton},
JOURNAL = {Nature Biotechnology},
YEAR = 2003,
VOLUME = 21,
NUMBER = 9,
PAGES = {1069--1074},
MONTH = SEP,
PMID = 12923549,
DOI = {doi:10.1038/nbt862},
ABSTRACT = {We describe a molecular automaton, called MAYA,
which encodes a version of the game of tic-tac-toe
and interactively competes against a human
opponent. The automaton is a Boolean network of
deoxyribozymes that incorporates 23 molecular-scale
logic gates and one constitutively active
deoxyribozyme arrayed in nine wells (3x3)
corresponding to the game board. To make a move,
MAYA carries out an analysis of the input
oligonucleotide keyed to a particular move by the
human opponent and indicates a move by fluorescence
signaling in a response well. The cycle of human
player input and automaton response continues until
there is a draw or a victory for the automaton. The
automaton cannot be defeated because it implements a
perfect strategy.}
}
@ARTICLE{yokobayashi02,
AUTHOR = {Yohei Yokobayashi and Ron Weiss and Frances
H. Arnold},
TITLE = {Directed evolution of a genetic circuit},
JOURNAL = {Proc. Natl. Acad. Sci. USA},
YEAR = 2002,
VOLUME = 99,
NUMBER = 26,
PAGES = {16587--16591},
MONTH = DEC,
PMID = {12451174},
ABSTRACT = {The construction of artificial networks of
transcriptional control elements in living cells
represents a new frontier for biological
engineering. However, biological circuit engineers
will have to confront their inability to predict the
precise behavior of even the most simple synthetic
networks, a serious shortcoming and challenge for
the design and construction of more sophisticated
genetic circuitry in the future. We propose a
combined rational and evolutionary design strategy
for constructing genetic regulatory circuits, an
approach that allows the engineer to fine-tune the
biochemical parameters of the networks
experimentally {\em in vivo}. By applying directed
evolution to genes comprising a simple genetic
circuit, we demonstrate that a nonfunctional circuit
containing improperly matched components can evolve
rapidly into a functional one. In the process, we
generated a library of genetic devices with a range
of behaviors that can be used to construct more
complex circuits.},
DOI = {doi:10.1073/pnas.252535999}
}
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