Provider: Quertle (www.quertle.info)
Content: text/plain; charset=UTF-8

TY - JOUR
TI - How molecular should your molecular model be? On the level of molecular detail required to simulate biological networks in systems and synthetic biology.
AU - Gonze, Didier
AU - Abou-Jaoudé, Wassim
AU - Ouattara, Djomangan Adama
AU - Halloy, José
PY - 2011
T2 - Methods in enzymology
J2 - Methods Enzymol
UR - http://www.ncbi.nlm.nih.gov/pubmed/21187226
VL - 487
SP - 171-215
N2 - The recent advance of genetic studies and the rapid accumulation of molecular data, together with the increasing performance of computers, led researchers to design more and more detailed mathematical models of biological systems. Many modeling approaches rely on ordinary differential equations (ODE) which are based on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed commonly used in dynamical models in systems and synthetic biology because they provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit-cycle oscillations or multistability). For most of the systems modeled, the actual molecular mechanism is unknown, and the enzyme equations should be regarded as phenomenological. In this chapter, we discuss the validity and accuracy of these approximations. In particular, we focus on the validity of the Michaelis-Menten function for open systems and on the use of Hill kinetics to describe transcription rates of regulated genes. Our discussion is illustrated by numerical simulations of prototype systems, including the Repressilator (a genetic oscillator) and the Toggle Switch model (a bistable system). We systematically compare the results obtained with the compact version (based on Michaelis-Menten and Hill functions) with its corresponding developed versions (based on "elementary" reaction steps and mass action laws). We also discuss the use of compact approaches to perform stochastic simulations (Gillespie algorithm). On the basis of these results, we argue that using compact models is suitable to model qualitatively biological systems.
N1 - Exported from www.Quertle.info. Search query: Synthetic biology.
ER -

TY - JOUR
TI - Large-Scale Discovery and Characterization of Protein Regulatory Motifs in Eukaryotes
AU - Lieber, Daniel S
AU - Elemento, Olivier
AU - Tavazoie, Saeed
PY - 2010
T2 - PLoS ONE
J2 - PLoS One
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012054/
VL - 5
IS - 12
DO - 10.1371/journal.pone.0014444
C2 - 3012054
N2 - The increasing ability to generate large-scale, quantitative proteomic data has brought with it the challenge of analyzing such data to discover the sequence elements that underlie systems-level protein behavior. Here we show that short, linear protein motifs can be efficiently recovered from proteome-scale datasets such as sub-cellular localization, molecular function, half-life, and protein abundance data using an information theoretic approach. Using this approach, we have identified many known protein motifs, such as phosphorylation sites and localization signals, and discovered a large number of candidate elements. We estimate that ∼80% of these are novel predictions in that they do not match a known motif in both sequence and biological context, suggesting that post-translational regulation of protein behavior is still largely unexplored. These predicted motifs, many of which display preferential association with specific biological pathways and non-random positioning in the linear protein sequence, provide focused hypotheses for experimental validation.
N1 - Exported from www.Quertle.info. Search query: Synthetic biology.
ER -

TY - JOUR
TI - Exploiting plug-and-play synthetic biology for drug discovery and production in microorganisms.
AU - Medema, Marnix H
AU - Breitling, Rainer
AU - Bovenberg, Roel
AU - Takano, Eriko
PY - 2010
T2 - Nature reviews. Microbiology
J2 - Nat Rev Microbiol
UR - http://www.ncbi.nlm.nih.gov/pubmed/21189477
N2 - One of the most promising applications of synthetic biology is the biosynthesis of new drugs from secondary metabolites. Here, we survey a wide range of strategies that control the activity of biosynthetic modules in the cell in space and time, and illustrate how these strategies can be used to design efficient cellular synthetic production systems. Re-engineered versions of secondary metabolite biosynthetic pathways identified from any genomic sequence can then be inserted into these systems in a plug-and-play fashion.
N1 - Exported from www.Quertle.info. Search query: Synthetic biology.
ER -

TY - JOUR
TI - Introduction of customized inserts for streamlined assembly and optimization of BioBrick synthetic genetic circuits.
AU - Norville, Julie E
AU - Derda, Ratmir
AU - Gupta, Saurabh
AU - Drinkwater, Kelly A
AU - Belcher, Angela M
AU - Leschziner, Andres E
AU - Knight, Thomas F, Jr
PY - 2010
T2 - Journal of biological engineering
J2 - J Biol Eng
UR - http://www.ncbi.nlm.nih.gov/pubmed/21172029
VL - 4
IS - 1
SP - 17
N2 - ABSTRACT: BACKGROUND: BioBrick standard biological parts are designed to make biological systems easier to engineer (e.g. assemble, manipulate and modify). There are over 5,000 parts available in the Registry of Standard Biological Parts that can be easily assembled into genetic circuits using a standard assembly technique. The standardization of the assembly technique has allowed for wide distribution to a large number of users -- the parts are reusable and interchangeable during the assembly process. The standard assembly process, however, has some limitations. In particular it does not allow for modification of already assembled biological circuits, addition of protein tags to pre-existing BioBrick parts, or addition of non-BioBrick parts to assemblies. RESULTS: In this paper we describe a simple technique for rapid generation of synthetic biological circuits using introduction of customized inserts. We demonstrate its use in Escherichia coli (E. coli) to express green fluorescent protein (GFP) at pre-calculated relative levels and to add an N-terminal tag to GFP. The technique uses a new BioBrick part (called a BioScaffold) that can be inserted into cloning vectors and excised from them to leave a gap into which other DNA elements can be placed. The removal of the BioScaffold is performed by a Type IIB restriction enzyme (REase) that recognizes the BioScaffold but cuts into the surrounding sequences; therefore, the placement and removal of the BioScaffold allows the creation of seamless connections between arbitrary DNA sequences in cloning vectors. The BioScaffold contains a built-in red fluorescent protein (RFP) reporter; successful insertion of the BioScaffold is, thus, accompanied by gain of red fluorescence and its removal is manifested by disappearance of the red fluorescence. CONCLUSIONS: The ability to perform targeted modifications of existing BioBrick circuits with BioScaffolds (1) simplifies and speeds up the iterative design-build-test process through direct reuse of existing circuits, (2) allows incorporation of sequences incompatible with BioBrick assembly into BioBrick circuits (3) removes scar sequences between standard biological parts, and (4) provides a route to adapt synthetic biology innovations to BioBrick assembly through the creation of new parts rather than new assembly standards or parts collections.
N1 - Exported from www.Quertle.info. Search query: Synthetic biology.
ER -

TY - JOUR
TI - Cellulase-Xylanase Synergy in Designer Cellulosomes for Enhanced Degradation of a Complex Cellulosic Substrate
AU - Moraïs, Sarah
AU - Barak, Yoav
AU - Caspi, Jonathan
AU - Hadar, Yitzhak
AU - Lamed, Raphael
AU - Shoham, Yuval
AU - Wilson, David B
AU - Bayer, Edward A
PY - 2010
T2 - mBio
J2 - mBio
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999897/
VL - 1
IS - 5
DO - 10.1128/mBio.00285-10
C2 - 2999897
N2 - IMPORTANCE: Global efforts towards alternative energy programs are highlighted by processes for converting plant-derived carbohydrates to biofuels. The major barrier in such processes is the inherent recalcitrance to enzymatic degradation of cellulose combined with related associated polysaccharides. The multienzyme cellulosome complexes, produced by anaerobic bacteria, are considered to be the most efficient systems for degradation of plant cell wall biomass. In the present work, we have employed a synthetic biology approach by producing artificial designer cellulosomes of predefined enzyme composition and architecture. The engineered tetravalent cellulosome complexes contain two different types of cellulases and two distinct xylanases. Using this approach, enhanced synergistic activity was observed on wheat straw, a natural recalcitrant substrate. The present work strives to gain insight into the combined action of cellulosomal enzyme components towards the development of advanced systems for improved degradation of cellulosic material.
N1 - Exported from www.Quertle.info. Search query: Synthetic biology.
ER -