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 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 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kobayashi H,Kaern M,Araki M,Chung K,Gardner TS,Cantor CR,Collins JJdoi
10.1073/pnas.0402940101keywords:
subject
Has Abstractpub_date
2004-06-01 00:00:00pages
8414-9issue
22eissn
0027-8424issn
1091-6490pii
0402940101journal_volume
101pub_type
杂志文章abstract::The only known product of the Snyder-Theilen strain of feline sarcoma virus (ST-FeSV) is a 85,000-dalton protein, designated ST P85, that contains feline leukemia virus gag gene encoded proteins (p15, p12, and a fragment of p30) and a sarcoma virus-specific polypeptide. Antibodies directed against the latter immunopre...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.9.5158
更新日期:1980-09-01 00:00:00
abstract::Construction of deletion derivative plasmids and cloning of restriction fragments from plasmids containing the Salmonella typhimurium origin of replication (ori) were used to locate the functional origin to within a DNA fragment of 296 base pairs between the genes uncB and asn. The nucleotide sequence of the S. typhim...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.5.2460
更新日期:1980-05-01 00:00:00
abstract::A gene-transfer approach was used to explore the function of the BCL2 (B-cell lymphoma/leukemia 2) gene in a human T-cell line, Jurkat. Though stable introduction of a BCL2 expression plasmid into Jurkat T cells was by itself insufficient, the combined transfer of BCL2 and MYC genes markedly enhanced the tumorigenicit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.10.3660
更新日期:1990-05-01 00:00:00
abstract::5-enol-Pyruvylshikimate-3-phosphate synthase (EPSP synthase; phosphoenolpyruvate:3-phosphoshikimate 1-carboxyvinyltransferase, EC 2.5.1.19) is an enzyme on the pathway toward the synthesis of aromatic amino acids in plants, fungi, and bacteria and is the target of the broad-spectrum herbicide glyphosate. The three-dim...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.11.5046
更新日期:1991-06-01 00:00:00
abstract::A segment of DNA containing cya, the gene for adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1], has been isolated from Salmonella typhimurium. The phage lambda gt4 was used as a cloning vector and adenylate cyclase-positive hybrid phages were isolated that complemented adenylate cyclase-negative bac...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.8.4684
更新日期:1981-08-01 00:00:00
abstract::Activated thiol-Sepharose [agarose-(glutathione-2-pyridyl disulfide) conjugate] has been used to immobilize proteins with a single or a few thiol groups via disulfide bridges. The immobilized proteins were subsequently proteolytically degraded. After washing, the thiol-containing peptides were eluted with a reducing a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.72.8.3029
更新日期:1975-08-01 00:00:00
abstract::This paper explores the explanations for, and consequences of, the early appearance of food production outside the Fertile Crescent of Southwest Asia, where it originated in the 10th/9th millennia cal BC. We present evidence that cultivation appeared in Central Anatolia through adoption by indigenous foragers in the m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1800163115
更新日期:2018-04-03 00:00:00
abstract::Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and the glutathione-dependent form...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.19.9247
更新日期:1992-10-01 00:00:00
abstract::A polar lipid containing about 20 per cent of the lipid soluble inositol has been purified from cells of Saccharomyces cerevisiae. This compound labeled with (3)H-inositol, (32)P(i), or (14)C glucose was isolated from aqueous pyridine extracts by means of paper chromatography. Unlabeled compound was obtained by a diff...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.64.3.1042
更新日期:1969-11-01 00:00:00
abstract::Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca(2+) inf...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1500525112
更新日期:2015-09-22 00:00:00
abstract::The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.16.7686
更新日期:1993-08-15 00:00:00
abstract::Differentiation-inducing factor 1 [DIF-1; 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)-hexan-1-one] induces stalk cell differentiation during Dictyostelium development. It is present as a gradient in the multicellular slug, its lowest concentration being in the anterior. Here we demonstrate the existence of a locali...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.2.487
更新日期:1993-01-15 00:00:00
abstract::A spectroscopic interpretation of incoherent neutron scattering experiments is presented which is based on Franck-Condon-type probabilities for scattering-induced transitions between quantum states of the target. The resulting expressions for the scattering functions enable an energy landscape-oriented analysis of neu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1718720115
更新日期:2018-09-18 00:00:00
abstract::Nations in the 21st century face a complex mix of environmental and social challenges, as highlighted by the on-going Sustainable Development Goals process. The "planetary boundaries" concept [Rockström J, et al. (2009) Nature 461(7263):472-475], and its extension through the addition of social well-being indicators t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1400985111
更新日期:2014-10-21 00:00:00
abstract::All available complete mitochondrial genomes (21 species) are evaluated for dinucleotide over- and under-representation. The CpG dinucleotide is pervasively under-represented in all animal mitochondria, but it is of variable relative abundance in fungal, protist, and plant mitochondrial genomes. Interpretations and hy...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.9.3799
更新日期:1994-04-26 00:00:00
abstract::We define an integer invariant [Formula: see text] of a smooth, compact, closed 4-manifold X by minimizing a certain complexity of a trisection of X over all trisections. The good feature of [Formula: see text] is that when [Formula: see text] and X is a homology 4-sphere, then X is diffeomorphic to the 4-sphere. Natu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1718953115
更新日期:2018-10-23 00:00:00
abstract::We use stable isotope ratios in feces of wild mountain gorillas (Gorilla beringei) to test the hypothesis that diet shifts within a single year, as measured by dry mass intake, can be recovered. Isotopic separation of staple foods indicates that intraannual changes in the isotopic composition of feces reflect shifts i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1215782109
更新日期:2012-12-26 00:00:00
abstract::Complex phenotypes can be modeled as networks of component traits connected by genetic, developmental, or functional interactions. Aposematism, which has evolved multiple times in poison frogs (Dendrobatidae), links a warning signal to a chemical defense against predators. Other traits are involved in this complex phe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1010952108
更新日期:2011-04-12 00:00:00
abstract::Efforts to understand the dramatic declines in mortality over the past century have focused on life expectancy. However, understanding changes in disparity in age of death is important to understanding mechanisms of mortality improvement and devising policy to promote health equity. We derive a novel decomposition of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1601112113
更新日期:2016-07-26 00:00:00
abstract::Populations of jellyfish, Mastigias sp., landlocked in tropical marine lakes during the Holocene, show extreme genetic isolation (0.74 < or = phiST < or = 1.00), founder effects (genetic diversity: 0.000 < or = pi < or = 0.001), rapid morphological evolution, and behavioral adaptation. These results demonstrate incipi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0503635102
更新日期:2005-06-28 00:00:00
abstract::To scrutinize how a protein folds at atomic resolution, we performed 200 molecular dynamics simulations (each of 50 ns) of the miniprotein Trp-cage on the computational grid. Within the trajectories, 58 folding and 31 unfolding events were identified and subjected to extensive comparison and classification. Based on a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0407015102
更新日期:2004-12-21 00:00:00
abstract::Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus of the family Paramyxoviridae and are unique in that they exhibit a broad species tropism and cause fatal disease in both animals and humans. They infect cells through a pH-independent membrane fusion process mediated by their fusion and attachme...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0504887102
更新日期:2005-07-26 00:00:00
abstract::Transcription initiation factor TFIID is a multimeric protein complex that plays a central role in transcriptional regulation by facilitating promoter responses to various activators. cDNAs encoding the 110-kDa subunit of Drosophila TFIID (p110) were isolated with a degenerate oligodeoxynucleotide probe based on an am...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.13.5896
更新日期:1993-07-01 00:00:00
abstract::ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidate...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1320350111
更新日期:2014-04-22 00:00:00
abstract::The Zika virus (ZIKV) causes microcephaly and the Guillain-Barré syndrome. Little is known about how ZIKV causes these conditions or which ZIKV viral protein(s) is responsible for the associated ZIKV-induced cytopathic effects, including cell hypertrophy, growth restriction, cell-cycle dysregulation, and cell death. W...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1619735114
更新日期:2017-01-17 00:00:00
abstract::We have developed a cell-free system to study bacteriophage lambda DNA replication. Maximal DNA synthesis in vitro requires the four deoxynucleoside triphosphates, ATP, and exogenous lambda DNA. DNA synthesis requires the products of the phage O and P genes but is not inhibited by lambda repressor. The kinetics of syn...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.5.1758
更新日期:1974-05-01 00:00:00
abstract::In a significant fraction of the Escherichia coli cytosolic proteins, the N-terminal methionine residue incorporated during the translation initiation step is excised. The N-terminal methionine excision is catalyzed by methionyl-aminopeptidase (MAP). Previous studies have suggested that the action of this enzyme could...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.21.8247
更新日期:1989-11-01 00:00:00
abstract::Molecular beacons are FRET-based target-activatable probes. They offer control of fluorescence emission in response to specific cancer targets, thus are useful tools for in vivo cancer imaging. Photodynamic therapy (PDT) is a cell-killing process by light activation of a photosensitizer (PS) in the presence of oxygen....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0611142104
更新日期:2007-05-22 00:00:00
abstract::Erythroid Krüppel-like factor (EKLF), which binds to the CACCC box in the beta-globin promoter, is required for the expression of the beta-globin gene in adult erythroid cells. It was recently demonstrated that EKLF is also required for the activity of the beta-globin locus control region (LCR) 5'HS3. Some evidence su...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.18.10051
更新日期:1999-08-31 00:00:00
abstract::A photosensitizer conjugate, chlorin e6 (Ce6) covalently bound to 1-micron-diameter polystyrene microspheres, has been investigated in the photodynamic destruction of MGH-U1 human bladder carcinoma cells in vitro. The microspheres were taken up avidly by the carcinoma cells; confocal laser scanning fluorescence micros...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.4.1580
更新日期:1991-02-15 00:00:00