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Schwille P 《Science (New York, N.Y.)》2011,333(6047):1252-1254
How synthetic can "synthetic biology" be? A literal interpretation of the name of this new life science discipline invokes expectations of the systematic construction of biological systems with cells being built module by module--from the bottom up. But can this possibly be achieved, taking into account the enormous complexity and redundancy of living systems, which distinguish them quite remarkably from design features that characterize human inventions? There are several recent developments in biology, in tight conjunction with quantitative disciplines, that may bring this literal perspective into the realm of the possible. However, such bottom-up engineering requires tools that were originally designed by nature's greatest tinkerer: evolution. 相似文献
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Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits. 相似文献
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The models and simulation tools available to design functionally complex synthetic biological devices are very limited. We formulated a design-driven approach that used mechanistic modeling and kinetic RNA folding simulations to engineer RNA-regulated genetic devices that control gene expression. Ribozyme and metabolite-controlled, aptazyme-regulated expression devices with quantitatively predictable functions were assembled from components characterized in vitro, in vivo, and in silico. The models and design strategy were verified by constructing 28 Escherichia coli expression devices that gave excellent quantitative agreement between the predicted and measured gene expression levels (r = 0.94). These technologies were applied to engineer RNA-regulated controls in metabolic pathways. More broadly, we provide a framework for studying RNA functions and illustrate the potential for the use of biochemical and biophysical modeling to develop biological design methods. 相似文献
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Advancing approach and toolbox in optimization of chloroplast genetic transformation technology 
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下载免费PDF全文 《农业科学学报》2023,22(7):1951-1966
Chloroplast is a discrete, highly structured, and semi-autonomous cellular organelle. The small genome of chloroplast makes it an up-and-coming platform for synthetic biology. As a special means of synthetic biology, chloroplast genetic engineering shows excellent potential in reconstructing various sophisticated metabolic pathways within the plants for specific purposes, such as improving crop photosynthetic capacity, enhancing plant stress resistance, and synthesizing new drugs and vaccines. However, many plant species exhibit limited efficiency or inability in chloroplast genetic transformation. Hence, new transformation technologies and tools are being constantly developed. In order to further expand and facilitate the application of chloroplast genetic engineering, this review summarizes the new technologies in chloroplast genetic transformation in recent years and discusses the choice of appropriate synthetic biological elements for the construction of efficient chloroplast transformation vectors. 相似文献
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Synthetic biology is an emerging field focused on engineering biomolecular systems and cellular capabilities for a variety of applications. Substantial progress began a little over a decade ago with the creation of synthetic gene networks inspired by electrical engineering. Since then, the field has designed and built increasingly complex circuits and constructs and begun to use these systems in a variety of settings, including the clinic. These efforts include the development of synthetic biology therapies for the treatment of infectious diseases and cancer, as well as approaches in vaccine development, microbiome engineering, cell therapy, and regenerative medicine. Here, we highlight advances in the biomedical application of synthetic biology and discuss the field's clinical potential. 相似文献
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[目的]新型自动气象站设备的稳定运行和保障十分重要,针对业务运行中外围设备面临的实际问题,本研究分别从数据本地传输线路和保障电源两方面,提出合理可行的改进设计思路和解决方案。[方法]主要方法是数据本地传输线路新增备用线路,解决线路单一和软件功能限制问题;电源方面改进UPS布局和发电机电路,使保障电源更完善。[结果]结果表明,新设计的数据传输线路实现多重备份,改进后保障电源有2套UPS主机和电池组互为备份,发电机操作实现无人值守。改造简单成本合理,操作安全布局清晰,实现新型自动气象站外围设备的全面保障。[结论]本研究以成熟稳定的设计、合理的成本,为新型自动气象站外围设备保障设计提供最优方案,确保新型站设备的稳定运行和全面保障,为气象现代化建设提供科学依据。 相似文献
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Cell surface engineering by a modified Staudinger reaction 总被引：1，自引：0，他引：1
Selective chemical reactions enacted within a cellular environment can be powerful tools for elucidating biological processes or engineering novel interactions. A chemical transformation that permits the selective formation of covalent adducts among richly functionalized biopolymers within a cellular context is presented. A ligation modeled after the Staudinger reaction forms an amide bond by coupling of an azide and a specifically engineered triarylphosphine. Both reactive partners are abiotic and chemically orthogonal to native cellular components. Azides installed within cell surface glycoconjugates by metabolism of a synthetic azidosugar were reacted with a biotinylated triarylphosphine to produce stable cell-surface adducts. The tremendous selectivity of the transformation should permit its execution within a cell's interior, offering new possibilities for probing intracellular interactions. 相似文献
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Kochendoerfer GG Chen SY Mao F Cressman S Traviglia S Shao H Hunter CL Low DW Cagle EN Carnevali M Gueriguian V Keogh PJ Porter H Stratton SM Wiedeke MC Wilken J Tang J Levy JJ Miranda LP Crnogorac MM Kalbag S Botti P Schindler-Horvat J Savatski L Adamson JW Kung A Kent SB Bradburne JA 《Science (New York, N.Y.)》2003,299(5608):884-887
We report the design and total chemical synthesis of "synthetic erythropoiesis protein" (SEP), a 51-kilodalton protein-polymer construct consisting of a 166-amino-acid polypeptide chain and two covalently attached, branched, and monodisperse polymer moieties that are negatively charged. The ability to control the chemistry allowed us to synthesize a macromolecule of precisely defined covalent structure. SEP was homogeneous as shown by high-resolution analytical techniques, with a mass of 50,825 +/-10 daltons by electrospray mass spectrometry, and with a pI of 5.0. In cell and animal assays for erythropoiesis, SEP displayed potent biological activity and had significantly prolonged duration of action in vivo. These chemical methods are a powerful tool in the rational design of protein constructs with potential therapeutic applications. 相似文献
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Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics. 相似文献
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Scaffold proteins link signaling molecules into linear pathways by physically assembling them into complexes. Scaffolds may also have a higher-order role as signal-processing hubs, serving as the target of feedback loops that optimize signaling amplitude and timing. We demonstrate that the Ste5 scaffold protein can be used as a platform to systematically reshape output of the yeast mating MAP kinase pathway. We constructed synthetic positive- and negative-feedback loops by dynamically regulating recruitment of pathway modulators to an artificial binding site on Ste5. These engineered circuits yielded diverse behaviors: ultrasensitive dose response, accelerated or delayed response times, and tunable adaptation. Protein scaffolds provide a flexible platform for reprogramming cellular responses and could be exploited to engineer cells with novel therapeutic and biotechnological functions. 相似文献
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Gene regulation at the single-cell level 总被引：1，自引：0，他引：1
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In bacteria, the rate of cell proliferation and the level of gene expression are intimately intertwined. Elucidating these relations is important both for understanding the physiological functions of endogenous genetic circuits and for designing robust synthetic systems. We describe a phenomenological study that reveals intrinsic constraints governing the allocation of resources toward protein synthesis and other aspects of cell growth. A theory incorporating these constraints can accurately predict how cell proliferation and gene expression affect one another, quantitatively accounting for the effect of translation-inhibiting antibiotics on gene expression and the effect of gratuitous protein expression on cell growth. The use of such empirical relations, analogous to phenomenological laws, may facilitate our understanding and manipulation of complex biological systems before underlying regulatory circuits are elucidated. 相似文献
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Design and synthesis of a mimetic from an antibody complementarity-determining region 总被引：8，自引：0，他引：8
H U Saragovi D Fitzpatrick A Raktabutr H Nakanishi M Kahn M I Greene 《Science (New York, N.Y.)》1991,253(5021):792-795
A technique for producing non-peptide compounds (mimetics) of designed specificities was developed that permitted the synthesis of a conformationally restricted molecule that mimicked the binding and functional properties of monoclonal antibody (MAb) 87.92.6, which recognizes the reovirus type 3 cellular receptor. Binding of either MAb 87.92.6, peptide analogs, or 87.1-mimetic to the cellular receptor inhibited cellular proliferation. The mimetic was a synthetic beta-loop structure that mimics the second complementarity-determining region of the MAb. These studies may lead to strategies for the synthetic design of antibody complementarity regions, ligands, and other pharmacologically active agents that are water soluble, resistant to proteolysis, and nonimmunogenic. 相似文献
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Janes KA Albeck JG Gaudet S Sorger PK Lauffenburger DA Yaffe MB 《Science (New York, N.Y.)》2005,310(5754):1646-1653
Signal transduction pathways control cellular responses to stimuli, but it is unclear how molecular information is processed as a network. We constructed a systems model of 7980 intracellular signaling events that directly links measurements to 1440 response outputs associated with apoptosis. The model accurately predicted multiple time-dependent apoptotic responses induced by a combination of the death-inducing cytokine tumor necrosis factor with the prosurvival factors epidermal growth factor and insulin. By capturing the role of unsuspected autocrine circuits activated by transforming growth factor-alpha and interleukin-1alpha, the model revealed new molecular mechanisms connecting signaling to apoptosis. The model derived two groupings of intracellular signals that constitute fundamental dimensions (molecular "basis axes") within the apoptotic signaling network. Projection along these axes captures the entire measured apoptotic network, suggesting that cell survival is determined by signaling through this canonical basis set. 相似文献
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Computing with neural circuits: a model 总被引：46，自引：0，他引：46
A new conceptual framework and a minimization principle together provide an understanding of computation in model neural circuits. The circuits consist of nonlinear graded-response model neurons organized into networks with effectively symmetric synaptic connections. The neurons represent an approximation to biological neurons in which a simplified set of important computational properties is retained. Complex circuits solving problems similar to those essential in biology can be analyzed and understood without the need to follow the circuit dynamics in detail. Implementation of the model with electronic devices will provide a class of electronic circuits of novel form and function. 相似文献
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作物育种正在从传统的经验育种转向BT+IT驱动的智能设计育种。提升智能设计育种的能力和水平对解决我国未来粮食安全问题具有重要意义。未来作物智能设计育种将具有“双轮驱动”特征：智能化的杂交育种以育种大数据和育种模型为基础,精准设计自然变异的最优组合,并以最快捷的杂交组配方式实现自然变异的最优组合;智能化的生物育种利用人工智能技术和合成进化技术,设计DNA/蛋白质序列,可以“道法自然、超越自然”,指导作物的基因编辑育种和合成生物学。探讨了作物智能设计育种范式的理论基础、技术手段和发展趋势,分析了我国作物智能设计育种在产业化过程中面临的市场和政策瓶颈,并提出相关对策。 相似文献
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Sculpting horizons in organic chemistry 总被引：1，自引：0，他引：1
B M Trost 《Science (New York, N.Y.)》1985,227(4689):908-916
Organic chemistry as a discipline derives from and impacts on the biological and abiological world in which we live. Its challenges lie in the areas of structure, reactivity, techniques, and concepts. Powerful structural tools reveal structures from biology that range from control of insect development and behavior to whole new metabolic pathways in humans. Unnatural products create beautiful new molecular shapes whose properties cannot be predicted as well as catalysts that function with enzyme-like control. From structure flows reactivity. Exploration of known reactions points to new directions, and development of new reactions offers the opportunity of streamlined synthetic design. Emerging new techniques offer new dimensions for performing and studying reactions as well as the hope for developing new ones. Merging disparate facts into unified concepts increases predictive capabilities. The extraordinary difficulty of finding the resultant of many small effects may obscure the presence of general theories, creates the art in the practice of the science, and challenges the practitioner. From these general themes derives the quest for selectivity--chemo-, regio-, diastereo-, and enantio-. An examination of the fundamental underpinnings of the applications of organic chemistry reveals that, while impressive strides have been made, the science is best described as being between infancy and childhood. The cross-fertilization between organic chemistry and molecular biology vividly illustrates a merging of chemistry and biology. 相似文献
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