scholarly journals A Prototype for Modular Cell Engineering

2017 ◽  
Author(s):  
Brandon Wilbanks ◽  
Donovan S. Layton ◽  
Sergio Garcia ◽  
Cong T. Trinh

ABSTRACTWhen aiming to produce a target chemical at high yield, titer, and productivity, various combinations of genetic parts available to build the target pathway can generate a large number of strains for characterization. This engineering approach will become increasingly laborious and expensive when seeking to develop desirable strains for optimal production of a large space of biochemicals due to extensive screening. Our recent theoretical development of modular cell (MODCELL) design principles can offer a promising solution for rapid generation of optimal strains by coupling a modular cell and exchangeable production modules in a plug-and-play fashion. In this study, we experimentally validated some designed properties of MODCELL by demonstrating: i) a modular (chassis) cell is required to couple with a production module, a heterologous ethanol pathway, as a testbed, ii) degree of coupling between the modular cell and production modules can be modulated to enhance growth and product synthesis, iii) a modular cell can be used as a host to select an optimal pyruvate decarboxylase (PDC) of the ethanol production module and to help identify a hypothetical PDC protein, and iv) adaptive laboratory evolution based on growth selection of the modular cell can enhance growth and product synthesis rates. We envision that the MODCELL design provides a powerful prototype for modular cell engineering to rapidly create optimal strains for synthesis of a large space of biochemicals.

2018 ◽  
Author(s):  
Sergio Garcia ◽  
Cong T. Trinh

ABSTRACTDiversity of cellular metabolism can be harnessed to produce a large space of molecules. However, development of optimal strains with high product titers, rates, and yields required for industrial production is laborious and expensive. To accelerate the strain engineering process, we have recently introduced a modular cell design concept that enables rapid generation of optimal production strains by systematically assembling a modular cell with an exchangeable production module(s) to produce target molecules efficiently. In this study, we formulated the modular cell design concept as a general multiobjective optimization problem with flexible design objectives derived from mass action. We developed algorithms and an associated software package, named ModCell2 to implement the design. We demonstrated that ModCell2 can systematically identify genetic modifications to design modular cells that can couple with a variety of production modules and exhibit a minimal tradeoff among modularity, performance, and robustness. Analysis of the modular cell designs revealed both intuitive and complex metabolic architectures enabling modular production of these molecules. We envision ModCell2 provides a powerful tool to guide modular cell engineering and sheds light on modular design principles of biological systems.


1999 ◽  
Vol 20 (1) ◽  
pp. 5-26
Author(s):  
Henk Flap

A recent theoretical development within the social sciences has been the emergence of the social capital research program. This is a program on relational resources, their creation, use. and effects. It took shape first within sociology and anthropology, nowadays it is also growing in popularity within political sciences and economics.


2013 ◽  
Vol 11 (2) ◽  
pp. 417-432 ◽  
Author(s):  
Alan Cienki

Image schemas have been a fundamental construct in cognitive linguistics, providing grounds for psychological, philosophical, as well as linguistic research. Given the focus in cognitive linguistics on embodied experience as a fundamental basis for language structure and meaning, the employment of image schemas in the analysis of gesture with speech is a logical extension. However, given their level of abstraction, to what degree do image schemas provide a useful explanatory tool for researching the concrete, physically embodied details of gestures? This article considers the answer to this question and then turns to a more recent theoretical development that complements the picture by encompassing a different realm of cognitive and linguistic phenomena. This research, on ‘mimetic schemas’, is shown to have great potential for thinking about some known phenomena of gesture in a new way. Schema research on these different levels thus provides a useful means to analyze behavior in another modality involved in spoken language use, namely the visual.


2015 ◽  
Vol 44 (2) ◽  
pp. 286-307 ◽  
Author(s):  
Kristina Schoemmel ◽  
Thomas Skriver Jønsson ◽  
Hans-Jeppe Jeppesen

Purpose – In order to contribute to the understanding of affective commitment towards distinct workplace targets, the purpose of this paper is to develop and validate a Multitarget Affective Commitment Scale (MACS) through two data collections. The MACS uses similarly worded items for distinct targets and reflects the most recent theoretical development of affective commitment. Design/methodology/approach – In the first data collection, items from previous commitment scales were tested through the social network service Facebook (n=305). The second data collection was conducted in the healthcare system of Denmark (n=496) using survey questionnaires. Findings – In Study 1, exploratory factor analyses were conducted to reduce the items based on the Facebook data. In Study 2, the authors confirm the findings of Study 1 and further reduce the items based on the healthcare sample. The healthcare sample is also used in Study 3, where the authors validate the MACS by investigating its relationship with predictors, correlates, and outcomes. Originality/value – The results suggest that the MACS are a reliable and valid measure of affective commitment compatible with the diverse targets to which affective commitment often occurs. Consequently, the MACS is applicable for research investigating multiply affective commitments, thereby advancing the understanding of interactions between affective commitments and diverse targets, among other applications.


2001 ◽  
Vol 67 (12) ◽  
pp. 5621-5625 ◽  
Author(s):  
Michele M. Bianchi ◽  
Luca Brambilla ◽  
Francesca Protani ◽  
Chi-Li Liu ◽  
Jefferson Lievense ◽  
...  

ABSTRACT A high yield of lactic acid per gram of glucose consumed and the absence of additional metabolites in the fermentation broth are two important goals of lactic acid production by microrganisms. Both purposes have been previously approached by using aKluyveromyces lactis yeast strain lacking the single pyruvate decarboxylase gene (KlPDC1) and transformed with the heterologous lactate dehydrogenase gene (LDH). The LDH gene was placed under the control theKlPDC1 promoter, which has allowed very high levels of lactate dehydrogenase (LDH) activity, due to the absence of autoregulation by KlPdc1p. The maximal yield obtained was 0.58 g g−1, suggesting that a large fraction of the glucose consumed was not converted into pyruvate. In a different attempt to redirect pyruvate flux toward homolactic fermentation, we usedK. lactis LDH transformant strains deleted of the pyruvate dehydrogenase (PDH) E1α subunit gene. A great process improvement was obtained by the use of producing strains lacking both PDH and pyruvate decarboxylase activities, which showed yield levels of as high as 0.85 g g−1 (maximum theoretical yield, 1 g g−1), and with high LDH activity.


2021 ◽  
Vol 2(26) ◽  
pp. 208-222
Author(s):  
I.V. Stavtzeva ◽  
◽  
N.A. Yegorova ◽  

Clary sage (Salvia sclarea L.) is a widely demanded essential oil plant. The products of its processing are used in medicine, perfumery and cosmetics, food industry, paint and varnish production. The main breeding tasks are to develop cultivars that combine high yield and quality of essential oil, resistant to abiotic and biotic stresses. All clary sage cultivars registered in the ‘State register of breeding achievements allowed for use’ Russian Federation were obtained on the basis of traditional methods. The initial breeding material of S. sclarea was obtained at the FSBSI “Research Institute of Agriculture of Crimea” using methods of cell engineering (induction of somaclones from callus cultures, obtaining hybrids in embryoculture and cell selection for resistance to osmotic stress). The aim of this work was to study the main economic and morphometric parameters of clary sage samples created using various biotechnological methods at the main stages of the breeding process. As a material for research, we used samples obtained in vitro using three biotechnological methods – regenerants (R2-R3) from calli of ‘C-785’ and ‘Taigan’ cultivars, obtained in isolated embryo culture hybrids (Salvia sclarea L. x S. grandiflora Etling.) and forms selected in embryoculture on a selective medium with an osmotic (mannitol or NaCl). When studying 10 sage samples (seed progeny of regenerants) in the breeding nursery (2012–2014), three that exceeded the control cultivar ‘Taigan’ in terms of basic economic characteristics were identified. The collection of essential oil from them was 1.2-1.4 times higher than in the control. In the nursery of competitive variety trials (2016–2019), when studying three samples (No. R3-1-6, 226-08 and 1-01), No. R3-1-6 was selected for a number of indicators. This sample is seed progeny of regenerant obtained by the induction of morphogenesis from callus. A characteristic feature of this sample was an increase in the number of lateral shoots per inflorescence by 41.1 %, which contributed to an increase in the mass of inflorescences. By the yield of inflorescences (162.0 c/ha) and the collection of essential oil (51.5 kg/ha), No. R3-1-6 exceeded control by 24.9 % and 43.9 %, respectively. The patent on the new clary sage cultivar ‘Selinzh’ (No. R3-1-6), in the creation of which the method of cell engineering was used for the first time, was received.


2002 ◽  
Vol 01 (01) ◽  
pp. 225-244 ◽  
Author(s):  
YI JING YAN ◽  
HOUYU ZHANG

This article reviews our recent theoretical development toward understanding the interplay of electronic structure and dephasing effects on charge transfer/transport through molecular donor-bridge-acceptor systems. Both the generalized scattering matrix and Green's function formalisms for partially incoherent tunneling processes are summarized. Presented is also an exact mapping between the kinetic rate constants and the electric conductances in evaluation of chemical yields of sequential charge transfer in the presence of competing branching reactions. As an important example, the mechanism of long-range charge transfer in DNA in aqueous solution is investigated with a quantum chemistry implementation of the generalized Green's function formalism. A time scale of about 5 ps is found for the partially incoherent tunneling through a thymine/adenine π-stack in DNA. Numerical results further show that while the carrier oxidative charge does hop sequentially over all guanine sites in a DNA duplex, its tunneling over thymine/adenine bridge base pairs deviates substantially from the superexchange regime. Presented are also evidences for the involvement of both intrastrand and interstrand pathways in the ground state hole charge transfer in DNA.


2008 ◽  
Vol 22 (01n02) ◽  
pp. 94-103 ◽  
Author(s):  
FU-CHUN ZHANG ◽  
SHUN-QING SHEN

A brief review is presented on the resonant spin Hall effect, where a tiny external electric field induces a saturated spin Hall current in a 2-dimensional electron or hole gas in a perpendicular magnetic field. The phenomenon is attributed to the energy level crossing associated with the spin-orbit coupling and the Zeeman splitting. We summarize recent theoretical development of the effect in various systems and discuss possible experiments to observe the effect.


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