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Modelling co-translational dimerization for programmable nonlinearity in synthetic biology
No full text8 Pág.Nonlinearity plays a fundamental role in the performance of both natural and synthetic biological networks. Key functional motifs in living microbial systems, such as the emergence of bistability or oscillations, rely on nonlinear molecular dynamics. Despite its core importance, the rational design of nonlinearity remains an unmet challenge. This is largely due to a lack of mathematical modelling that accounts for the mechanistic basis of nonlinearity. We introduce a model for gene regulatory circuits that explicitly simulates protein dimerization-a well-known source of nonlinear dynamics. Specifically, our approach focuses on modelling co-translational dimerization: the formation of protein dimers during-and not after-translation. This is in contrast to the prevailing assumption that dimer generation is only viable between freely diffusing monomers (i.e. post-translational dimerization). We provide a method for fine-tuning nonlinearity on demand by balancing the impact of co- versus post-translational dimerization. Furthermore, we suggest design rules, such as protein length or physical separation between genes, that may be used to adjust dimerization dynamics in vivo. The design, build and test of genetic circuits with on-demand nonlinear dynamics will greatly improve the programmability of synthetic biological systems.This work was supported by the SynBio3D project of the UK Engineering and Physical Sciences Research Council (EP/R019002/1) and the European CSA on biological standardization BIOROBOOST (EU grant no. 820699). Á.G.-M. was also supported by grants from Comunidad de Madrid (Atraccion de Talento Program, grant no. 2019-T1/BIO-14053) and the Severo Ochoa Program for Centres of Excellence in R&D from the Agencia Estatal de Investigacion of Spain, grant no. SEV-2016-0672 (2017–2021).Peer reviewe
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Pathways to cellular supremacy in biocomputing
No full textAbstract
Synthetic biology uses living cells as the substrate for performing human-defined computations. Many current implementations of cellular computing are based on the “genetic circuit” metaphor, an approximation of the operation of silicon-based computers. Although this conceptual mapping has been relatively successful, we argue that it fundamentally limits the types of computation that may be engineered inside the cell, and fails to exploit the rich and diverse functionality available in natural living systems. We propose the notion of “cellular supremacy” to focus attention on domains in which biocomputing might offer superior performance over traditional computers. We consider potential pathways toward cellular supremacy, and suggest application areas in which it may be found
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Spatial modelling of transcription dynamics in bacterial gene regulatory networks
Get PDFPh. D. Thesis.In Synthetic biology, researchers can alter the DNA sequence of organisms such
that the behaviour to specific inputs is predictable. Regulatory systems have been
‘hacked’ into doing computation, help with bio-production, aid in personalised
medicine and providing highly specific sensors.
A major bottleneck in current synthetic biology is that models fail to predict
system behaviour reliably, causing recent progress to be reliant on the trial and
error of model-assisted system designs.
One of the reasons for the models to fail is the neglect of Spatial effects. While
this neglect simplifies models, recent experimental data shows localised effects.
This work shows that only the combination of 3D cytosol diffusion and the
1D sliding along the chromosome of transcription factors can explain localised
effects; the modelling transcription factors initial sliding route after formation
reproduces experimental results.
However, one essential assumption for the model described above is the initial
location of a functional transcription factor at the encoding gene. While the
coupled transcription and translation in prokaryotes are experimentally verified
and can lead to the localisation of Transcription Factor proteins, this localisation
must be assumed to be transferred to the active dimer form to reproduce the
experiment.
To substantiate this assumption, this work expands the limited field of protein
dimerisation. A new model is introduced to explain the localisation effect with
an extra pathway we call Translation Mediated Dimerisation. Here, the partially
formed transcription factors still undergoing translation are thought to meet and
form a dimer while still constrained to the mRNA on the other end. Even if this
occurs in a minority of events, this can drastically affect non-linear behaviour.
This model allows utilisation of localised effects for the rational design of
system dynamics otherwise unavailable, expanding the possibilities and increasing
the efficiency of synthetic biolog
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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