Autonomous bacterial localization and gene expression based on nearby cell receptor density

Wu, Hsuan‐Chen; Tsao, Chen‐Yu; Quan, David N.; Cheng, Yi; Servinsky, Matthew D.; Carter, Karen K.; Jee, Kathleen; Terrell, Jessica L.; Zargar, Amin; Rubloff, Gary W.; Payne, Gregory F.; Valdés, James J.; Bentley, William E.

doi:10.1038/msb.2012.71

Cited by 67 publications

(66 citation statements)

References 50 publications

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“…This scenario evokes consideration of the potentially disparate dynamics of AI-2 diffusion, AI-2-mediated cell motility and AI-2-mediated gene expression, as well as the different length scales involved. Similar concepts were reported previously using a synthetic system for AI-2 production (Wu et al, 2013). In that work, AI-2 signal molecules were generated in situ on the surface of cancer cells by the assembly of its synthases onto epidermal growth factor receptor (EGFR) surface receptors and with supplementation of the AI-2 precursor S-adenosylhomocysteine to the media.…”

Section: Applications and Further Insights-a Call To Arms?mentioning

confidence: 55%

“…Our data, which suggest that sensor cells respond to AI-2 by initiating DsRed expression at slightly different times and at slightly different rates, point to a 4-5 h 'focusing' of the overall population while leading to the quantized quorum. That is, QS can function as a phenotypic focusing system (Wu et al, 2013), as well as a determinant of collective behavior.…”

Section: Discussionmentioning

confidence: 99%

“…Certainly, among the beneficial phenotypes attributed to QS, which could also be referred to as the 'currency' of the public good, are bioluminescence (Bassler et al, 1994), virulence (Zhu et al, 2002), biofilm formation (Balestrino et al, 2005;Gonzalez Barrios et al, 2006;Li et al, 2007), cell division, motility and cooperativity (Dandekar et al, 2012). We note that intentional rewiring these QS-regulated systems also benefits biotechnological applications, if not the microbes themselves (Fernandes et al, 2010;Tsao et al, 2010;Wu et al, 2013;Swofford et al, 2015;Thompson et al, 2015). It is therefore intriguing to consider what is the particular quorum and why was it reached.…”

Section: Introductionmentioning

confidence: 99%

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Directed assembly of a bacterial quorum

et al. 2015

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Many reports have elucidated the mechanisms and consequences of bacterial quorum sensing (QS), a molecular communication system by which bacterial cells enumerate their cell density and organize collective behavior. In few cases, however, the numbers of bacteria exhibiting this collective behavior have been reported, either as a number concentration or a fraction of the whole. Not all cells in the population, for example, take on the collective phenotype. Thus, the specific attribution of the postulated benefit can remain obscure. This is partly due to our inability to independently assemble a defined quorum, for natural and most artificial systems the quorum itself is a consequence of the biological context (niche and signaling mechanisms). Here, we describe the intentional assembly of quantized quorums. These are made possible by independently engineering the autoinducer signal transduction cascade of Escherichia coli (E. coli) and the sensitivity of detector cells so that upon encountering a particular autoinducer level, a discretized sub-population of cells emerges with the desired phenotype. In our case, the emergent cells all express an equivalent amount of marker protein, DsRed, as an indicator of a specific QS-mediated activity. The process is robust, as detector cells are engineered to target both large and small quorums. The process takes about 6 h, irrespective of quorum level. We demonstrate sensitive detection of autoinducer-2 (AI-2) as an application stemming from quantized quorums. We then demonstrate sub-population partitioning in that AI-2-secreting cells can 'call' groups neighboring cells that 'travel' and establish a QS-mediated phenotype upon reaching the new locale.

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Section: Applications and Further Insights-a Call To Arms?mentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Directed assembly of a bacterial quorum

et al. 2015

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“…We and others (14,15) have developed several applications that exploit swimming and motility functions of bacteria, in particular as a means to deliver therapeutic payloads synthesized by the swimming cells (16,17). We have exploited che mutants (which do not run) to directionally guide cells to specific sites, a phenomenon referred to as pseudotaxis (18,19,20).…”

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confidence: 99%

TumbleScore: Run and Tumble Analysis for Low Frame-Rate Motility Videos

et al. 2017

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Scientists often exploit the motility of peritrichously flagellated bacteria for various applications. A common alteration is modifying the frequency of mid-movement changes in direction, known as tumbles. Such differences in bacterial swimming patterns can prove difficult to quantify, especially for those without access to high-speed optical equipment. Traditionally, scientists have resorted to less accurate techniques, such as soft agar plate assays, or have been forced to invest in costly equipment. Here, we present TumbleScore, software designed to track and quantify bacterial movies with slow, as well as fast, frame-rates. Developed and fully contained within MATLAB, TumbleScore processes motility videos and returns pertinent tumbling metrics, including: () linear speed, () rotational speed, () percentage of angle changes below a given threshold, and () ratio of total path length to Euclidian distance, or arc-chord ratio (ACR). In addition, TumbleScore produces a "rose graph" visualization of bacterial paths. The software was validated using both fabricated and experimental motility videos.

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“…One important application of using synthetic cells as environmental controllers is in therapeutics [19]. Cells have been programmed to detect nearby environmental features and display a phenotypic response [68]. In particular, synthetic cells can localise to the environment of tumours and selectively respond to cancerous cells [69], [70].…”

Section: B Extra-cell Plantmentioning

confidence: 99%

Synthetic biology: A control engineering perspective

Prescott

Papachristodoulou

2014

2014 European Control Conference (ECC)

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Abstract-Synthetic Biology is a new, rapidly developing field at the interface of Engineering and Biology. It aims to design new, or redesign existing biological systems for a particular purpose. The early years have seen the design of simple devices and parts (such as switches and oscillators); Synthetic Biology is now entering a new phase of development as the successfully designed devices of recent years are exploited to create systems of increasing sophistication. Control theoretic techniques play an important part in the design of these networks, as well as for allowing increasing levels of complexity to be engineered into synthetic biological systems. At the same time, the implementation of feedback control in these networks will allow them to sense, process and actuate on environmental and internal cues.

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Autonomous bacterial localization and gene expression based on nearby cell receptor density

Abstract: Escherichia coli were engineered to enable programmed motility, sensing and phenotypic response to the density of epidermal growth factor receptor expressed on the surface of cancer cells.

Cited by 67 publications

References 50 publications

Directed assembly of a bacterial quorum

Directed assembly of a bacterial quorum

TumbleScore: Run and Tumble Analysis for Low Frame-Rate Motility Videos

Synthetic biology: A control engineering perspective

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