Bottom-Up Synthetic Biology: Engineering in a Tinkerer’s World

Science ◽  
2011 ◽  
Vol 333 (6047) ◽  
pp. 1252-1254 ◽  
Author(s):  
Petra Schwille

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.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lorenzo Olivi ◽  
Mareike Berger ◽  
Ramon N. P. Creyghton ◽  
Nicola De Franceschi ◽  
Cees Dekker ◽  
...  

AbstractRecent developments in synthetic biology may bring the bottom-up generation of a synthetic cell within reach. A key feature of a living synthetic cell is a functional cell cycle, in which DNA replication and segregation as well as cell growth and division are well integrated. Here, we describe different approaches to recreate these processes in a synthetic cell, based on natural systems and/or synthetic alternatives. Although some individual machineries have recently been established, their integration and control in a synthetic cell cycle remain to be addressed. In this Perspective, we discuss potential paths towards an integrated synthetic cell cycle.


2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Brian R. Fritz ◽  
Laura E. Timmerman ◽  
Nichole M. Daringer ◽  
Joshua N. Leonard ◽  
Michael C. Jewett

Synthetic biology is a nascent technical discipline that seeks to enable the design and construction of novel biological systems to meet pressing societal needs. However, engineering biology still requires much trial and error because we lack effective approaches for connecting basic “parts” into higher-order networks that behave as predicted. Developing strategies for improving the performance and sophistication of our designs is informed by two overarching perspectives: “bottom-up” and “top-down” considerations. Using this framework, we describe a conceptual model for developing novel biological systems that function and interact with existing biological components in a predictable fashion. We discuss this model in the context of three topical areas: biochemical transformations, cellular devices and therapeutics, and approaches that expand the chemistry of life. Ten years after the construction of synthetic biology's first devices, the drive to look beyond what does exist to what can exist is ushering in an era of biology by design.


2013 ◽  
Vol 41 (5) ◽  
pp. 1159-1165 ◽  
Author(s):  
Shiksha Mantri ◽  
K. Tanuj Sapra

Realization of a functional artificial cell, the so-called protocell, is a major challenge posed by synthetic biology. A subsequent goal is to use the protocellular units for the bottom-up assembly of prototissues. There is, however, a looming chasm in our knowledge between protocells and prototissues. In the present paper, we give a brief overview of the work on protocells to date, followed by a discussion on the rational design of key structural elements specific to linking two protocellular bilayers. We propose that designing synthetic parts capable of simultaneous insertion into two bilayers may be crucial in the hierarchical assembly of protocells into a functional prototissue.


2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Simon Bachler ◽  
Dominik Haidas ◽  
Marion Ort ◽  
Todd A. Duncombe ◽  
Petra S. Dittrich

AbstractIn the field of bottom-up synthetic biology, lipid membranes are the scaffold to create minimal cells and mimic reactions and processes at or across the membrane. In this context, we employ here a versatile microfluidic platform that enables precise positioning of nanoliter droplets with user-specified lipid compositions and in a defined pattern. Adjacent droplets make contact and form a droplet interface bilayer to simulate cellular membranes. Translocation of molecules across membranes are tailored by the addition of alpha-hemolysin to selected droplets. Moreover, we developed a protocol to analyze the translocation of non-fluorescent molecules between droplets with mass spectrometry. Our method is capable of automated formation of one- and two-dimensional droplet networks, which we demonstrated by connecting droplets containing different compound and enzyme solutions to perform translocation experiments and a multistep enzymatic cascade reaction across the droplet network. Our platform opens doors for creating complex artificial systems for bottom-up synthetic biology.


2018 ◽  
Vol 5 (4) ◽  
pp. 110 ◽  
Author(s):  
Kazusa Beppu ◽  
Ziane Izri ◽  
Yusuke Maeda ◽  
Ryota Sakamoto

As expressed “God made the bulk; the surface was invented by the devil” by W. Pauli, the surface has remarkable properties because broken symmetry in surface alters the material properties. In biological systems, the smallest functional and structural unit, which has a functional bulk space enclosed by a thin interface, is a cell. Cells contain inner cytosolic soup in which genetic information stored in DNA can be expressed through transcription (TX) and translation (TL). The exploration of cell-sized confinement has been recently investigated by using micron-scale droplets and microfluidic devices. In the first part of this review article, we describe recent developments of cell-free bioreactors where bacterial TX-TL machinery and DNA are encapsulated in these cell-sized compartments. Since synthetic biology and microfluidics meet toward the bottom-up assembly of cell-free bioreactors, the interplay between cellular geometry and TX-TL advances better control of biological structure and dynamics in vitro system. Furthermore, biological systems that show self-organization in confined space are not limited to a single cell, but are also involved in the collective behavior of motile cells, named active matter. In the second part, we describe recent studies where collectively ordered patterns of active matter, from bacterial suspensions to active cytoskeleton, are self-organized. Since geometry and topology are vital concepts to understand the ordered phase of active matter, a microfluidic device with designed compartments allows one to explore geometric principles behind self-organization across the molecular scale to cellular scale. Finally, we discuss the future perspectives of a microfluidic approach to explore the further understanding of biological systems from geometric and topological aspects.


2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Fengyu Zhang ◽  
Yanhong Sun ◽  
Yihao Zhang ◽  
Wenting Shen ◽  
Shujing Wang ◽  
...  

AbstractSynthetic Biology aims to create predictable biological circuits and fully operational biological systems. Although there are methods to create more stable oscillators, such as repressilators, independently controlling the oscillation of reporter genes in terms of their amplitude and period is only on theoretical level. Here, we introduce a new oscillator circuit that can be independently controlled by two inducers in Escherichia coli. Some control components, including σECF11 and NahR, were added to the circuit. By systematically tuning the concentration of the inducers, salicylate and IPTG, the amplitude and period can be modulated independently. Furthermore, we constructed a quantitative model to forecast the regulation results. Under the guidance of the model, the expected oscillation can be regulated by choosing the proper concentration combinations of inducers. In summary, our work achieved independent control of the oscillator circuit, which allows the oscillator to be modularized and used in more complex circuit designs.


2016 ◽  
Vol 87 (2) ◽  
pp. 02C107 ◽  
Author(s):  
A. Kitagawa ◽  
A. G. Drentje ◽  
T. Fujita ◽  
M. Muramatsu ◽  
K. Fukushima ◽  
...  

2017 ◽  
Vol 1 (3) ◽  
pp. 241-243
Author(s):  
Jeffrey Skolnick

As is typical of contemporary cutting-edge interdisciplinary fields, computational biology touches and impacts many disciplines ranging from fundamental studies in the areas of genomics, proteomics transcriptomics, lipidomics to practical applications such as personalized medicine, drug discovery, and synthetic biology. This editorial examines the multifaceted role computational biology plays. Using the tools of deep learning, it can make powerful predictions of many biological variables, which may not provide a deep understanding of what factors contribute to the phenomena. Alternatively, it can provide the how and the why of biological processes. Most importantly, it can help guide and interpret what experiments and biological systems to study.


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