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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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VIII. Earth Earns: An Open Participatory Earthropocene to Astropocene CoCreative Future

2. Second Genesis: Sentient LifeKinder Transitions to a New Intentional, BioGenetic Questiny

Pascalie, Jonathan, et al. Developmental Design of Synthetic Bacterial Architectures by Morphogenetic Engineering. ACS Synthetic Biology. Online May, 2016. A French theorist team including Rene Doursat continues their project to commence not only a genomics revolution, but a second genesis of an organismic anatomy and physiology so as to facilitate and develop improved, healthy, enhanced, intentional creaturely beings liberated from contingent evolutionary tinkering.

Peccoud, Jean. Synthetic Biology: Fostering the Cyber-Biological Revolution. Synthetic Biology. 1/1, 2016. This is an introductory article for this new online Oxford University Press journal by its Editor, the Colorado State University professor of chemical and Biological Engineering.

Since the description, in 2000, of two artificial gene networks, synthetic biology has emerged as a new engineering discipline that catalyzes a change of culture in the life sciences. Recombinant DNA can now be fabricated rather than cloned. Instead of focusing on the development of ad-hoc assembly strategies, molecular biologists can outsource the fabrication of synthetic DNA molecules to a network of DNA foundries. Model-driven product development cycles that clearly identify design, build, and test phases are becoming as common in the life sciences as they have been in other engineering fields. A movement of citizen scientists with roots in community labs throughout the world is trying to democratize genetic engineering. It challenges the life science establishment just like visionaries in the 70s advocated that computing should be personal at a time when access to computers was mostly the privilege of government scientists. Synthetic biology is a cultural revolution that will have far reaching implications for the biotechnology industry. The work of synthetic biologists today prefigures a new generation of cyber-biological systems that may to lead to the 5th industrial revolution. (Abstract)

Polka, Jessica, et al. Building Spatial Synthetic Biology with Compartments, Scaffolds, and Communities. Cold Spring Harbor Perspectives in Biology. 8/8, 2016. Harvard Medical School systems biologists Polka, Stephanie Hays, and Pamela Silver advance nature’s intentional recreation by novel inclusions of these consistent, organizational formations.

Traditional views of synthetic biology often treat the cell as an unstructured container in which biological reactions proceed uniformly. In reality, the organization of biological molecules has profound effects on cellular function: not only metabolic, but also physical and mechanical. Here, we discuss a variety of perturbations available to biologists in controlling protein, nucleotide, and membrane localization. These range from simple tags, fusions, and scaffolds to heterologous expression of compartments and other structures that confer unique physical properties to cells. Next, we relate these principles to those guiding the spatial environments outside of cells such as the extracellular matrix. Finally, we discuss new directions in building intercellular organizations to create novel symbioses. (Abstract)

Symbiotic consortia appeal to engineers for two reasons: (1) division of labor lends itself well to modularity, and (2) it is widely believed that consortia are more stable than mono-
cultures. In this vein, synthetic biologists have engineered consortia made up of different
strains of the same organism, as well as symbioses involving multiple species. (11)

Porcar, Manuel. The Hidden Charm of Life. Life. 9/1, 2019. An entry by a University of Valencia, Spain integrative biologist for a Synthetic Biology from Living Computers to Terraformation issue, see Jamie Davies herein for more. It begins by noting a present metaphor mix of machine and organic analogies and metaphors that it would do well going forward. As an example, “factory” is often applied to cellular metabolism. See also Is Research on Synthetic Cells Moving to the Next Level? by Pasquale Stano in this issue for another take.

Synthetic biology is an engineering view on biotechnology, which has revolutionized genetic engineering. The field has seen a constant development of metaphors that tend to highlight the similarities of cells with machines. I argue here that living organisms, particularly bacterial cells, are not machine-like, engineerable entities, but, instead, factory-like complex systems shaped by evolution. A change of the comparative paradigm in synthetic biology from machines to factories, from hardware to software, and from informatics to economy is discussed. (Abstract)

Porcar, Manuel and Jorge Pereto. Nature versus Design: Synthetic Biology or How to Build a Biological Non-Machine. Integrative Biology. 8/451, 2016. We note this contribution by University of Valencia, Spain, systems biologists because it emphasizes that organisms are not machines. Life has internal causes and purposes aided by resilient modules and redundancies, it is not made or moved by external ways. In regard, this novel field ought not tend to make organic forms and ways more mechanical, rather it should proceed toward a more life-like artificial environment, broadly conceived. See also in this issue A Morphospace for Synthetic Organs and Organoids by Aina Olli-Vila, et al (8/485) and Build to Understand: Synthetic Approaches to Biology by Le-Zhi Wang, et al (8/394). OK

Porcar, Manuel, et al. The Ten Grand Challenges of Synthetic Life. Systems and Synthetic Biology. 5/1-2, 2011. In this new journal for the most major evolutionary transition, as vast possibilities open, senior researchers and proponents including Antoine Danchin, Steen Rasmussen, Andres Moya, and others, from Spain, France, Germany, England, and Denmark to Santa Fe, New Mexico, scope out various lineaments at this early advent so as to better guide, focus, communicate, and safely, respectfully, avail.

Qiu, Yuchi, et al. Cluster Learning-Assisted Directed Evolution. Nature Computational Science. December, 2021. We cite this entry by Michigan State University biochemists as an example among many similar endeavors as our worldwide intellect proceeds to revise and enhance life’s biological composition going forward. For another instance, see AI Revolutions in Biology by Anatassis Perrakis and Titia Sixma in EMBO Reports (22/e54046, 2021.)

A directed evolution as a strategy for protein engineering is presently difficult to do. Machine learning-assisted directed evolution (MLDE), which screens sequence properties in silico, can optimize and reduce the experimental burden. This work introduces an MLDE method along with cluster learning-assisted directed evolution (CLADE). By screening 480 sequences out of 160,000 in a four-site combinatorial library, CLADE achieves global maximal fitness hit rates of up to 91.0%.

Rabinowitch, Ithai. What Would a Synthetic Connectome Look Like? Physics of Life Reviews. Online July 2, 2019. A Hebrew University of Jerusalem senior medical neurobiologist broaches an initial consideration of how collective human programs might carry forth the formative principles of our own brains, as we have just learned, into new, and improved cerebral procreations. The essay ranges from neural and genetic bases to ethical issues, within a sense that this endemic inter-relational quality is a distinctive feature.

A major challenge of contemporary neuroscience is to unravel the structure of the connectome, the ensemble of neural connections between different functional units of the brain, and to reveal how this structure relates to brain function. The synthetic biology approach comprises the assembly of new biological systems out of elementary biological parts, which is dubbed forward-engineering. The rationale is that building a system can be a good way to gain understandings of how that system works. As the fields of connectomics and synthetic biology are independently growing, I propose to beneficially combine them to create synthetic connectomics. This union could be a unifying platform for unraveling the complexities of brain operation and could provide an opportunity for empirically exploring theoretical predictions about network function. (Abstract excerpt)

Rampioni, Giordano, et al. A Synthetic Biology Approach to Bio-Chem-ICT: First Moves Towards Chemical Communication Between Synthetic and Natural Cells. Natural Computing. Online May, 2014. We select this paper among many as an example that theories and projects to commence a second nature via informed human intention might help explain how life began and arose in the first place. Italian systems biologists including Luisa Damaino go on to convey, as common today, how biology and evolution is better understood from substantial matter to cellular beings, universe to us, in terms of informational-computational phenomena and programs. This course is said to reflect every organism’s innate autopoietic autonomy, which we scientists might now respectfully appreciate, continue and enhance.

Ravoo, Bart. Frontiers of Molecular Self-Assembly. Israel Journal of Chemistry. 59/868, 2019. An introduction to a special issue on this active global research endeavor to realize, and implement nature’s own deep propensity to organize, vivify and autocreate itself. Some papers are Self-Sorting in Supramolecular Assembly, Dissipative Self-Assembly of Peptides, and From Discrete Structures to Biomimetic Materials.

Renata, Hans, et al. Expanding the Enzyme Universe: Accessing Non-Natural Reactions by Mechanism-Guided Directed Evolution. Angewandte Chemie International Edition. 54/3351, 2015. California Institute of Technology chemical engineers Renate, Jane Wang, and Frances Arnold continue their project (see Arnold Lab publications) to learn how living systems became vitally complex so as to initiate a biomimetic palliative and sustainable phase. See also, for example, The Nature of Chemical Innovation: New Enzymes by Evolution by Frances Arnold in Quarterly Reviews of Biophysics (48/404, 2015).

High selectivity and exquisite control over the outcome of reactions entice chemists to use biocatalysts in organic synthesis. However, many useful reactions are not accessible because they are not in nature’s known repertoire. In this Review, we outline an evolutionary approach to engineering enzymes to catalyze reactions not found in nature. We begin with examples of how nature has discovered new catalytic functions and how such evolutionary progression has been recapitulated in the laboratory starting from extant enzymes. We then examine non-native enzyme activities that have been exploited for chemical synthesis, with an emphasis on reactions that do not have natural counterparts. Non-natural activities can be improved by directed evolution, thus mimicking the process used by nature to create new catalysts. Finally, we describe the discovery of non-native catalytic functions that may provide future opportunities for the expansion of the enzyme universe. (Abstract)

Enzyme: Any of numerous proteins produced in living cells that accelerate or catalyze the metabolic processes of an organism. a substance produced by a living organism that acts as a catalyst to bring about a specific biochemical reaction.

Ronquist, Scott, et al. Algorithm for Cellular Reprogramming. Proceedings of the National Academy of Sciences. 114/11832, 2017. A ten person interdisciplinary team from the University of Michigan, University of Maryland, Harvard University and IXL Learning, Raleigh, NC provide a microcosm of the frontier abilities of genomic and biological research. As the quote cites, a radical new phase is respectfully beginning to take over living systems for all manner of curative benefits and enhancements. This capacity involves “a dynamic systems view of the genome” so as to achieve an intentional employ of nature’s independent, universal source code.

Reprogramming the human genome toward any desirable state is within reach; application of select transcription factors drives cell types toward different lineages in many settings. We introduce the concept of data-guided control in building a universal algorithm for directly reprogramming any human cell type into any other type. Our algorithm is based on time series genome transcription and architecture data and known regulatory activities of transcription factors, with natural dimension reduction using genome architectural features. Our algorithm predicts known reprogramming factors, top candidates for new settings, and ideal timing for application of transcription factors. This framework can be used to develop strategies for tissue regeneration, cancer cell reprogramming, and control of dynamical systems beyond cell biology. (Significance)

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