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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 Ecosmocene CoCreativity

2. Second Genesis: Emergent LifeKinder Proceeds to an Aware BioGenetic Phase

Bedau, Mark, et al. Living Technology. Artificial Life. 16/1, 2010. With co-authors John McCaskill, Norman Packard, and Steen Rasmussen, whose common link could be the European Center for Living Technology, an entry to leading edges of the mind takeover of matter so as to (re)create and carry forth a better, more organic and humane, civilization.

The concept of living technology—that is, technology that is based on the powerful core features of life—is explained and illustrated with examples from artificial life software, reconfigurable and evolvable hardware, autonomously self-reproducing robots, chemical protocells, and hybrid electronic-chemical systems. We define primary (secondary) living technology according as key material components and core systems are not (are) derived from living organisms. Primary living technology is currently emerging, distinctive, and potentially powerful, motivating this review. We trace living technology's connections with artificial life (soft, hard, and wet), synthetic biology (top-down and bottom-up), and the convergence of nano-, bio-, information, and cognitive (NBIC) technologies. We end with a brief look at the social and ethical questions generated by the prospect of living technology. (89)

Bekiaris, Bekiaris, Pavlos and Steffen Klamt. Designing Microbial Communities to Maximize the Thermodynamic Driving Force for the Production of Chemicals. PLoS Computational Biology. June, 2021. MPI for Dynamics of Complex Technical Systems consider ways to apply our collaborative findings about bacterial composites so as to begin a new phase of intentional formulations for an array of beneficial uses. See also An Evolutionary Algorithm for Designing Microbial Communities via Environmental Modification by Alan Pacheco and Daniel Segre in the Journal of the Royal Society Interface (June 2021).

In this work, we present a new computational method to design synthetic bacterial communities with improved capabilities for the synthesis of desired target metabolites. Our approach takes a constraint-based metabolic model of an organism as input and searches for suitable partitioning pathways such that the thermodynamic driving force for product synthesis is maximized. We tested this approach with a core and with a genome-scale metabolic network model of Escherichia coli. We found that, for dozens of metabolites, there exist communities with dedicated strains of E. coli where the maximal thermodynamic driving force can be enhances. (Summary excerpt)

Despite new understandings of how environmental composition affects microbial communities, how to apply this knowledge to the design of synthetic multispecies consortia remains elusive. Natural microbial communities can harbor thousands of different organisms and environmental substrates, in a vast combinatorial space.. Here, we present a method based on a meld of machine learning and dynamic flux balance analysis that selects optimal environmental compositions to produce target community phenotypes. A genetic algorithm is then used to evaluate the behavior of the community relative to a target phenotype, and subsequently adjust the environment to allow the organisms to more closely approach this target. (Pacheco/Segre excerpt)

Benner, Steven, et al. Alternative Watson-Crick Synthetic Genetic Systems. Cold Spring Harbor Perspectives in Biology. 8/11, 2016. A Foundation for Applied Molecular Evolution, Florida, research team proposes an “artificially expanded genetic information system” AEGIS to begin some 63 years later to wholly rewrite nature’s genome code. The project takes on the guise of preparing a much larger, broadly conceived, edition to inform our novel evolutionary recreation. See also The Need for Integrated Approaches in Metabolic Engineering by Anna Lechner, et al in the same issue (Abstract below).

In its “grand challenge” format in chemistry, “synthesis” as an activity sets out a goal that is substantially beyond current theoretical and technological capabilities. In pursuit of this goal, scientists are forced across uncharted territory, where they must answer unscripted questions and solve unscripted problems, creating new theories and new technologies in ways that would not be created by hypothesis-directed research. Thus, synthesis drives discovery and paradigm changes in ways that analysis cannot. Described here are the products that have arisen so far through the pursuit of one grand challenge in synthetic biology: Recreate the genetics, catalysis, evolution, and adaptation that we value in life, but using genetic and catalytic biopolymers different from those that have been delivered to us by natural history on Earth. The outcomes in technology include new diagnostic tools that have helped personalize the care of hundreds of thousands of patients worldwide. In science, the effort has generated a fundamentally different view of DNA, RNA, and how they work. (Benner Abstract)

This review highlights state-of-the-art procedures for heterologous small-molecule biosynthesis, the associated bottlenecks, and new strategies that have the potential to accelerate future accomplishments in metabolic engineering. We emphasize that a combination of different approaches over multiple time and size scales must be considered for successful pathway engineering in a heterologous host. We have classified these optimization procedures based on the “system” that is being manipulated: transcriptome, translatome, proteome, or reactome. By bridging multiple disciplines, including molecular biology, biochemistry, biophysics, and computational sciences, we can create an integral framework for the discovery and implementation of novel biosynthetic production routes. (Lechner Abstract)

Bhasin, Devesh and Daniel McAdams. The Characterization of Biological Organization, Abstraction and Novelty in Biomimetic Design. Design. 2/4, 2018. In this new MDPI online journal, in a topical Advances in Biologically Inspired Design issue, Texas A&M University engineers at once review prior creativities and solutions of evolutionary nature, so as to intentionally avail and carry forth to a better futurity. See also the MDPI journal Biomimetics which emphasizes more specific examples.

Through a billion year evolution, a latent record of successful and detailed design practices has developed in nature. The endeavors to exploit this resource have resulted in successful products in various fields including, but not limited to, networking, propulsion, surface engineering, and robotics. In this work, a study of existing biomimetic designs has been carried out according to the biological organizational level, the abstraction level, and a novelty measure. Through this review and categorization, we recognize patterns in existing biomimetic and bio-inspired products by analyzing their cross-categorical distribution. Using the distribution, we identify the categories which yield novel bio-inspired designs. (Abstract excerpt)

Biologically-inspired design is a design philosophy that encourages us to learn from nature, and results in the discovery of non-conventional solutions to problems that are often more efficient, economic, and elegant. Taking inspiration from nature has made (and can make) valuable contributions to engineering. In the last few decades, there has been increased attention on the significant technical innovations that can result from biological inspiration. This Special Issue is focused on the techniques, approaches and theories that facilitate biologically inspired design for engineering applications. Manuscript submissions on original research and literature reviews in the areas mentioned as keywords below are highly encouraged. (Issue Proposal)

Bianco, Simone, et al. Towards Computer-aided Design of Cellular Structure. Physical Biology. 17/2, 2020. Center for Cellular Construction researchers (see below) in league with UC Berkeley and UC San Francisco biophysicists including Wallace Marshall scope out this frontier 2020s phase when collective human intellect can begin a new, second, palliative, respectful genesis procreation.

Cells are complex machines with salutary potential for applications in medicine and biotechnology. Although much effort has been devoted to engineering the metabolic, genetic, and signaling pathways of cells, methods for systematically engineering the physical structure of cells are less developed. Here we consider how coarse-grained models for cellular geometry at the organelle level can be used to build computer-aided design (CAD) tools for cellular structure. (Abstract excerpt)

Welcome to the Center for Cellular Construction, an NSF Science and Technology Center. Our mission is to advance cell biology by learning how to engineer the physical structure and interactions of living cells, so they become living bioreactors and modules of novel self-organizing devices. Accomplishing these goals will provide a new basis for tackling important global challenges of the 21st century.

Biondi, Elisa and Steven Benner. Artificially Expanded Genetic Information Systems for New Aptamer Technologies. Biomedicines. 6/2, 2018. It is now known that life’s four letter G A T C code, while universally in effect and enough to get us here, is an arbitrary sufficiency. In this MDPI online journal, in an Engineering Aptamers for Biomedical Applications issue, Foundation for Applied Molecular Evolution, Florida bioresearchers (search SB) consider ways to read, expand, enhance and begin to rewrite anew. From our 2020 vista, it might seem that a family genesis ecosmos wants our homo to Anthropo sapience to move from an inefficient stochastic (tinkered) past to an intentional, respectfully guided procreation. See also Aptamer Cell-Based Selection by Silvia Catuogno and Carla Esposito in this issue. A popular review of this work, along with F. Romesberg below, is Life, Rewritten by James Crow in the New Scientist (December 8, 2018).

Directed evolution was first applied to diverse libraries of DNA and RNA molecules a quarter century ago in the hope of gaining technology that would allow the creation of receptors, ligands, and catalysts on demand. Despite isolated successes, the outputs of this technology have been somewhat disappointing, perhaps because the four building blocks of standard DNA and RNA have too little functionality to have versatile binding properties, and offer too little information density to fold unambiguously. This review covers the recent literature that seeks to create an improved platform to support laboratory Darwinism, one based on an artificially expanded genetic information system (AEGIS) that adds independently replicating nucleotide “letters” to the evolving “alphabet”

Aptamers are high affinity single-stranded DNA/RNA molecules, produced by a combinatorial procedure named SELEX (Systematic Evolution of Ligands by Exponential enrichment), that are emerging as promising diagnostic and therapeutic tools.

Blain, J. Craig and Jack Szostak. Progress Toward Synthetic Cells. Annual Review of Biochemistry. Online March, 2014. As the Abstract notes, Massachusetts General Hospital, Center for Computational and Integrative Biology, researchers now predict, after years of approaches and trials, that the intentional new creation of living systems from nucleotides, proteins, microbes, and so on, is now a matter of time and endeavor. This is notable since Szostak received the 2009 Nobel Prize in Chemistry.

The complexity of even the simplest known life forms makes efforts to synthesize living cells from inanimate components seem like a daunting task. However, recent progress toward the creation of synthetic cells, ranging from simple protocells to artificial cells approaching the complexity of bacteria, suggests that the synthesis of life is now a realistic goal. Protocell research, fueled by advances in the biophysics of primitive membranes and the chemistry of nucleic acid replication, is providing new insights into the origin of cellular life. Parallel efforts to construct more complex artificial cells, incorporating translational machinery and protein enzymes, are providing information about the requirements for protein-based life. We discuss recent advances and remaining challenges in the synthesis of artificial cells, the possibility of creating new forms of life distinct from existing biology, and the promise of this research for gaining a deeper understanding of the nature of living systems. (Abstract)

Bonomo, Melia and Michael Deem. The Physicist’s Guide to One of Biotechnology’s Hottest New Topics: CRISPR-Cas. arXiv:1712.09865. Rice University biophysicists (search MD) offer a 64 page perspective about adaptive topologies, immunity, genetic expression, interference, memories, and other relevant properties, which can be given a physical basis. An example is a notice of Markov mathematics in genomic phenomena. By their lights, a Lamarckian-type evolutionary process may then become apparent.

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) constitute a multi-functional, constantly evolving immune system in bacteria and archaea cells. A heritable, molecular memory is generated of phage, plasmids, or other mobile genetic elements that attempt to attack the cell. Here we review a large body of CRISPR-Cas research to explore themes of evolution and selection, population dynamics, horizontal gene transfer, specific and cross-reactive interactions, cost and regulation, as well as non-defensive CRISPR functions that boost host cell robustness. Physical understanding of the CRISPR-Cas system will advance applications, such as efficient and specific genetic engineering, cell labeling and information storage, and combating antibiotic resistance. (Abstract)

Cable, Jennifer, et al. Synthetic Biology: At the Crossroads of Genetic Engineering and Human Therapeutics. Annals of the New York Academy of Sciences. November, 2021. A summary report on this Keystone Symposia with thirty, diverse contributors and a broad objective of gaining some scientific and ethical bearings going forward.

Synthetic biology has the potential to transform cell- and gene-based therapies for a variety of diseases. Advanced methods are now available to modify eukaryotic and prokaryotic cells so to selectively achieve palliative effects in response to one or more disease-related signals. This report summarizes the Keystone eSymposium with the above title which took place on May 3 and 4, 2021. Presenters discussed the use of synthetic biology to improve T cell, gene, and viral therapies, to engineer probiotics, and to expand upon existing modalities and functions of cell-based therapies.

Cameron, Ewen, et al. A Brief History of Synthetic Biology. Natures Reviews Microbiology. 12/5, 2014. Researchers at Howard Hughes Medical Institute, Boston provide a succinct retrospective and timeline survey so as to orient current and future endeavors and advances.

The ability to rationally engineer microorganisms has been a long-envisioned goal dating back more than a half-century. With the genomics revolution and rise of systems biology in the 1990s came the development of a rigorous engineering discipline to create, control and programme cellular behaviour. The resulting field, known as synthetic biology, has undergone dramatic growth throughout the past decade and is poised to transform biotechnology and medicine. This Timeline article charts the technological and cultural lifetime of synthetic biology, with an emphasis on key breakthroughs and future challenges. (Abstract)

Cepelewicz, Jordana. Is a Bigger Genetic Code Better? Get Ready to Find Out. Quanta. Online January 2, 2018. A science writer surveys the current burst of capabilities and projects to begin, after some 13.8 billion cosmic years, to edit, alter, redesign, and radically expand nature’s past version of four letters for 20 amino acids. The article is based on interviews with and reports by leading edge researchers such as Steven Benner, Floyd Romesberg, George Church, Stephen Freeland and Jason Chin. While “nature’s head start” of a good enough but trial and error code brought life and people to this point, a second genesis horizon opens before us which invites our respectfully informed editorial and authorial continuance.

The ability to increase the number of base pairs or amino acids changes the rules of that game entirely. Because even a binary system of bases would have been incredibly efficient, many researchers posit that primitive cellular life began with a single pair of bases, and evolved a second pair only after cellular systems became more complex and sophisticated, and a higher information density in DNA became advantageous. But why stop at four? “Would upgrading to six or eight bases be augmenting this?” Freeland asked. “You’d get even more information per length of genetic segment. It would be very interesting to see the ramifications of that, to see if it would actually make something better and more efficient. (5, sample text)

Chari, Raj and George Church. Beyond Editing to Writing Large Genomes. Nature Reviews Genetics. Online September, 2017. Harvard Medical School geneticists press on at these frontiers of church work as it becomes evident that we collaborative persons have an unlimited capacity to do this, while in turn this genetic realm seems most amenable for us to proceed.

Recent exponential advances in genome sequencing and engineering technologies have enabled an unprecedented level of interrogation into the impact of DNA variation (genotype) on cellular function (phenotype). Furthermore, these advances have also prompted realistic discussion of writing and radically re-writing complex genomes. In this Perspective, we detail the motivation for large-scale engineering, discuss the progress made from such projects in bacteria and yeast and describe how various genome-engineering technologies will contribute to this effort. Finally, we describe the features of an ideal platform and provide a roadmap to facilitate the efficient writing of large genomes. (Abstract)

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