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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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Genesis Vision
Learning Planet
Organic Universe
Earth Life Emerge
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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

Cheng, Feng, et al. Directed Evolution 2.0: Improving and Deciphering Enzyme Properties. Chemical Communications. 51/9760, 2015. In an issue edited by Nicholas Turner and Frances Arnold on this title topic, RWTH Aachen University researchers Chen, Leilei Zhu, and Ulrich Schwaneberg review the fertile field of a mindful “engineering” of protein forms and metabolic dynamics for organism, community and environment, broadly conceived. Again we cite as an entry among many, see also, e.g., Constitutional Self-selection from Dynamic Combinatorial Libraries in Aqueous Solution through Supramolecular Interactions by Jordi Sola in this journal (50/4564, 2014).

Directed evolution has matured to a routinely applied algorithm to tailor enzyme properties to meet the demands in various applications. In order to free directed enzyme evolution from methodological restraints and to efficiently explore its potential, many different strategies have been used in directed evolution campaigns. Analysis of directed evolution campaigns reveals that traditional approaches, in which several iterative rounds of diversity generation and screening are performed, are gradually replaced by strategies which require less time, less screening efforts, and generate a molecular understanding of the targeted properties. In this review, conceptual advances in knowledge generating directed evolution strategies are summarized, compared to each other and to traditional directed evolution strategies. Finally, a ‘KnowVolution’ (knowledge gaining directed evolution) termed strategy is proposed. (Cheng Abstract)

We describe the predominant formation of a specific constitution arising from the combination of building blocks with different topologies through disulphide chemistry in a Dynamic Combinatorial Library (DCL). The supramolecular interactions established by a zwitterionic cysteine moiety are responsible for the self-selection of one product from all the virtual members of a large library. (Sola Abstract)

Chin, Jason. Expanding and Reprogramming the Genetic Code. Nature. 550/53, 2017. The MRC Laboratory of Molecular Biology, Cambridge University geneticist reports upon his Centre for Chemical and Synthetic Biology project of systematic genetic code reprogramming, which is here explained in graphic technical expertise. For reference see his earlier Expanding and Reprogramming the Genetic Code of Cells and Animals in the Annual Review of Biochemistry (83/379, 2017), both Abstracts below.

Nature uses a limited, conservative set of amino acids to synthesize proteins. The ability to genetically encode an expanded set of building blocks with new chemical and physical properties is transforming the study, manipulation and evolution of proteins, and is enabling diverse applications, including approaches to probe, image and control protein function, and to precisely engineer therapeutics. Underpinning this transformation are strategies to engineer and rewire translation. Emerging strategies aim to reprogram the genetic code so that noncanonical biopolymers can be synthesized and evolved, and to test the limits of our ability to engineer the translational machinery and systematically recode genomes. (2017 Abstract)

Genetic code expansion and reprogramming enable the site-specific incorporation of diverse designer amino acids into proteins produced in cells and animals. Recent advances are enhancing the efficiency of unnatural amino acid incorporation by creating and evolving orthogonal ribosomes and manipulating the genome. Increasing the number of distinct amino acids that can be site-specifically encoded has been facilitated by the evolution of orthogonal quadruplet decoding ribosomes and the discovery of mutually orthogonal synthetase/tRNA pairs. Rapid progress in moving genetic code expansion from bacteria to eukaryotic cells and animals (C. elegans and D. melanogaster) and the incorporation of useful unnatural amino acids has been aided by the development and application of the pyrrolysyl–transfer RNA (tRNA) synthetase/tRNA pair for unnatural amino acid incorporation. (2014 Abstract)

Church, George and Ed Regis. Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves. New York: Basic Books, 2012. A renowned Harvard Medical School geneticist and a science writer achieve an informed, universe to us, manifesto going forward as regnant humans may now begin a new creation, a second intentional genesis. A Prologue is “From Bioplastics to H. Sapiens 2.0,” with degrees of high tech computerese. Ch. 2 is “-3,500 Myr Archean: Reading the Most Ancient Texts and the Future of Living Software.” Similar scintillations follow evolution’s course of “natural genome engineering” all the way to an Epigenetic Epilogue: “The End of the Beginning, Transhumanism and the Panspermia Era.” An innovative concept of emergent life as “replicated complexity” or “replexity” is introduced, as pervasive genetic programs run and iterate. Dr. Church believes these advances have the potential to fully heal our maladies and diseases of soma, psyche, and indeed the biosphere, while quite aware of necessities for strident controls.

A brief review does not do justice. For starters, one may note that almost everyone cited is a man. This auspicious past, present, and future scenario is traversed without wonderment as to whatever may be going on, what could it all be and mean. On the face of it, a 21st century recognition of a greater nature deeply textual in its generative essence is recorded, albeit algorithmic in kind, which we are summoned to decipher (sequence), translate and read. The final bold quote is a rare allusion to a universal genome, which this website tries to document and convey. George Church says he is a speaker at Ray Kurzweil’s Singularity University (search). Is evolution mechanically “random” or is something like a (maternal) developmental gestation going on? Are collectively intelligent persons, as if genes and neurons, the phenomenal way a genesis uniVerse tries to consciously read, and carry forth, its own genetic code?

Just as computers were universal machines in the sense that given the appropriate programming they could simulate the activities of any other machine, so biological organisms approached the condition of being universal constructors in the sense that with appropriate changes to their genetic programming, they could be made to produce practically any imaginable artifact. A living organism, after all, was a ready-made, prefabricated production system that, like a computer, was governed by a program, its genome. Synthetic biology and synthetic genomics, the large-scale remaking of a genome, were attempts to capitalize on the facts that by making small changes in their genetic software a bioengineer can effect changes in their output. (4)

The original ancient text is written in the genomic DNA of every being alive today. That text is as old as life itself, and over 1030copies of it are distributed around the earth, from 5 kilometers deep within the earth’s crust to the edge of our atmosphere, and in every drop of the ocean. For such a significant text, its translation into modern languages began only recently, in the 1970s. Other naturalistic, geological, and astronomical resources can also be considered ancient texts. We surmise that the ancients text written by humans, as well as the texts of natural data, are all transmitting profound truths that are not intrinsically contradictory. We try to align and weave these various threads to help us understand the past and the future. (38)

My gut feeling is that, despite limitations of space and time, we humans can suddenly start to evolve thousands of times faster than the impressive Cambrian era, and that we can direct this diversity toward our material needs instead of letting it occur randomly. (73) As a general goal I propose that, as a minimum, we ought to avoid the loss of all intelligent life in the universe. (244) The genome should become not the genome of one lonely being or one planet. It should become the genome of the Universe. (244)

Cobb, Ryan, et al. Directed Evolution: An Evolving and Enabling Synthetic Biology Tool. Current Opinion in Chemical Biology. 16/285, 2012. University of Illinois biomolecular engineers propose to join techniques which deal with parts and circuits into inclusive complex pathways and systems. By an emphasis on such interactions, a new mode of assisted evolutionary processes can better begin this second genesis phase of informed human ingenuity. In the same issue an editorial A Different Life? stresses the value of this research for its palliative benefit to beings and societies.

Synthetic biology, with its goal of designing biological entities for wide-ranging purposes, remains a field of intensive research interest. However, the vast complexity of biological systems has heretofore rendered rational design prohibitively difficult. As a result, directed evolution remains a valuable tool for synthetic biology, enabling the identification of desired functionalities from large libraries of variants. This review highlights the most recent advances in the use of directed evolution in synthetic biology, focusing on new techniques and applications at the pathway and genome scale. (Abstract)

Cussat-Blanc, Sylvain, et al. Artificial Gene Regulatory Networks. Artificial Life. 24/4, 2018. Computational biologists S C-B, University of Toulouse, Kyle Harrington, University of Idaho, and Walter Banzhaf, Michigan State University (search) review past theories, present appreciations and future utilities of this genomic feature which dynamically links diverse nucleotides into equally real, functional systems. Its wide range covers Gene Regulation in Nature, GRNs in Cellular Physiology, Development, Evolution, and Epigenetics, GRN Internal Dynamics, and onto Artificial GRNs in Embryogenesis, braced by some 150 references. In regard, a broad train is taken from earlier biomolecular components to their 21st century integrative connections. In the later 2010s going forward, new ventures can be scoped out with palliative and procreative horizons.

In nature, gene regulatory networks are a key mediator between the information stored in the DNA of living organisms (their genotype) and the structural and behavioral expression this finds in their bodies, surviving in the world (their phenotype). They integrate environmental signals, steer development, buffer stochasticity, and allow evolution to proceed. In engineering, modeling and implementations of artificial gene regulatory networks have been an expanding field of research and development over the past few decades. This review discusses the concept of gene regulation, describes the current state of the art in gene regulatory networks, including modeling and simulation, and reviews their use in artificial evolutionary settings. We provide evidence for the benefits of this concept in natural and the engineering domains. (Abstract)

In summary, gene regulation has emerged as a key player in translating the information provided by an organism's inherited DNA into the structure (via growth and development) and behavior of that organism. Time scales range from seconds (in the case of the regulation of metabolism in neurons to thousands of years (in the case of evolutionary processes). Gene regulatory networks have been compared to the compilers of computer languages that translate code into behavior of the underlying machine. However, there is much more to the computational modeling of gene regulation, and this brings us to our next topic. (301)

Possibilities opened by gene regulatory networks are numerous. Whereas biologists have made significant progress in understanding the inner mechanisms of gene regulation in living systems, much remains to be discovered and understood. These mechanisms produce extremely complex behaviors in living organisms, from embryogenesis to the regulation of everyday life. Computer science and more specifically artificial intelligence will benefit from these discoveries and, with gene regulatory networks, could produce more intelligent behaviors for artificial agents in the near future. (321)

Dalchau, Neil, et al. Towards the Rational Design of Synthetic Cells with Prescribed Population Dynamics. Journal of the Royal Society Interface. Online June, 2012. Microsoft Research Cambridge, University of Grenoble, and University of Cambridge scientists report upon efforts to apply life’s system dynamics to intentionally achieve socially valuable cellular creations. Our philosophic interest is to imagine such capabilities as commencing a second natural genesis whence the human phenomenon can employ and carry forth these innate principles.

The rational design of synthetic cell populations with prescribed behaviours is a long-standing goal of synthetic biology, with the potential to greatly accelerate the development of biotechnological applications in areas ranging from medical research to energy production. Achieving this goal requires well-characterized components, modular implementation strategies, simulation across temporal and spatial scales and automatic compilation of high-level designs to low-level genetic parts that function reliably inside cells. Here, we address these challenges by developing a prototype framework for designing synthetic cells with prescribed population dynamics. We extend the genetic engineering of cells (GEC) language, originally developed for programming intracellular dynamics, with cell population factors such as cell growth, division and dormancy, together with spatio-temporal simulation methods. An analysis of our design reveals that environmental factors such as density-dependent dormancy and reduced extracellular space destabilize the population dynamics and increase the range of genetic variants for which complex spatio-temporal behaviours are possible. We then use our analysis of population dynamics to inform the selection of genetic parts, which could be used to obtain the desired spatio-temporal behaviours. (Abstract)

Davies, Jamie. Real-World Synthetic Biology. Life. 9/1, 2019. A paper by the University of Edinburgh morphologist (search) for Ricard Sole’s Synthetic Biology from Living Computers to Terraformation issue, see second quote. Similar to Manuel Porcar’s entry herein, at this epic turning point it is vital to get clear on and use consistent life-like metaphors and terms. Thus specific engineering and industrial control methods are not seen as appropriate. Davies proceeds to graphically propose self-organizing organic procedures by way of complex adaptive systems.

Authors often assert that a key feature of 21st-century synthetic biology is its use of an engineering design approach using predictive models, modular architecture, construction using well-characterized parts, and rigorous testing using standard metrics. This article examines whether this is, or even should be, the case. A brief survey of synthetic biology projects that have reached, or are near to, commercial application show very few of these attributes. Instead, they featured much trial and error, and the use of specialized, custom components and assays. I conclude that the engineering approach should not be used to define or constrain synthetic biological endeavour, and that in fact conventional engineering has more to gain by expanding and embracing more biological ways of working. (Davies Abstract excerpts)

Over the last two decades, synthetic biology has emerged as a novel field with major impact on both basic science and biomedical research. By moving beyond the classical approaches of genetic engineering, synthetic circuits implemented within living cells allow to redesign nature from the molecular and cellular levels to multicellular scales. Synthetic microorganisms have been built to explore cooperation and conflict in microbial interactions as well as the rise of multicellularity. Complex computational tasks have also been created de novo and used to expand the cognitive potential of cellular assemblies. In parallel with all these already promising results, synthetic biology is being considered as a potential path to artificially modify microbiomes and even terraform Mars biosphere. (R. Sole proposal)

De la Torre, Daniel and Jason Chin. Reprogramming the Genetic Code. Nature Reviews Genetics. 22/3, 2021. Medical Research Council Laboratory of Molecular Biology, Cambridge, UK geneticists (search JC) describe some latest wa that this 2010s project to begin to add letters and parsing phrases to life’s evolutionary codification.

The encoded biosynthesis of proteins provides the ultimate paradigm for high-fidelity synthesis of long polymers of defined sequence and composition, but it is limited to polymerizing the canonical amino acids. Recent advances have built on genetic code expansion to enable the encoded incorporation of several distinct non-canonical amino acids. Developments include strategies to read quadruplet codons, use non-natural DNA base pairs, synthesize completely recoded genomes and create orthogonal translational components with reprogrammed specificities. These advances may enable the genetically encoded synthesis of non-canonical biopolymers and transform the discovery and evolution of new materials and therapeutic uses. (Abstract)

Dehne, Henry, et al. Transient Self-Organization of DNA Coated Colloids Directed by Enzymatic Reactions. Nature Scientific Reports. 9/7350, 2019. Technical University of Munich chemists including group leader Andreas Bausch (second quote and website), research ways by which complex system methods can help study nucleotide molecules so to serve life’s new intentional, informed procreation.

Dynamic self-organisation far from equilibrium is a key concept towards building autonomously acting materials. Here, we report the coupling of an antagonistic enzymatic reaction of RNA polymerisation and degradation to the aggregation of micron sized DNA coated colloids into fractal structures. A transient colloidal aggregation process is controlled by competing reactions of RNA synthesis of linker strands by a RNA polymerase and their degradation by a ribonuclease. By limiting the energy supply (NTP) of the enzymatic reactions, colloidal clusters form and subsequently disintegrate without the need of external stimuli. (Abstract)

Understanding complex biomaterials on a fundamental physical basis is an integral challenge of future biophysical research. This challenge can be addressed by the concerted application of new experimental tools of soft condensed matter physics to living cells and bio-mimetic model systems. In our group we concentrate on the one hand on developing new physical tools to address the underlying complexity and mechanisms and on the other hand on developing new biomaterials for applications ranging from biomedicine to functional food. (TUM Cellular Biophysics)

Dekker, Job, et al. The 4D Nucleome Project. Nature. 549/219, 2017. Thirteen authors representing the 4D Nucleome Network of major universities and institutes across the USA describe and specify this latest endeavor, as all the biomolecular parts and pieces become known, of visualizing whole genomic phenomena. The endeavor involves Mapping, Model Building, and Positional Validation, along with software such as chromosome conformation, replicated DNA sequencing, imaging techniques, and so on.

The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the goal of gaining deeper mechanistic insights into how the nucleus is organized and functions. The project will develop and benchmark experimental and computational approaches for measuring genome conformation and nuclear organization, and investigate how these contribute to gene regulation and other genome functions. Validated experimental technologies will be combined with biophysical approaches to generate quantitative models of spatial genome organization in different biological states, both in cell populations and in single cells. (Abstract)

After determining the complete DNA sequence of the human genome and subsequent mapping of most genes and potential regulatory elements, we are now in a position that can be considered the third phase of the human genome project. In this phase, which builds upon and extends other epigenome mapping efforts mentioned above, the spatial organization of the genome is elucidated and its functional implications revealed. This requires a wide array of technologies from the fields of imaging, genomics, genetic engineering, biophysics, computational biology and mathematical modelling. The 4DN Network, as presented here, provides a mechanism to address this uniquely interdisciplinary challenge. (225)

The Common Fund’s 4D Nucleome program aims to understand the principles underlying nuclear organization in space and time, the role nuclear organization plays in gene expression and cellular function, and how changes in nuclear organization affect normal development as well as various diseases. This program will develop technologies, resources and data to enable the study of the 4D Nucleome, including novel tools to explore the dynamic nuclear architecture and its role in gene expression programs, models to examine the relationship between nuclear organization and function in both normal development and disease, and reference maps of nuclear architecture in a variety of cells and tissues.

Design, Jai and Chaitanya Gokhale.. Synthetic Mutualism and the Intervention Dilemma. Life. 9/1, 2019. Okinawa Institute of Science and Technology, Genomics and Regulatory Systems Unit, and MPI Evolutionary Biology, Theoretical Models of Eco-Evolutionary Dynamics Group researchers extend this nascent endeavor to both gain a better understanding of how life has naturally evolved, developed and emerged, and how our human sapience might begin a intentional procreation by respectful, informed continuance. A working phrase herein is a Synthetic Symbiosis, which could also inspire better human communities.

Ecosystems are complex networks of interacting individuals co-evolving with their environment. As such, changes to an interaction can influence the whole ecosystem. However, to predict the outcome of these changes, considerable understanding of processes driving the system is required. Synthetic biology provides tools to aid this understanding, which then may allow us to change specific interactions. Of particular interest is the ecological importance of mutualism, a subset of cooperative interactions. Mutualism occurs when individuals of different species provide a reciprocal fitness benefit. We review available experimental techniques from the stability of microbial communities in extreme environments to the collapse of ecosystems due to high levels of human intervention. We evaluate the promise of synthetic biology by way of ethics and laws regarding biological alterations, whether on Earth or beyond. (Abstract excerpt)

Dien, Vivian, et al. Progress Toward a Semi-Synthetic Organism with an Unrestricted Expanded Genetic Alphabet. Journal of the American Chemical Society. 140/47, 2018. A six person team from Floyd Romesberg’s laboratory at the Scripps Research Institute, La Jolla, CA describe a highly technical exercise by which to begin modifications and enhancements of life’s original four letter genomic code. The work was noted in the popular press as Life, Rewritten by James Crow (New Scientist, Dec. 8, 2018), see also the Biondi and Benner entry above.

We have developed a family of unnatural base pairs (UBPs), exemplified by the pair formed between dNaM and dTPT3, for which pairing is mediated not by complementary hydrogen bonding but by hydrophobic and packing forces. These UBPs enabled the creation of the first semisynthetic organisms (SSOs) that store increased genetic information and use it to produce proteins containing noncanonical amino acids. The results demonstrate the importance of evaluating synthetic biology “parts” in their in vivo context and the ability of hydrophobic and packing interactions to replace the complementary hydrogen bonding that underlies the replication of natural base pairs. The identification of dMTMO-dTPT3 and especially dPTMO-dTPT3 represents significant progress toward the development of SSOs able to store and retrieve increased information. (Abstract excerpt)

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