Synthetic Biology
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Addressing Evolutionary Questions with Synthetic Biology
Addressing evolutionary questions with synthetic biology Florian Baier and Yolanda Schaerli Department of Fundamental Microbiology, University of Lausanne, Biophore Building, 1015 Lausanne, Switzerland Correspondence: [email protected]; [email protected] Abstract Synthetic biology emerged as an engineering discipline to design and construct artificial biological systems. Synthetic biological designs aim to achieve specific biological behavior, which can be exploited for biotechnological, medical and industrial purposes. In addition, mimicking natural systems using well-characterized biological parts also provides powerful experimental systems to study evolution at the molecular and systems level. A strength of synthetic biology is to go beyond nature’s toolkit, to test alternative versions and to study a particular biological system and its phenotype in isolation and in a quantitative manner. Here, we review recent work that implemented synthetic systems, ranging from simple regulatory circuits, rewired cellular networks to artificial genomes and viruses, to study fundamental evolutionary concepts. In particular, engineering, perturbing or subjecting these synthetic systems to experimental laboratory evolution provides a mechanistic understanding on important evolutionary questions, such as: Why did particular regulatory networks topologies evolve and not others? What happens if we rewire regulatory networks? Could an expanded genetic code provide an evolutionary advantage? How important is the structure of genome and number of chromosomes? Although the field of evolutionary synthetic biology is still in its teens, further advances in synthetic biology provide exciting technologies and novel systems that promise to yield fundamental insights into evolutionary principles in the near future. 1 1. Introduction Evolutionary biology traditionally studies past or present organisms to reconstruct past evolutionary events with the aim to explain and predict their evolution. -
Global Transposon Mutagenesis and a Minimal Mycoplasma Genome
R EPORTS thermore, while immunosubunit precursors- stained positive, whereas no staining of PA28Ϫ/Ϫ purchased from PharMingen (San Diego, CA). 25D1.16 containing 15S proteasome assembly inter- cells was observed. (10) and a PA28a-specific antiserum (2) were kindly 11. S. C. Jameson, F. R. Carbone, M. J. Bevan, J. Exp. Med. provided by A. Porgador and M. Rechsteiner, respective- mediates were detected in wild-type cells, 177, 1541 (1993). ly. Metabolic labeling, immunoprecipitation, immuno- under identical conditions 15S complexes 12. T. Preckel and Y. Yang, unpublished results. blotting, and sodium dodecyl sulfateÐpolyacrylamide were hardly detectable in PA28Ϫ/Ϫ cells (Fig. 13. M. Ho, Cytomegalovirus: Biology and Infection (Ple- gel electrophoresis (SDS-PAGE) were performed as de- 4B). Notably, PA28 was found to be associ- num, New York, ed. 2, 1991). scribed (3). 14. P. Borrow and M. B. A. Oldstone, in Viral Pathogenesis, 19. T. Flad et al., Cancer Res. 58, 5803 (1998). ated with the immunosubunit precursor-con- N. Nathanson, Ed. (Lippincott-Raven, Philadelphia, 20. M. W. Moore, F. R. Carbone, M. J. Bevan, Cell 54, 777 taining 15S complexes, suggesting that PA28 1997), pp. 593Ð627; M. J. Buchmeier and A. J. Zajac, (1988). is required for the incorporation of immuno- in Persistent Virus Infections, R. Ahmed and I. Chen, 21. A. Vitiello et al., Eur. J. Immunol. 27, 671 (1997). Eds. ( Wiley, New York, 1999), pp. 575Ð605. subunits into proteasomes. 22. H. Bluthmann et al., Nature 334, 156 (1988). 15. G. Niedermann et al., J. Exp. Med. 186, 209 (1997); 23. W. Jacoby, P. V. Cammarata, S. -
Intelligent Design, Abiogenesis, and Learning from History: Dennis R
Author Exchange Intelligent Design, Abiogenesis, and Learning from History: Dennis R. Venema A Reply to Meyer Dennis R. Venema Weizsäcker’s book The World View of Physics is still keeping me very busy. It has again brought home to me quite clearly how wrong it is to use God as a stop-gap for the incompleteness of our knowledge. If in fact the frontiers of knowledge are being pushed back (and that is bound to be the case), then God is being pushed back with them, and is therefore continually in retreat. We are to find God in what we know, not in what we don’t know; God wants us to realize his presence, not in unsolved problems but in those that are solved. Dietrich Bonhoeffer1 am thankful for this opportunity to nature, is the result of intelligence. More- reply to Stephen Meyer’s criticisms over, this assertion is proffered as the I 2 of my review of his book Signature logical basis for inferring design for the in the Cell (hereafter Signature). Meyer’s origin of biological information: if infor- critiques of my review fall into two gen- mation only ever arises from intelli- eral categories. First, he claims I mistook gence, then the mere presence of Signature for an argument against bio- information demonstrates design. A few logical evolution, rendering several of examples from Signature make the point my arguments superfluous. Secondly, easily: Meyer asserts that I have failed to refute … historical scientists can show that his thesis by not providing a “causally a presently acting cause must have adequate alternative explanation” for the been present in the past because the origin of life in that the few relevant cri- proposed candidate is the only known tiques I do provide are “deeply flawed.” cause of the effect in question. -
The Transcriptional Landscape of a Rewritten Bacterial Genome Reveals Control Elements and Genome Design Principles ✉ ✉ Mariëlle J
ARTICLE https://doi.org/10.1038/s41467-021-23362-y OPEN The transcriptional landscape of a rewritten bacterial genome reveals control elements and genome design principles ✉ ✉ Mariëlle J. F. M. van Kooten 1 , Clio A. Scheidegger1, Matthias Christen1 & Beat Christen 1 Sequence rewriting enables low-cost genome synthesis and the design of biological systems with orthogonal genetic codes. The error-free, robust rewriting of nucleotide sequences can 1234567890():,; be achieved with a complete annotation of gene regulatory elements. Here, we compare transcription in Caulobacter crescentus to transcription from plasmid-borne segments of the synthesized genome of C. ethensis 2.0. This rewritten derivative contains an extensive amount of supposedly neutral mutations, including 123’562 synonymous codon changes. The tran- scriptional landscape refines 60 promoter annotations, exposes 18 termination elements and links extensive transcription throughout the synthesized genome to the unintentional intro- duction of sigma factor binding motifs. We reveal translational regulation for 20 CDS and uncover an essential translational regulatory element for the expression of ribosomal protein RplS. The annotation of gene regulatory elements allowed us to formulate design principles that improve design schemes for synthesized DNA, en route to a bright future of iteration- free programming of biological systems. 1 Institute of Molecular Systems Biology, Department of Biology, Eidgenössische Technische Hochschule Zürich, Zürich, Switzerland. ✉ email: [email protected]; [email protected] NATURE COMMUNICATIONS | (2021) 12:3053 | https://doi.org/10.1038/s41467-021-23362-y | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-021-23362-y e can program biological systems with DNA that is In previous work, we synthesized and assembled the rewritten Wbased on native nucleotide sequences. -
The Hidden Kingdom
INTRODUCTION Fungi—The Hidden Kingdom OBJECTIVE • To provide students with basic knowledge about fungi Activity 0.1 BACKGROUND INFORMATION The following text provides an introduction to the fungi. It is written with the intention of sparking curiosity about this GRADES fascinating biological kingdom. 4-6 with a K-3 adaptation TEACHER INSTRUCTIONS TYPE OF ACTIVITY 1. With your class, brainstorm everything you know about fungi. Teacher read/comprehension 2. For younger students, hand out the question sheet before you begin the teacher read and have them follow along and MATERIALS answer the questions as you read. • copies of page 11 3. For older students, inform them that they will be given a • pencils brainteaser quiz (that is not for evaluation) after you finish reading the text. VOCABULARY 4. The class can work on the questions with partners or in groups bioremediation and then go over the answers as a class. Discuss any chitin particularly interesting facts and encourage further fungi independent research. habitat hyphae K-3 ADAPTATION kingdom 1. To introduce younger students to fungi, you can make a KWL lichens chart either as a class or individually. A KWL chart is divided moulds into three parts. The first tells what a student KNOWS (K) mushrooms about a subject before it is studied in class. The second part mycelium tells what the student WANTS (W) to know about that subject. mycorrhizas The third part tells what the child LEARNED (L) after studying nematodes that subject. parasitic fungi 2. Share some of the fascinating fungal facts presented in the photosynthesis “Fungi—The Hidden Kingdom” text with your students. -
Framing Major Prebiotic Transitions As Stages of Protocell Development: Three Challenges for Origins-Of-Life Research
Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research Ben Shirt-Ediss1, Sara Murillo-Sánchez2,3 and Kepa Ruiz-Mirazo*2,3 Commentary Open Access Address: Beilstein J. Org. Chem. 2017, 13, 1388–1395. 1Interdisciplinary Computing and Complex BioSystems Group, doi:10.3762/bjoc.13.135 University of Newcastle, UK, 2Dept. Logic and Philosophy of Science, University of the Basque Country, Spain and 3Biofisika Institute Received: 16 February 2017 (CSIC, UPV-EHU), Spain Accepted: 27 June 2017 Published: 13 July 2017 Email: Kepa Ruiz-Mirazo* - [email protected] This article is part of the Thematic Series "From prebiotic chemistry to molecular evolution". * Corresponding author Guest Editor: L. Cronin Keywords: functional integration; origins of life; prebiotic evolution; protocells © 2017 Shirt-Ediss et al.; licensee Beilstein-Institut. License and terms: see end of document. Abstract Conceiving the process of biogenesis as the evolutionary development of highly dynamic and integrated protocell populations provides the most appropriate framework to address the difficult problem of how prebiotic chemistry bridged the gap to full-fledged living organisms on the early Earth. In this contribution we briefly discuss the implications of taking dynamic, functionally inte- grated protocell systems (rather than complex reaction networks in bulk solution, sets of artificially evolvable replicating molecules, or even these same replicating molecules encapsulated in passive compartments) -
Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation
G C A T T A C G G C A T genes Review Alternative Biochemistries for Alien Life: Basic Concepts and Requirements for the Design of a Robust Biocontainment System in Genetic Isolation Christian Diwo 1 and Nediljko Budisa 1,2,* 1 Institut für Chemie, Technische Universität Berlin Müller-Breslau-Straße 10, 10623 Berlin, Germany; [email protected] 2 Department of Chemistry, University of Manitoba, 144 Dysart Rd, 360 Parker Building, Winnipeg, MB R3T 2N2, Canada * Correspondence: [email protected] or [email protected]; Tel.: +49-30-314-28821 or +1-204-474-9178 Received: 27 November 2018; Accepted: 21 December 2018; Published: 28 December 2018 Abstract: The universal genetic code, which is the foundation of cellular organization for almost all organisms, has fostered the exchange of genetic information from very different paths of evolution. The result of this communication network of potentially beneficial traits can be observed as modern biodiversity. Today, the genetic modification techniques of synthetic biology allow for the design of specialized organisms and their employment as tools, creating an artificial biodiversity based on the same universal genetic code. As there is no natural barrier towards the proliferation of genetic information which confers an advantage for a certain species, the naturally evolved genetic pool could be irreversibly altered if modified genetic information is exchanged. We argue that an alien genetic code which is incompatible with nature is likely to assure the inhibition of all mechanisms of genetic information transfer in an open environment. The two conceivable routes to synthetic life are either de novo cellular design or the successive alienation of a complex biological organism through laboratory evolution. -
The Mysterious Orphans of Mycoplasmataceae
The mysterious orphans of Mycoplasmataceae Tatiana V. Tatarinova1,2*, Inna Lysnyansky3, Yuri V. Nikolsky4,5,6, and Alexander Bolshoy7* 1 Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, 90027, California, USA 2 Spatial Science Institute, University of Southern California, Los Angeles, 90089, California, USA 3 Mycoplasma Unit, Division of Avian and Aquatic Diseases, Kimron Veterinary Institute, POB 12, Beit Dagan, 50250, Israel 4 School of Systems Biology, George Mason University, 10900 University Blvd, MSN 5B3, Manassas, VA 20110, USA 5 Biomedical Cluster, Skolkovo Foundation, 4 Lugovaya str., Skolkovo Innovation Centre, Mozhajskij region, Moscow, 143026, Russian Federation 6 Vavilov Institute of General Genetics, Moscow, Russian Federation 7 Department of Evolutionary and Environmental Biology and Institute of Evolution, University of Haifa, Israel 1,2 [email protected] 3 [email protected] 4-6 [email protected] 7 [email protected] 1 Abstract Background: The length of a protein sequence is largely determined by its function, i.e. each functional group is associated with an optimal size. However, comparative genomics revealed that proteins’ length may be affected by additional factors. In 2002 it was shown that in bacterium Escherichia coli and the archaeon Archaeoglobus fulgidus, protein sequences with no homologs are, on average, shorter than those with homologs [1]. Most experts now agree that the length distributions are distinctly different between protein sequences with and without homologs in bacterial and archaeal genomes. In this study, we examine this postulate by a comprehensive analysis of all annotated prokaryotic genomes and focusing on certain exceptions. -
Efficient and Sequence-Independent Replication of DNA Containing A
Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet Denis A. Malysheva, Kirandeep Dhamia, Henry T. Quacha, Thomas Lavergnea, Phillip Ordoukhanianb, Ali Torkamanic, and Floyd E. Romesberga,1 aDepartment of Chemistry, bCenter for Protein and Nucleic Acid Research, and cThe Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA 92037 Edited* by Jack W. Szostak, The Howard Hughes Medical Institute and Massachusetts General Hospital, Boston, MA, and approved June 6, 2012 (received for review March 27, 2012) The natural four-letter genetic alphabet, comprised of just two were hindered by low-fidelity replication and chemical instability base pairs (dA-dT and dG-dC), is conserved throughout all life, and (23), but modifications have been found more recently that its expansion by the development of a third, unnatural base pair overcome these limitations, and DNA containing such unnatural has emerged as a central goal of chemical and synthetic biology. pairs has been amplified by PCR (24). The amplification of DNA We recently developed a class of candidate unnatural base pairs, containing multiple, contiguous unnatural base pairs has also exemplified by the pair formed between d5SICS and dNaM. Here, been shown (10), but the more general effects of sequence context we examine the PCR amplification of DNA containing one or more have yet to be reported. The second strategy, originally pursued d5SICS-dNaM pairs in a wide variety of sequence contexts. Under by our group (25), and in part inspired by the observation in the standard conditions, we show that this DNA may be amplified work by Kool and coworkers (26) that H-bonds are not absolutely with high efficiency and greater than 99.9% fidelity. -
Horizontal Gene Flow Into Geobacillus Is Constrained by the Chromosomal Organization of Growth and Sporulation
bioRxiv preprint doi: https://doi.org/10.1101/381442; this version posted August 2, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Horizontal gene flow into Geobacillus is constrained by the chromosomal organization of growth and sporulation Alexander Esin1,2, Tom Ellis3,4, Tobias Warnecke1,2* 1Molecular Systems Group, Medical Research Council London Institute of Medical Sciences, London, United Kingdom 2Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom 3Imperial College Centre for Synthetic Biology, Imperial College London, London, United Kingdom 4Department of Bioengineering, Imperial College London, London, United Kingdom *corresponding author ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/381442; this version posted August 2, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Horizontal gene transfer (HGT) in bacteria occurs in the context of adaptive genome architecture. As a consequence, some chromosomal neighbourhoods are likely more permissive to HGT than others. Here, we investigate the chromosomal topology of horizontal gene flow into a clade of Bacillaceae that includes Geobacillus spp. Reconstructing HGT patterns using a phylogenetic approach coupled to model-based reconciliation, we discover three large contiguous chromosomal zones of HGT enrichment. -
Section 4. Guidance Document on Horizontal Gene Transfer Between Bacteria
306 - PART 2. DOCUMENTS ON MICRO-ORGANISMS Section 4. Guidance document on horizontal gene transfer between bacteria 1. Introduction Horizontal gene transfer (HGT) 1 refers to the stable transfer of genetic material from one organism to another without reproduction. The significance of horizontal gene transfer was first recognised when evidence was found for ‘infectious heredity’ of multiple antibiotic resistance to pathogens (Watanabe, 1963). The assumed importance of HGT has changed several times (Doolittle et al., 2003) but there is general agreement now that HGT is a major, if not the dominant, force in bacterial evolution. Massive gene exchanges in completely sequenced genomes were discovered by deviant composition, anomalous phylogenetic distribution, great similarity of genes from distantly related species, and incongruent phylogenetic trees (Ochman et al., 2000; Koonin et al., 2001; Jain et al., 2002; Doolittle et al., 2003; Kurland et al., 2003; Philippe and Douady, 2003). There is also much evidence now for HGT by mobile genetic elements (MGEs) being an ongoing process that plays a primary role in the ecological adaptation of prokaryotes. Well documented is the example of the dissemination of antibiotic resistance genes by HGT that allowed bacterial populations to rapidly adapt to a strong selective pressure by agronomically and medically used antibiotics (Tschäpe, 1994; Witte, 1998; Mazel and Davies, 1999). MGEs shape bacterial genomes, promote intra-species variability and distribute genes between distantly related bacterial genera. Horizontal gene transfer (HGT) between bacteria is driven by three major processes: transformation (the uptake of free DNA), transduction (gene transfer mediated by bacteriophages) and conjugation (gene transfer by means of plasmids or conjugative and integrated elements). -
Flourishing and Discordance: on Two Modes of Human Science Engagement with Synthetic Biology
Flourishing and Discordance: On Two Modes of Human Science Engagement with Synthetic Biology by Anthony Stavrianakis A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Anthropology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Paul Rabinow, Chair Professor Xin Liu Professor Charis Thompson Fall 2012 Abstract Flourishing and Discordance: On Two Modes of Human Science Engagement with Synthetic Biology by Anthony Stavrianakis Doctor of Philosophy in Anthropology University of California, Berkeley Professor Paul Rabinow, Chair This dissertation takes up the theme of collaboration between the human sciences and natural sciences and asks how technical, veridictional and ethical vectors in such co-labor can be inquired into today. I specify the problem of collaboration, between forms of knowledge, as a contemporary one. This contemporary problem links the recent past of the institutional relations between the human and natural sciences to a present experience of anthropological engagement with a novel field of bioengineering practice, called synthetic biology. I compare two modes of engagement, in which I participated during 2006–2011. One project, called Human Practices, based within the Synthetic Biology Engineering Research Center (SynBERC), instantiated an anthropological mode of inquiry, explicitly oriented to naming ethical problems for collaboration. This project, conducted in collaboration with Paul Rabinow and Gaymon Bennett, took as a challenge the invention of an appropriate practice to indeterminate ethical problems. Flourishing, a translation of the ancient Greek term eudaemonia, was a central term in orienting the Human Practices project. This term was used to posit ethical questions outside of the instrumental rationality of the sciences, and on which the Human Practices project would seek to work.