Life | Editor’s choice Articles

17 pages, 4264 KiB

Open AccessEditor’s ChoiceReview

Enigmatic Histamine Receptor H₄ for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases

by Pakhuri Mehta, Przemysław Miszta, Przemysław Rzodkiewicz, Olga Michalak, Piotr Krzeczyński and Sławomir Filipek

Life 2020, 10(4), 50; https://doi.org/10.3390/life10040050 - 24 Apr 2020

Cited by 29 | Viewed by 13529

Abstract

The histamine H₄ receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H₄R ligands are being studied for the treatment of several inflammatory, [...] Read more.

The histamine H₄ receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H₄R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H₄R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H₄R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood. Full article

(This article belongs to the Section Pharmaceutical Science)

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27 pages, 38043 KiB

Open AccessEditor’s ChoiceArticle

Synthetic Biology for Terraformation Lessons from Mars, Earth, and the Microbiome

by Nuria Conde-Pueyo, Blai Vidiella, Josep Sardanyés, Miguel Berdugo, Fernando T. Maestre, Victor de Lorenzo and Ricard Solé

Life 2020, 10(2), 14; https://doi.org/10.3390/life10020014 - 9 Feb 2020

Cited by 33 | Viewed by 15712

Abstract

What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering [...] Read more.

What is the potential for synthetic biology as a way of engineering, on a large scale, complex ecosystems? Can it be used to change endangered ecological communities and rescue them to prevent their collapse? What are the best strategies for such ecological engineering paths to succeed? Is it possible to create stable, diverse synthetic ecosystems capable of persisting in closed environments? Can synthetic communities be created to thrive on planets different from ours? These and other questions pervade major future developments within synthetic biology. The goal of engineering ecosystems is plagued with all kinds of technological, scientific and ethic problems. In this paper, we consider the requirements for terraformation, i.e., for changing a given environment to make it hospitable to some given class of life forms. Although the standard use of this term involved strategies for planetary terraformation, it has been recently suggested that this approach could be applied to a very different context: ecological communities within our own planet. As discussed here, this includes multiple scales, from the gut microbiome to the entire biosphere. Full article

(This article belongs to the Section Synthetic Biology and Systems Biology)

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15 pages, 2706 KiB

Open AccessEditor’s ChoiceArticle

A Strategy for Combinatorial Cavity Design in De Novo Proteins

by Christina Karas and Michael Hecht

Life 2020, 10(2), 9; https://doi.org/10.3390/life10020009 - 23 Jan 2020

Cited by 12 | Viewed by 4947

Abstract

Protein sequence space is vast; nature uses only an infinitesimal fraction of possible sequences to sustain life. Are there solutions to biological problems other than those provided by nature? Can we create artificial proteins that sustain life? To investigate these questions, we have [...] Read more.

Protein sequence space is vast; nature uses only an infinitesimal fraction of possible sequences to sustain life. Are there solutions to biological problems other than those provided by nature? Can we create artificial proteins that sustain life? To investigate these questions, we have created combinatorial collections, or libraries, of novel sequences with no homology to those found in living organisms. Previously designed libraries contained numerous functional proteins. However, they often formed dynamic, rather than well-ordered structures, which complicated structural and mechanistic characterization. To address this challenge, we describe the development of new libraries based on the de novo protein S-824, a 4-helix bundle with a very stable 3-dimensional structure. Distinct from previous libraries, we targeted variability to a specific region of the protein, seeking to create potential functional sites. By characterizing variant proteins from this library, we demonstrate that the S-824 scaffold tolerates diverse amino acid substitutions in a putative cavity, including buried polar residues suitable for catalysis. We designed and created a DNA library encoding 1.7 × 10⁶ unique protein sequences. This new library of stable de novo α-helical proteins is well suited for screens and selections for a range of functional activities in vitro and in vivo. Full article

(This article belongs to the Special Issue Design and Validation of Tools for Microbial Synthetic Biology Applications)

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41 pages, 4490 KiB

Open AccessEditor’s ChoiceConcept Paper

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

by Didier Auboeuf

Life 2020, 10(2), 7; https://doi.org/10.3390/life10020007 - 21 Jan 2020

Cited by 17 | Viewed by 8364

Abstract

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of [...] Read more.

The current framework of evolutionary theory postulates that evolution relies on random mutations generating a diversity of phenotypes on which natural selection acts. This framework was established using a top-down approach as it originated from Darwinism, which is based on observations made of complex multicellular organisms and, then, modified to fit a DNA-centric view. In this article, it is argued that based on a bottom-up approach starting from the physicochemical properties of nucleic and amino acid polymers, we should reject the facts that (i) natural selection plays a dominant role in evolution and (ii) the probability of mutations is independent of the generated phenotype. It is shown that the adaptation of a phenotype to an environment does not correspond to organism fitness, but rather corresponds to maintaining the genome stability and integrity. In a stable environment, the phenotype maintains the stability of its originating genome and both (genome and phenotype) are reproduced identically. In an unstable environment (i.e., corresponding to variations in physicochemical parameters above a physiological range), the phenotype no longer maintains the stability of its originating genome, but instead influences its variations. Indeed, environment- and cellular-dependent physicochemical parameters define the probability of mutations in terms of frequency, nature, and location in a genome. Evolution is non-deterministic because it relies on probabilistic physicochemical rules, and evolution is driven by a bidirectional interplay between genome and phenotype in which the phenotype ensures the stability of its originating genome in a cellular and environmental physicochemical parameter-depending manner. Full article

(This article belongs to the Section Evolutionary Biology)

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28 pages, 6302 KiB

Open AccessEditor’s ChoiceReview

Synthetic Approaches for Nucleic Acid Delivery: Choosing the Right Carriers

by Rong Ni, Ruilu Feng and Ying Chau

Life 2019, 9(3), 59; https://doi.org/10.3390/life9030059 - 9 Jul 2019

Cited by 66 | Viewed by 9680

Abstract

The discovery of the genetic roots of various human diseases has motivated the exploration of different exogenous nucleic acids as therapeutic agents to treat these genetic disorders (inherited or acquired). However, the physicochemical properties of nucleic acids render them liable to degradation and [...] Read more.

The discovery of the genetic roots of various human diseases has motivated the exploration of different exogenous nucleic acids as therapeutic agents to treat these genetic disorders (inherited or acquired). However, the physicochemical properties of nucleic acids render them liable to degradation and also restrict their cellular entrance and gene translation/inhibition at the correct cellular location. Therefore, gene condensation/protection and guided intracellular trafficking are necessary for exogenous nucleic acids to function inside cells. Diversified cationic formulation materials, including natural and synthetic lipids, polymers, and proteins/peptides, have been developed to facilitate the intracellular transportation of exogenous nucleic acids. The chemical properties of different formulation materials determine their special features for nucleic acid delivery, so understanding the property–function correlation of the formulation materials will inspire the development of next-generation gene delivery carriers. Therefore, in this review, we focus on the chemical properties of different types of formulation materials and discuss how these formulation materials function as protectors and cellular pathfinders for nucleic acids, bringing them to their destination by overcoming different cellular barriers. Full article

(This article belongs to the Special Issue Modelling Life-Like Behavior in Systems Chemistry)

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14 pages, 324 KiB

Open AccessEditor’s ChoiceArticle

Molecular Diversity Required for the Formation of Autocatalytic Sets

by Wim Hordijk, Mike Steel and Stuart A. Kauffman

Life 2019, 9(1), 23; https://doi.org/10.3390/life9010023 - 1 Mar 2019

Cited by 20 | Viewed by 5861

Abstract

Systems chemistry deals with the design and study of complex chemical systems. However, such systems are often difficult to investigate experimentally. We provide an example of how theoretical and simulation-based studies can provide useful insights into the properties and dynamics of complex chemical [...] Read more.

Systems chemistry deals with the design and study of complex chemical systems. However, such systems are often difficult to investigate experimentally. We provide an example of how theoretical and simulation-based studies can provide useful insights into the properties and dynamics of complex chemical systems, in particular of autocatalytic sets. We investigate the issue of the required molecular diversity for autocatalytic sets to exist in random polymer libraries. Given a fixed probability that an arbitrary polymer catalyzes the formation of other polymers, we calculate this required molecular diversity theoretically for two particular models of chemical reaction systems, and then verify these calculations by computer simulations. We also argue that these results could be relevant to an origin of life scenario proposed recently by Damer and Deamer. Full article

(This article belongs to the Special Issue Modelling Life-Like Behavior in Systems Chemistry)

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17 pages, 36310 KiB

Open AccessEditor’s ChoiceReview

Bottom-Up Approaches to Synthetic Cooperation in Microbial Communities

by Daniel Rodríguez Amor and Martina Dal Bello

Life 2019, 9(1), 22; https://doi.org/10.3390/life9010022 - 26 Feb 2019

Cited by 45 | Viewed by 13427

Abstract

Microbial cooperation pervades ecological scales, from single-species populations to host-associated microbiomes. Understanding the mechanisms promoting the stability of cooperation against potential threats by cheaters is a major question that only recently has been approached experimentally. Synthetic biology has helped to uncover some of [...] Read more.

Microbial cooperation pervades ecological scales, from single-species populations to host-associated microbiomes. Understanding the mechanisms promoting the stability of cooperation against potential threats by cheaters is a major question that only recently has been approached experimentally. Synthetic biology has helped to uncover some of these basic mechanisms, which were to some extent anticipated by theoretical predictions. Moreover, synthetic cooperation is a promising lead towards the engineering of novel functions and enhanced productivity of microbial communities. Here, we review recent progress on engineered cooperation in microbial ecosystems. We focus on bottom-up approaches that help to better understand cooperation at the population level, progressively addressing the challenges of tackling higher degrees of complexity: spatial structure, multispecies communities, and host-associated microbiomes. We envisage cooperation as a key ingredient in engineering complex microbial ecosystems. Full article

(This article belongs to the Special Issue Synthetic Biology: From Living Computers to Terraformation)

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24 pages, 963 KiB

Open AccessEditor’s ChoiceReview

Unity Makes Strength: A Review on Mutualistic Symbiosis in Representative Insect Clades

by Rosario Gil and Amparo Latorre

Life 2019, 9(1), 21; https://doi.org/10.3390/life9010021 - 25 Feb 2019

Cited by 27 | Viewed by 7651

Abstract

Settled on the foundations laid by zoologists and embryologists more than a century ago, the study of symbiosis between prokaryotes and eukaryotes is an expanding field. In this review, we present several models of insect–bacteria symbioses that allow for the detangling of most [...] Read more.

Settled on the foundations laid by zoologists and embryologists more than a century ago, the study of symbiosis between prokaryotes and eukaryotes is an expanding field. In this review, we present several models of insect–bacteria symbioses that allow for the detangling of most known features of this distinctive way of living, using a combination of very diverse screening approaches, including molecular, microscopic, and genomic techniques. With the increasing the amount of endosymbiotic bacteria genomes available, it has been possible to develop evolutionary models explaining the changes undergone by these bacteria in their adaptation to the intracellular host environment. The establishment of a given symbiotic system can be a root cause of substantial changes in the partners’ way of life. Furthermore, symbiont replacement and/or the establishment of bacterial consortia are two ways in which the host can exploit its interaction with environmental bacteria for endosymbiotic reinvigoration. The detailed study of diverse and complex symbiotic systems has revealed a great variety of possible final genomic products, frequently below the limit considered compatible with cellular life, and sometimes with unanticipated genomic and population characteristics, raising new questions that need to be addressed in the near future through a wider exploration of new models and empirical observations. Full article

(This article belongs to the Special Issue Evolution of Mutualistic Symbiosis)

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12 pages, 2318 KiB

Open AccessEditor’s ChoiceArticle

Dynamical Task Switching in Cellular Computers

by Angel Goñi-Moreno, Fernando de la Cruz, Alfonso Rodríguez-Patón and Martyn Amos

Life 2019, 9(1), 14; https://doi.org/10.3390/life9010014 - 26 Jan 2019

Cited by 4 | Viewed by 5572

Abstract

We present a scheme for implementing a version of task switching in engineered bacteria, based on the manipulation of plasmid copy numbers. Our method allows for the embedding of multiple computations in a cellular population, whilst minimising resource usage inefficiency. We describe the [...] Read more.

We present a scheme for implementing a version of task switching in engineered bacteria, based on the manipulation of plasmid copy numbers. Our method allows for the embedding of multiple computations in a cellular population, whilst minimising resource usage inefficiency. We describe the results of computational simulations of our model, and discuss the potential for future work in this area. Full article

(This article belongs to the Special Issue Synthetic Biology: From Living Computers to Terraformation)

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18 pages, 3143 KiB

Open AccessEditor’s ChoiceArticle

Metatranscriptomic Analysis of the Bacterial Symbiont Dactylopiibacterium carminicum from the Carmine Cochineal Dactylopius coccus (Hemiptera: Coccoidea: Dactylopiidae)

by Rafael Bustamante-Brito, Arturo Vera-Ponce de León, Mónica Rosenblueth, Julio César Martínez-Romero and Esperanza Martínez-Romero

Life 2019, 9(1), 4; https://doi.org/10.3390/life9010004 - 3 Jan 2019

Cited by 18 | Viewed by 8130

Abstract

The scale insect Dactylopius coccus produces high amounts of carminic acid, which has historically been used as a pigment by pre-Hispanic American cultures. Nowadays carmine is found in food, cosmetics, and textiles. Metagenomic approaches revealed that Dactylopius spp. cochineals contain two Wolbachia strains, [...] Read more.

The scale insect Dactylopius coccus produces high amounts of carminic acid, which has historically been used as a pigment by pre-Hispanic American cultures. Nowadays carmine is found in food, cosmetics, and textiles. Metagenomic approaches revealed that Dactylopius spp. cochineals contain two Wolbachia strains, a betaproteobacterium named Candidatus Dactylopiibacterium carminicum and Spiroplasma, in addition to different fungi. We describe here a transcriptomic analysis indicating that Dactylopiibacterium is metabolically active inside the insect host, and estimate that there are over twice as many Dactylopiibacterium cells in the hemolymph than in the gut, with even fewer in the ovary. Albeit scarce, the transcripts in the ovaries support the presence of Dactylopiibacterium in this tissue and a vertical mode of transmission. In the cochineal, Dactylopiibacterium may catabolize plant polysaccharides, and be active in carbon and nitrogen provisioning through its degradative activity and by fixing nitrogen. In most insects, nitrogen-fixing bacteria are found in the gut, but in this study they are shown to occur in the hemolymph, probably delivering essential amino acids and riboflavin to the host from nitrogen substrates derived from nitrogen fixation. Full article

(This article belongs to the Special Issue Evolution of Mutualistic Symbiosis)

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