Light-controlled synthetic gene circuits

Highly complex synthetic gene circuits have been engineered in living organisms to develop systems with new biological properties. A precise trigger to activate or deactivate these complex systems is desired in order to tightly control different parts of a synthetic or natural network. Light represents an excellent tool to achieve this goal as it can be regulated in timing, location, intensity, and wavelength, which allows for precise spatiotemporal control over genetic circuits. Recently, light has been used as a trigger to control the biological function of small molecules, oligonucleotides, and proteins involved as parts in gene circuits. Light activation has enabled the construction of unique systems in living organisms such as band-pass filters and edge-detectors in bacterial cells. Additionally, light also allows for the regulation of intermediate steps of complex dynamic pathways in mammalian cells such as those involved in kinase networks. Herein we describe recent advancements in the area of light-controlled synthetic networks.     

Engineering and control of biological systems: A new way to tackle complex diseases

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health.     

Plant multiscale networks: charting plant connectivity by multi-level analysis and imaging techniques

In multicellular and even single-celled organisms, individual components are interconnected at multiscale levels to produce enormously complex biological networks that help these systems maintain homeostasis for development and environmental adaptation. Systems biology studies initially adopted network analysis to explore how relationships between individual components give rise to complex biological processes. Network analysis has been applied to dissect the complex connectivity of mammalian brains across different scales in time and space in The Human Brain Project. In plant science, network analysis has similarly been applied to study the connectivity of plant components at the molecular, subcellular, cellular, organic, and organism levels. Analysis of these multiscale networks contributes to our understanding of how genotype determines phenotype. In this review, we summarized the theoretical framework of plant multiscale networks and introduced studies investigating plant networks by various experimental and computational modalities. We next discussed the currently available analytic methodologies and multi-level imaging techniques used to map multiscale networks in plants. Finally, we highlighted some of the technical challenges and key questions remaining to be addressed in this emerging field.     

Robustness and evolvability in genetic regulatory networks

Living organisms are robust to a great variety of genetic changes. Gene regulation networks and metabolic pathways self-organize and reaccommodate to make the organism perform with stability and reliability under many point mutations, gene duplications and gene deletions. At the same time, living organisms are evolvable, which means that these kind of genetic perturbations can eventually make the organism acquire new functions and adapt to new environments. It is still an open problem to determine how robustness and evolvability blend together at the genetic level to produce stable organisms that yet can change and evolve. Here we address this problem by studying the robustness and evolvability of the attractor landscape of genetic regulatory network models under the process of gene duplication followed by divergence. We show that an intrinsic property of this kind of networks is that, after the divergence of the parent and duplicate genes, with a high probability the previous phenotypes, encoded in the attractor landscape of the network, are preserved and new ones might appear. The above is true in a variety of network topologies and even for the case of extreme divergence in which the duplicate gene bears almost no relation with its parent. Our results indicate that networks operating close to the so-called "critical regime" exhibit the maximum robustness and evolvability simultaneously.     

Non-destructive genotyping and genetic variation of fanning in a honey bee colony

The relationship between workers from different patrilines in a naturally mated queen honey bee colony is very complex due to queen polyandry, and still poorly characterized. Here, we report a means of determining the genotype of living workers in a natural honey bee colony by a new non-destructive method, which makes it possible to observe the relationship between behaviours and genotypes. DNA was extracted from the exuvia, found at the bottom of each brood cell, and confirmed to be identical to the DNA extracted from the thorax muscle of the bee emerging from that particular cell. The genotypes were thus determined using DNA from the exuviae without having to hurt or kill the organisms. The emerging workers were marked with coloured, numbered tags to enable behavioural observations over their entire life. Using this new method, we determined 20 patrilines in a naturally mated queen colony, and discovered that the patriline composition of bees exhibiting fanning behaviour was significantly different from the patriline composition of the whole colony. Our results confirm that the genetic structure of a natural insect society plays a fundamental role in the division of labour. The new non-destructive method reveals a novel avenue for the determination of relationships between the behaviours and genes of social insects.     

Sensing the environment: lessons from fungi

All living organisms use numerous signal-transduction systems to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we review recent progress in our understanding of how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental cues.     

Oligosaccharide microarrays for glycomics

Glycomics is an emerging field that was proposed at the end of the 20th century as a new concept to follow genomics and proteomics. Studies on glycans are indispensable to define complex life systems and cell communities because all living organisms consist of diverse cells, which are covered with an abundance of heterogeneous carbohydrates. Although studies on glycans are extremely difficult because of the lack of basic technologies common to DNAs and proteins, a few new aspects of glycotechnologies have now become realized in the form of "bio-chips", which include "oligosaccharide arrays" or "glyco-chips". Recently, Fukui et al. developed oligosaccharide microarrays for glycomic analysis of extensive carbohydrate-binding proteins. How and why such glyco-engineering projects have been made in the contexts of both pure and applied sciences is described.     

Thioredoxins, glutaredoxins, and glutathionylation: new crosstalks to explore

Oxidants are widely considered as toxic molecules that cells have to scavenge and detoxify efficiently and continuously. However, emerging evidence suggests that these oxidants can play an important role in redox signaling, mainly through a set of reversible post-translational modifications of thiol residues on proteins. The most studied redox system in photosynthetic organisms is the thioredoxin (TRX) system, involved in the regulation of a growing number of target proteins via thiol/disulfide exchanges. In addition, recent studies suggest that glutaredoxins (GRX) could also play an important role in redox signaling especially by regulating protein glutathionylation, a post-translational modification whose importance begins to be recognized in mammals while much less is known in photosynthetic organisms. This review focuses on oxidants and redox signaling with particular emphasis on recent developments in the study of functions, regulation mechanisms and targets of TRX, GRX and glutathionylation. This review will also present the complex emerging interplay between these three components of redox-signaling networks.Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

Signaling and gene regulatory programs in plant vascular stem cells

A key question about the development of multicellular organisms is how they precisely control the complex pattern formation during their growth. For plants to grow for many years, a tight balance between pluripotent dividing cells and cells undergoing differentiation should be maintained within stem cell populations. In this process, cell-cell communication plays a central role by creating positional information for proper cell type patterning. Cell-type specific gene regulatory networks govern differentiation of cells into particular cell types. In this review, we will provide a comprehensive overview of emerging key signaling and regulatory programs in the stem cell population that direct morphogenesis of plant vascular tissues.     

Synthetic therapeutic gene circuits in mammalian cells

In the emerging field of synthetic biology, scientists are focusing on designing and creating functional devices, systems, and organisms with novel functions by engineering and assembling standardised biological building blocks. The progress of synthetic biology has significantly advanced the design of functional gene networks that can reprogram metabolic activities in mammalian cells and provide new therapeutic opportunities for future gene- and cell-based therapies. In this review, we describe the most recent advances in synthetic mammalian gene networks designed for biomedical applications, including how these synthetic therapeutic gene circuits can be assembled to control signalling networks and applied to treat metabolic disorders, cancer, and immune diseases. We conclude by discussing the various challenges and future prospects of using synthetic mammalian gene networks for disease therapy.     

De Novo Evolution of Complex, Global and Hierarchical Gene Regulatory Mechanisms

Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems.     

Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram

Background  

With an accumulation of in silico data obtained by simulating large-scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells.     

The role of global trade and transport network topology in the human‐mediated dispersal of alien species

More people and goods are moving further and more frequently via many different trade and transport networks under current trends of globalisation. These networks can play a major role in the unintended introduction of exotic species to new locations. With the continuing rise in global trade, more research attention is being focused on the role of networks in the spread of invasive species. This represents an emerging field of research in invasion science and the substantial knowledge being generated within other disciplines can provide ecologists with new tools with which to study invasions. For the first time, we synthesise studies from several perspectives, approaches and disciplines to derive the fundamental characteristics of network topology determining the likelihood of spread of organisms via trade and transport networks. These characteristics can be used to identify critical points of vulnerability within these networks and enable the development of more effective strategies to prevent invasions.     

The use of nanocrystals in biological detection

In the coming decade, the ability to sense and detect the state of biological systems and living organisms optically, electrically and magnetically will be radically transformed by developments in materials physics and chemistry. The emerging ability to control the patterns of matter on the nanometer length scale can be expected to lead to entirely new types of biological sensors. These new systems will be capable of sensing at the single-molecule level in living cells, and capable of parallel integration for detection of multiple signals, enabling a diversity of simultaneous experiments, as well as better crosschecks and controls.