Distributed biological computation with multicellular engineered networks

Sense and sensibility: of synthetic biology and the redesign of bioreporter circuits.

Simple SummaryThis review provides a roadmap to develop safe and effective OV-based future therapeutics by using several novel synthetic and system biology strategies. Integration of system and synthetic biology can improve the genetic design of OVs backbone, maintaining enough virulence-associated genes. Furthermore, specific computation pipelines can refine target discovery in several types of cancer, identifying the MHC-I and II-restricted peptide repertoire recognized by T-cells and reinforcing anticancer immune responses. Using these versatile approaches could encourage the development of a next-generation of OVs-based therapies, overcoming current challenges such as on-target, off-tumor effects, and variable clinical responses. The efficacy and safety profile of the current OVs-based regimens could be further enhanced with additional long-lasting clinical effects.Oncolytic virus (OV)-based immunotherapy is mainly dependent on establishing an efficient cell-mediated antitumor immunity. OV-mediated antitumor immunity elicits a renewed antitumor reactivity, stimulating a T-cell response against tumor-associated antigens (TAAs) and recruiting natural killer cells within the tumor microenvironment (TME). Despite the fact that OVs are unspecific cancer vaccine platforms, to further enhance antitumor immunity, it is crucial to identify the potentially immunogenic T-cell restricted TAAs, the main key orchestrators in evoking a specific and durable cytotoxic T-cell response. Today, innovative approaches derived from systems biology are exploited to improve target discovery in several types of cancer and to identify the MHC-I and II restricted peptide repertoire recognized by T-cells. Using specific computation pipelines, it is possible to select the best tumor peptide candidates that can be efficiently vectorized and delivered by numerous OV-based platforms, in order to reinforce anticancer immune responses. Beyond the identification of TAAs, system biology can also support the engineering of OVs with improved oncotropism to reduce toxicity and maintain a sufficient portion of the wild-type virus virulence. Finally, these technologies can also pave the way towards a more rational design of armed OVs where a transgene of interest can be delivered to TME to develop an intratumoral gene therapy to enhance specific immune stimuli.

Paving the way for synthetic biology‐based bioremediation in Europe

Multi-level fluorescent logic gate based on polyamine coated carbon dots capable of responding to four stimuli

Ongoing efforts within neuroscience and intelligent system have been directed toward the building of artificial computational models using simulated neuron units as basic building blocks. Such efforts, inspired in the standard design of traditional neural networks, are limited by the difficulties arising from single functional performance and computational inconvenience, especially when modeling large scale, complex and dynamic processes such as cognitive recognition. Here, we show that there is a different form of implementing cortex-like mechanism, the motivation comes directly from recent pioneering works on detailed functional decomposition analysis of the visual cortex and developments on spiking neural networks (SNNs), a promising direction for neural networks, as they utilize information representation as trains of spikes, embedded with spatiotemporal characteristics. A practical implementation is presented, which can be simply described as cortical-like feed-forward hierarchy using biologically plausible neural system. As a proof of principle, a prototype model has been testified on the platform of several facial expression dataset. Of note, small structure modifications and different learning schemes allow for implementing more complicated decision system, showing great potential for discovering implicit pattern of interest and further analysis. Our results support the approach of using such hierarchical consortia as an efficient way of complex pattern analysis task not easily solvable using traditional, single functional way of implementations.

The miniaturization of the devices into nanoscale has enabled ultra high density chips, but at the cost of increased defect density. In this manuscript, Markov Random Field (MRF) approach is used to evaluate the device reliability in the presence of high defect density. Both hard and soft errors have been considered. We have presented a NANOLAB based fault model of 8-bit full adder, basic building block being 2:1 multiplexer. At each level, a Triple Modular Redundancy (TMR) is employed to enhance reliability. The results are compared with another 8-bit full adder, designed using logic gates. Assuming defect rate up to 10%, the circuits are evaluated for stuck at faults. Further, we have augmented the NANOLAB tool to include a design library of various types of flip flops. A 4-bit SISO right shift register is used as vehicle for exemplifying our approach. The fault tolerant approach N-Modular Redundancy (NMR) is compared at different levels of granularity and for varying levels of N. It is observed that NMR fails to provide the device fault tolerance when defect rate is higher than a threshold value.

In this study, we propose complementary metal-oxide−semiconductor (CMOS) NOR logic gates consisting of silicon nanowire (NW) arrays on bendable substrates. A circuit consisting of two p-channel NW field-effect transistors (NWFETs) in series and two n-channel NWFETs in parallel is constructed to operate a two-input CMOS NOR logic gate. The NOR logic gates operate at a low supply voltage of 1 V with a rail-to-rail logic swing and a high voltage gain of approximately −3.0. The exact NOR logic functionality is achieved owing to the superior electrical characteristics of the well-aligned p- and n-NWFETs, which are obtained using conventional Si-based CMOS technology. Moreover, the NOR logic gates exhibit stable characteristics and have good mechanical properties. The proposed bendable NW CMOS NOR logic gates are promising building blocks for future bendable integrated electronics.

In this article I address the interactions between biological knowledge and ideas about the kinds of entity that are suited to appropriation. I start by arguing that commodification and reductionism are closely linked, and that patenting suits entities that are discrete and isolable, such as those that are the focus of molecular biology. I then turn to the new field of systems biology, which recognizes that traditional reductionist approaches to biology are no longer adequate and attempts to provide a more integrative understanding of biological systems. In doing this, systems biology has to deal with emergent phenomena. But patenting does not suit the dynamic and interactive complexity that is the object of study in systems biology. If systems biology rejects reductionism where does that leave commodification? I examine attempts to commodify predictive computational models in systems biology. I then turn to systems biology's sister discipline, synthetic biology, which deals with emergence by reducing the complexity of biological systems. By factoring out messy contingencies, synthetic biology is, in theory, well suited to commodification. Drawing on both these examples I explore how ideas about appropriation, including open source, are influencing the nature and course of research in biology.

Chapter 1 - Systems biology, synthetic biology, and metabolic engineering

Electronically controllable neuristor based logic gates and their applications

Electromechanical computing based on micro/nano resonators has recently attracted significant attention. However, full implementation of this technology has been hindered by the difficulty in realizing complex logic circuits. We report here an alternative approach to realize complex logic circuits based on multiple MEMS resonators. As case studies, we report the construction of a single-bit binary comparator, a single-bit 4-to-2 encoder, and parallel XOR/XNOR and AND/NOT logic gates. Toward this, several microresonators are electrically connected and their resonance frequencies are tuned through an electrothermal modulation scheme. The microresonators operating in the linear regime do not require large excitation forces, and work at room temperature and at modest air pressure. This study demonstrates that by reconfiguring the same basic building block, tunable resonator, several essential complex logic functions can be achieved.

Biologists have used a reductionist approach to investigate the essence of life. In the last years, scientific disciplines have merged with the aim of studying life on a global scale in terms of molecules and their interactions. Based on high-throughput measurements, Systems Biology adopts mathematical modeling and computational simulation to reconstruct natural biological systems. Synthetic Biology seeks to engineer artificial biological systems starting from standard molecular compounds coding in DNA. Can Systems and Synthetic Biology be combined with the idea of creating a new science—‘SYS Biology’ that will not demarcate natural and artificial realities? What will this approach bring to medicine?

Calculating life? Duelling discourses in interdisciplinary systems biology

The central aim of synthetic biology is to create and exploit biological processes that do not occur naturally. In many cases this will involve one or more steps in genetic engineering to create an organism that so far has not been found in nature. In contrast, systems biology aims to describe biological processes in their entirety, be it the complete genome of an organism, community or ecosystem, or the processes occurring in such biological systems. Systems biology adopts a top-down approach; in contrast, synthetic biology requires a bottom-up approach: first a problem is identified; data from many possible sources, including systems biology, can then be searched for possible solutions. The current thematic issue explores some of the applications of synthetic biology. While systems biology strives to provide a complete description of what is available naturally, synthetic biology exploits this information to design solutions to a specific problem. The study by Quirino and Beier nicely illustrates this principle. It is just one of the contributions to this thematic issue that originated from poster or lecture presentations during the 5th FEMS Congress of Microbiology held in Leipzig in July 2013. Our scope was limited by an unexpected paucity of contributions in Leipzig exploring exciting contributions being made across Europe, for example, to the use of synthetic biology to generate replacements for naturally synthesized antibiotics. Also in strikingly low abundance were presentations on small RNAs: their global occurrence; their roles in the regulation of gene expression; and their potential for medical exploitation as antisense RNA. We are therefore pleased to include the article by Philipps et al . ‘Expression of Porphyromonas gingivalis small RNA in response to hemin availability identified using microarray and RNA-seq analysis’. Genetic engineering is undoubtedly one of the cornerstones of synthetic biology, not least for the production of recombinant …

Over the last few decades reconstructive surgery and general medicine has shifted from a resection-oriented approach towards strategies focusing on the repair and regeneration of tissues. Artificial tissue substitutes containing metals, ceramics and polymers, to maintain skeletal function [6], and artificial devices, such as pacemakers and insulin pumps, have been used to reach this goal. These artificial materials and devices have significantly improved the possibility for clinicians to restore the form and, to some extent, the function of defective bones as well as to increased life expectancy of patients, e.g. with valvular heart disease or diabetes mellitus. Despite the fact that every artificial device has specific disadvantages, the use of biomaterials is currently a common treatment option in clinical practice. More detailed understanding exists concerning the transplantation of cells and tissues; thus, autografts are the second mainstay in clinical practice. The advantages of transplanting the body’s own tissues ensure that autograft tissue transplantation can now be considered to be the “gold standard” in bone reconstruction. The reason for the primacy of tissue grafts over non-living biomaterials is that they contain living cells, thus possessing biological activity. The main disadvantages of using autografts are donor site morbidity and donor shortage [19]. Research is currently in progress into the use of cell-based approaches in reconstructive surgery, since cells are the driving elements for all repair and regeneration processes. As they synthesize and assemble the extracellular matrix, cells can be considered the basic unit needed for a biological regeneration strategy.