scholarly journals Nanoscale programming of cellular and physiological phenotypes: inorganic meets organic programming

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Nikolay V. Dokholyan

AbstractThe advent of protein design in recent years has brought us within reach of developing a “nanoscale programing language,” in which molecules serve as operands with their conformational states functioning as logic gates. Combining these operands into a set of operations will result in a functional program, which is executed using nanoscale computing agents (NCAs). These agents would respond to any given input and return the desired output signal. The ability to utilize natural evolutionary processes would allow code to “evolve” in the course of computation, thus enabling radically new algorithmic developments. NCAs will revolutionize the studies of biological systems, enable a deeper understanding of human biology and disease, and facilitate the development of in situ precision therapeutics. Since NCAs can be extended to novel reactions and processes not seen in biological systems, the growth of this field will spark the growth of biotechnological applications with wide-ranging impacts, including fields not typically considered relevant to biology. Unlike traditional approaches in synthetic biology that are based on the rewiring of signaling pathways in cells, NCAs are autonomous vehicles based on single-chain proteins. In this perspective, I will introduce and discuss this new field of biological computing, as well as challenges and the future of the NCA. Addressing these challenges will provide a significant leap in technology for programming living cells.

2020 ◽  
Vol 154 (2) ◽  
pp. 135-153 ◽  
Author(s):  
Gabriel García Caballero ◽  
Donella Beckwith ◽  
Nadezhda V. Shilova ◽  
Adele Gabba ◽  
Tanja J. Kutzner ◽  
...  

Abstract The concept of biomedical significance of the functional pairing between tissue lectins and their glycoconjugate counterreceptors has reached the mainstream of research on the flow of biological information. A major challenge now is to identify the principles of structure–activity relationships that underlie specificity of recognition and the ensuing post-binding processes. Toward this end, we focus on a distinct feature on the side of the lectin, i.e. its architecture to present the carbohydrate recognition domain (CRD). Working with a multifunctional human lectin, i.e. galectin-3, as model, its CRD is used in protein engineering to build variants with different modular assembly. Hereby, it becomes possible to compare activity features of the natural design, i.e. CRD attached to an N-terminal tail, with those of homo- and heterodimers and the tail-free protein. Thermodynamics of binding disaccharides proved full activity of all proteins at very similar affinity. The following glycan array testing revealed maintained preferential contact formation with N-acetyllactosamine oligomers and histo-blood group ABH epitopes irrespective of variant design. The study of carbohydrate-inhibitable binding of the test panel disclosed up to qualitative cell-type-dependent differences in sections of fixed murine epididymis and especially jejunum. By probing topological aspects of binding, the susceptibility to inhibition by a tetravalent glycocluster was markedly different for the wild-type vs the homodimeric variant proteins. The results teach the salient lesson that protein design matters: the type of CRD presentation can have a profound bearing on whether basically suited oligosaccharides, which for example tested positively in an array, will become binding partners in situ. When lectin-glycoconjugate aggregates (lattices) are formed, their structural organization will depend on this parameter. Further testing (ga)lectin variants will thus be instrumental (i) to define the full range of impact of altering protein assembly and (ii) to explain why certain types of design have been favored during the course of evolution, besides opening biomedical perspectives for potential applications of the novel galectin forms.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ximing Li ◽  
Luna Rizik ◽  
Valeriia Kravchik ◽  
Maria Khoury ◽  
Netanel Korin ◽  
...  

AbstractComplex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial neural networks, comprised of flexible interactions for computation, support adaptive designs and are adopted for diverse applications. Here, motivated by the structural similarity between artificial neural networks and cellular networks, we implement neural-like computing in bacteria consortia for recognizing patterns. Specifically, receiver bacteria collectively interact with sender bacteria for decision-making through quorum sensing. Input patterns formed by chemical inducers activate senders to produce signaling molecules at varying levels. These levels, which act as weights, are programmed by tuning the sender promoter strength Furthermore, a gradient descent based algorithm that enables weights optimization was developed. Weights were experimentally examined for recognizing 3 × 3-bit pattern.


Metabolites ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 76 ◽  
Author(s):  
Farhana R. Pinu ◽  
David J. Beale ◽  
Amy M. Paten ◽  
Konstantinos Kouremenos ◽  
Sanjay Swarup ◽  
...  

The use of multiple omics techniques (i.e., genomics, transcriptomics, proteomics, and metabolomics) is becoming increasingly popular in all facets of life science. Omics techniques provide a more holistic molecular perspective of studied biological systems compared to traditional approaches. However, due to their inherent data differences, integrating multiple omics platforms remains an ongoing challenge for many researchers. As metabolites represent the downstream products of multiple interactions between genes, transcripts, and proteins, metabolomics, the tools and approaches routinely used in this field could assist with the integration of these complex multi-omics data sets. The question is, how? Here we provide some answers (in terms of methods, software tools and databases) along with a variety of recommendations and a list of continuing challenges as identified during a peer session on multi-omics integration that was held at the recent ‘Australian and New Zealand Metabolomics Conference’ (ANZMET 2018) in Auckland, New Zealand (Sept. 2018). We envisage that this document will serve as a guide to metabolomics researchers and other members of the community wishing to perform multi-omics studies. We also believe that these ideas may allow the full promise of integrated multi-omics research and, ultimately, of systems biology to be realized.


Sensors ◽  
2020 ◽  
Vol 20 (20) ◽  
pp. 5905
Author(s):  
Paul D. Rosero-Montalvo ◽  
Vanessa C. Erazo-Chamorro ◽  
Vivian F. López-Batista ◽  
María N. Moreno-García ◽  
Diego H. Peluffo-Ordóñez

This work presents a monitoring system for the environmental conditions of rose flower-cultivation in greenhouses. Its main objective is to improve the quality of the crops while regulating the production time. To this end, a system consisting of autonomous quadruped vehicles connected with a wireless sensor network (WSN) is developed, which supports the decision-making on type of action to be carried out in a greenhouse to maintain the appropriate environmental conditions for rose cultivation. A data analysis process was carried out, aimed at designing an in-situ intelligent system able to make proper decisions regarding the cultivation process. This process involves stages for balancing data, prototype selection, and supervised classification. The proposed system produces a significant reduction of data in the training set obtained by the WSN while reaching a high classification performance in real conditions—amounting to 90% and 97.5%, respectively. As a remarkable outcome, it is also provided an approach to ensure correct planning and selection of routes for the autonomous vehicle through the global positioning system.


2014 ◽  
Vol 111 (8) ◽  
pp. 1566-1576 ◽  
Author(s):  
Kristina Meier ◽  
Frederike Carstensen ◽  
Christoph Scheeren ◽  
Lars Regestein ◽  
Matthias Wessling ◽  
...  

2013 ◽  
Vol 791-793 ◽  
pp. 1845-1849
Author(s):  
Xu Dong Fang ◽  
Yu Hua Tang ◽  
Jun Jie Wu

With the realization of physical memristors, using memristors to perform stateful logic operations has been demonstrated feasible. In such operations, memristors simultaneously serve as latches and logic gates, thus enabling the in-situ computing which may open a new computing paradigm for computer architecture. In this paper, we first analyze two types of typical memristive stateful logic gates to reveal the working mechanism of the stateful logic, and then review the recent researches on the memristive stateful logic, and finally discuss the pros and cons of the stateful logic. We reach the conclusion that the stateful logic promises a novel computing paradigm which may revolutionize the conventional computer architecture, while its development is currently subjected to the state drift problem and is constrained by the lack of a general design methodology and physically verification.


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