{"title":"Adaptive circuits in synthetic biology","authors":"Timothy Frei, Mustafa Khammash","doi":"10.1016/j.coisb.2021.100399","DOIUrl":"10.1016/j.coisb.2021.100399","url":null,"abstract":"<div><p>One of the most remarkable features of biological systems is their ability to adapt to the constantly changing environment. By harnessing principles of control theory, synthetic biologists are starting to mimic this adaptation in regulatory gene circuits. Doing so allows for the construction of systems that perform reliably under non-optimal conditions. Furthermore, making a system adaptive can make up for imperfect knowledge of the underlying biology and, hence, avoid unforeseen complications in the implementation. Here, we review recent developments in the analysis and implementation of adaptive regulatory networks in synthetic biology with a particular focus on genetic circuits that can realize perfect adaptation.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000949/pdfft?md5=4663c6a4dfdd14bb5c0f9f4d6841b62d&pid=1-s2.0-S2452310021000949-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42758680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Markus Ralser , Sreejith J. Varma , Richard A. Notebaart
{"title":"The evolution of the metabolic network over long timelines","authors":"Markus Ralser , Sreejith J. Varma , Richard A. Notebaart","doi":"10.1016/j.coisb.2021.100402","DOIUrl":"10.1016/j.coisb.2021.100402","url":null,"abstract":"<div><p>Metabolism is executed by an efficient, interconnected and ancient biochemical system, the metabolic network. Its evolutionary origins are, however, barely understood. We here discuss that because of niche adaptation, the evolutionary selection acting on the metabolic network structure distinguishes modern species and early life forms. Yet, its basic structure remained conserved over more than three billion years of diverging evolution. We speculate that this situation attributes key roles in metabolic network evolution to (i) the reaction properties of central metabolites, (ii) simple catalysts (e.g. metal ions, amino acids) whose importance remained unchanged during evolution, and (iii) the interconnectivity of the network that limits its expansion. The conservation of network structure hence implies that early life forms already used similar metabolic reaction topologies as modern species.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000974/pdfft?md5=4bad2063148f98b62f38ae026e235900&pid=1-s2.0-S2452310021000974-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47343395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering programmable RNA synthetic circuits in mammalian cells","authors":"Federica Cella, Ilaria De Martino , Francesca Piro , Velia Siciliano","doi":"10.1016/j.coisb.2021.100395","DOIUrl":"10.1016/j.coisb.2021.100395","url":null,"abstract":"<div><p><span>The ability to reprogram mammalian cells with tight spatiotemporal control </span>over gene expression<span> and cell response has provided a powerful means to address biomedical challenges. To provide safer synthetic biology products, RNA<span> has recently emerged as an alternative to DNA to deliver transgenes into mammalian cells. In this review, we discuss recent tools implemented to engineer programmable RNA-based synthetic circuits in mammalian cells. We examine the limitations of RNA-encoded gene delivery, and we highlight significant studies that successfully improved payloads expression and persistence and maximized RNA delivery efficiency. Finally, we conclude by discussing examples of RNA-based therapeutics and future perspectives.</span></span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49554071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Johanna Jaekel, David Schweingruber, Vasileios Cheras, Jiten Doshi, Yaakov Benenson
{"title":"Multi-input biocomputer gene circuits for therapeutic application","authors":"Judith Johanna Jaekel, David Schweingruber, Vasileios Cheras, Jiten Doshi, Yaakov Benenson","doi":"10.1016/j.coisb.2021.100371","DOIUrl":"10.1016/j.coisb.2021.100371","url":null,"abstract":"<div><p>Clinical approvals of gene and cell therapies in recent years, and advances in our ability to engineer complex cellular functions using synthetic biology have fueled interest in merging these two approaches to develop and deploy ever more sophisticated treatments. One area of interface between synthetic biology tools and therapeutics comprises synthetic gene circuits that ‘compute’ a response in a programmable fashion using multiple biomolecular inputs. The potential therapeutic utility of such circuits hinges on their ability to perform logical integration of inputs linked to the human cell phenotype. AND logic increases response specificity, OR logic enables targeting heterogeneous cell populations, and NOT logic provides additional safety. We review recent efforts to implement input sensing and logical integration capabilities in cell, gene, RNA, and microbiome-based therapies. With therapeutic candidates using biomolecular computation already in clinical trials, the approach is poised to revolutionize the field of advanced therapies in the years to come.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43649718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthetic biology-based optogenetic approaches to control therapeutic designer cells","authors":"Maysam Mansouri , Martin Fussenegger","doi":"10.1016/j.coisb.2021.100396","DOIUrl":"10.1016/j.coisb.2021.100396","url":null,"abstract":"<div><p>Optogenetics uses light as a traceless inducer to remotely control cellular behavior with high safety and spatiotemporal precision, and its implementation for therapeutic synthetic biology enable customizable user-defined remedial outputs to be generated from suitably engineered cells. Here, we focus on non-neural optogenetics, describing the tools and strategies available to engineer light-responsive, therapeutic mammalian designer cells and highlighting recent advances in design and translational applications, including cell and gene therapies. We also discuss current limitations in engineering genetically encoded light-sensitive systems and suggest some possible solutions.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000913/pdfft?md5=7904dcf7df39ed3f040ba8e89584ddda&pid=1-s2.0-S2452310021000913-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48042013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Click it or stick it: Covalent and non-covalent methods for protein-self assembly","authors":"Oskar J. Lange, Karen M. Polizzi","doi":"10.1016/j.coisb.2021.100374","DOIUrl":"10.1016/j.coisb.2021.100374","url":null,"abstract":"<div><p>Protein complexes<span> are ubiquitous in living systems and have a range of biotechnological applications. However, building protein structures from scratch can be a difficult and laborious process. Here, we review recent developments in protein self-assembly, including a range of tools for covalent and non-covalent assembly of protein structures with user-defined architectures. Key achievements in covalent protein assembly include the development of systems with fast reaction rates and nM affinities. Non-covalent assembly methods have lagged because of the complexity of natural interactions governing protein assembly; but recent developments have created modular methods that are more broadly applicable. On the horizon, we foresee an increasing role for computational protein design tools as key in cementing the role of applications, as opposed to methodology, as the main driving force of research in this field.</span></p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48136963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Erratum to “Regarding missing Editorial Disclosure statements in previously published articles” – Part I","authors":"","doi":"10.1016/j.coisb.2021.100387","DOIUrl":"10.1016/j.coisb.2021.100387","url":null,"abstract":"","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452310021000822/pdfft?md5=54855021c605f6e9a282ea9963bb0b2d&pid=1-s2.0-S2452310021000822-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48205074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dynamic models for metabolomics data integration","authors":"Polina Lakrisenko , Daniel Weindl","doi":"10.1016/j.coisb.2021.100358","DOIUrl":"10.1016/j.coisb.2021.100358","url":null,"abstract":"<div><p>As metabolomics datasets are becoming larger and more complex, there is an increasing need for model-based data integration and analysis to optimally leverage these data. Dynamic models of metabolism allow for the integration of heterogeneous data and the analysis of dynamic phenotypes. Here, we review recent efforts in using dynamic metabolic models for data integration, focusing on approaches based on ordinary differential equations that are applicable to both time-resolved and steady-state measurements and that do not require flux distributions as inputs. Furthermore, we discuss recent advances and current challenges. We conclude that much progress has been made in various areas, such as the development of scalable simulation tools, and although challenges remain, dynamic modeling is a powerful tool for metabolomics data analysis that is not yet living up to its full potential.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44755827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cameron D. McBride , Theodore W. Grunberg , Domitilla Del Vecchio
{"title":"Design of genetic circuits that are robust to resource competition","authors":"Cameron D. McBride , Theodore W. Grunberg , Domitilla Del Vecchio","doi":"10.1016/j.coisb.2021.100357","DOIUrl":"10.1016/j.coisb.2021.100357","url":null,"abstract":"<div><p>The ability to engineer genetic circuits in living cells has tremendous potential in many applications, from health, to energy, to bio-manufacturing. Although substantial efforts have gone into design approaches that make circuits robust to variable cellular context, context dependence of genetic circuits remains a significant hurdle. We review intra-cellular resource competition, one culprit of context dependence, and summarize recent efforts toward design approaches to mitigate it. We classify these approaches into two main groups: global control and local control. In the former, the pool of resources is regulated to meet the demand, and in the latter, individual modules are regulated to be robust to variability in the pool of resources. Within each group, we highlight both feedback and feedforward implementations.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47057967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kate E. Dray , Hailey I. Edelstein , Kathleen S. Dreyer , Joshua N. Leonard
{"title":"Control of mammalian cell-based devices with genetic programming","authors":"Kate E. Dray , Hailey I. Edelstein , Kathleen S. Dreyer , Joshua N. Leonard","doi":"10.1016/j.coisb.2021.100372","DOIUrl":"10.1016/j.coisb.2021.100372","url":null,"abstract":"<div><p><span>Synthetic biology increasingly enables the construction of sophisticated functions in mammalian cells. A particularly promising frontier combines concepts drawn from industrial process control engineering — which is used to confer and balance properties such as stability and efficiency — with understanding as to how living systems have evolved to perform similar tasks with biological components. In this review, we first survey the state-of-the-art for both technologies and strategies available for </span>genetic programming in mammalian cells. We then discuss recent progress in implementing programming objectives inspired by engineered and natural control mechanisms. Finally, we consider the transformative role of model-guided design in the present and future construction of customized mammalian cell functions for applications in biotechnology, medicine, and fundamental research.</p></div>","PeriodicalId":37400,"journal":{"name":"Current Opinion in Systems Biology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.coisb.2021.100372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39420648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}