{"title":"自组织多细胞结构的合成抑制回路的数学和硅学分析。","authors":"Calvin Lam*, ","doi":"10.1021/acssynbio.4c00230","DOIUrl":null,"url":null,"abstract":"<p >Bottom-up approaches are becoming increasingly popular for studying multicellular self-organization and development. In contrast to the classic top-down approach, where parts of the organization/developmental process are broken to understand the process, the goal is to build the process to understand it. For example, synthetic circuits have been built to understand how cell–cell communication and differential adhesion can drive multicellular development. The majority of current bottom-up efforts focus on using activatory circuits to engineer and understand development, but efforts with inhibitory circuits have been minimal. Yet, inhibitory circuits are ubiquitous and vital to native developmental processes. Thus, inhibitory circuits are a crucial yet poorly studied facet of bottom-up multicellular development. To demonstrate the potential of inhibitory circuits for building and developing multicellular structures, several synthetic inhibitory circuits that combine engineered cell–cell communication and differential adhesion were designed, and then examined for synthetic development capability using a previously validated in silico framework. These designed inhibitory circuits can build a variety of patterned, self-organized structures and even morphological oscillations. These results support that inhibitory circuits can be powerful tools for building, studying, and understanding developmental processes.</p>","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mathematical and In Silico Analysis of Synthetic Inhibitory Circuits That Program Self-Organizing Multicellular Structures\",\"authors\":\"Calvin Lam*, \",\"doi\":\"10.1021/acssynbio.4c00230\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Bottom-up approaches are becoming increasingly popular for studying multicellular self-organization and development. In contrast to the classic top-down approach, where parts of the organization/developmental process are broken to understand the process, the goal is to build the process to understand it. For example, synthetic circuits have been built to understand how cell–cell communication and differential adhesion can drive multicellular development. The majority of current bottom-up efforts focus on using activatory circuits to engineer and understand development, but efforts with inhibitory circuits have been minimal. Yet, inhibitory circuits are ubiquitous and vital to native developmental processes. Thus, inhibitory circuits are a crucial yet poorly studied facet of bottom-up multicellular development. To demonstrate the potential of inhibitory circuits for building and developing multicellular structures, several synthetic inhibitory circuits that combine engineered cell–cell communication and differential adhesion were designed, and then examined for synthetic development capability using a previously validated in silico framework. These designed inhibitory circuits can build a variety of patterned, self-organized structures and even morphological oscillations. These results support that inhibitory circuits can be powerful tools for building, studying, and understanding developmental processes.</p>\",\"PeriodicalId\":26,\"journal\":{\"name\":\"ACS Synthetic Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Synthetic Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acssynbio.4c00230\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Synthetic Biology","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acssynbio.4c00230","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Mathematical and In Silico Analysis of Synthetic Inhibitory Circuits That Program Self-Organizing Multicellular Structures
Bottom-up approaches are becoming increasingly popular for studying multicellular self-organization and development. In contrast to the classic top-down approach, where parts of the organization/developmental process are broken to understand the process, the goal is to build the process to understand it. For example, synthetic circuits have been built to understand how cell–cell communication and differential adhesion can drive multicellular development. The majority of current bottom-up efforts focus on using activatory circuits to engineer and understand development, but efforts with inhibitory circuits have been minimal. Yet, inhibitory circuits are ubiquitous and vital to native developmental processes. Thus, inhibitory circuits are a crucial yet poorly studied facet of bottom-up multicellular development. To demonstrate the potential of inhibitory circuits for building and developing multicellular structures, several synthetic inhibitory circuits that combine engineered cell–cell communication and differential adhesion were designed, and then examined for synthetic development capability using a previously validated in silico framework. These designed inhibitory circuits can build a variety of patterned, self-organized structures and even morphological oscillations. These results support that inhibitory circuits can be powerful tools for building, studying, and understanding developmental processes.
期刊介绍:
The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism.
Topics may include, but are not limited to:
Design and optimization of genetic systems
Genetic circuit design and their principles for their organization into programs
Computational methods to aid the design of genetic systems
Experimental methods to quantify genetic parts, circuits, and metabolic fluxes
Genetic parts libraries: their creation, analysis, and ontological representation
Protein engineering including computational design
Metabolic engineering and cellular manufacturing, including biomass conversion
Natural product access, engineering, and production
Creative and innovative applications of cellular programming
Medical applications, tissue engineering, and the programming of therapeutic cells
Minimal cell design and construction
Genomics and genome replacement strategies
Viral engineering
Automated and robotic assembly platforms for synthetic biology
DNA synthesis methodologies
Metagenomics and synthetic metagenomic analysis
Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction
Gene optimization
Methods for genome-scale measurements of transcription and metabolomics
Systems biology and methods to integrate multiple data sources
in vitro and cell-free synthetic biology and molecular programming
Nucleic acid engineering.