Jai P. Padmakumar, Jessica J. Sun, William Cho, Yangruirui Zhou, Christopher Krenz, Woo Zhong Han, Douglas Densmore, Eduardo D. Sontag, Christopher A. Voigt
{"title":"Partitioning of a 2-bit hash function across 66 communicating cells","authors":"Jai P. Padmakumar, Jessica J. Sun, William Cho, Yangruirui Zhou, Christopher Krenz, Woo Zhong Han, Douglas Densmore, Eduardo D. Sontag, Christopher A. Voigt","doi":"10.1038/s41589-024-01730-1","DOIUrl":null,"url":null,"abstract":"<p>Powerful distributed computing can be achieved by communicating cells that individually perform simple operations. Here, we report design software to divide a large genetic circuit across cells as well as the genetic parts to implement the subcircuits in their genomes. These tools were demonstrated using a 2-bit version of the MD5 hashing algorithm, which is an early predecessor to the cryptographic functions underlying cryptocurrency. One iteration requires 110 logic gates, which were partitioned across 66 <i>Escherichia coli</i> strains, requiring the introduction of a total of 1.1 Mb of recombinant DNA into their genomes. The strains were individually experimentally verified to integrate their assigned input signals, process this information correctly and propagate the result to the cell in the next layer. This work demonstrates the potential to obtain programable control of multicellular biological processes.</p><figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"35 1","pages":""},"PeriodicalIF":12.9000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature chemical biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41589-024-01730-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Powerful distributed computing can be achieved by communicating cells that individually perform simple operations. Here, we report design software to divide a large genetic circuit across cells as well as the genetic parts to implement the subcircuits in their genomes. These tools were demonstrated using a 2-bit version of the MD5 hashing algorithm, which is an early predecessor to the cryptographic functions underlying cryptocurrency. One iteration requires 110 logic gates, which were partitioned across 66 Escherichia coli strains, requiring the introduction of a total of 1.1 Mb of recombinant DNA into their genomes. The strains were individually experimentally verified to integrate their assigned input signals, process this information correctly and propagate the result to the cell in the next layer. This work demonstrates the potential to obtain programable control of multicellular biological processes.
期刊介绍:
Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision.
The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms.
Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.