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通过工程菌对多细胞生物的基因表达进行编程,以调节生理机能。

Programming gene expression in multicellular organisms for physiology modulation through engineered bacteria.

机构信息

Department of Chemical Engineering, Texas A&M University, College Station, TX, USA.

出版信息

Nat Commun. 2021 May 11;12(1):2689. doi: 10.1038/s41467-021-22894-7.

Abstract

A central goal of synthetic biology is to predictably and efficiently reprogram living systems to perform computations and carry out specific biological tasks. Although there have been many advances in the bio-computational design of living systems, these advances have mainly been applied to microorganisms or cell lines; programming animal physiology remains challenging for synthetic biology because of the system complexity. Here, we present a bacteria-animal symbiont system in which engineered bacteria recognize external signals and modulate animal gene expression, twitching phenotype, and fat metabolism through RNA interference toward gfp, sbp-1, and unc-22 gene in C. elegans. By using genetic circuits in bacteria to control these RNA expressions, we are able to program the physiology of the model animal Caenorhabditis elegans with logic gates. We anticipate that engineered bacteria can be used more extensively to program animal physiology for agricultural, therapeutic, and basic science applications.

摘要

合成生物学的一个核心目标是可预测且有效地对生命系统进行重新编程,以执行计算和完成特定的生物学任务。尽管在生命系统的生物计算设计方面已经取得了许多进展,但这些进展主要应用于微生物或细胞系;由于系统的复杂性,对动物生理学进行编程仍然是合成生物学的一个挑战。在这里,我们提出了一个细菌-动物共生系统,其中经过工程改造的细菌可以识别外部信号,并通过 RNA 干扰调节秀丽隐杆线虫中的 GFP、sbp-1 和 unc-22 基因,从而调节动物的基因表达、抽搐表型和脂肪代谢。通过在细菌中使用遗传电路来控制这些 RNA 的表达,我们能够使用逻辑门对秀丽隐杆线虫这一模式动物的生理学进行编程。我们预计,经过工程改造的细菌可以更广泛地用于对动物生理学进行编程,以应用于农业、治疗和基础科学领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/491f/8113242/ab64acdd1520/41467_2021_22894_Fig1_HTML.jpg

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