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Engineering functional materials through bacteria-assisted living grafting. 通过细菌辅助活体接枝技术制造功能材料。
Cell systems Pub Date : 2024-03-20 Epub Date: 2024-03-08 DOI: 10.1016/j.cels.2024.02.003
Runtao Zhu, Jiao Zhang, Lin Wang, Yunfeng Zhang, Yang Zhao, Ying Han, Jing Sun, Xi Zhang, Ying Dou, Huaxiong Yao, Wei Yan, Xiaozhou Luo, Junbiao Dai, Zhuojun Dai
{"title":"Engineering functional materials through bacteria-assisted living grafting.","authors":"Runtao Zhu, Jiao Zhang, Lin Wang, Yunfeng Zhang, Yang Zhao, Ying Han, Jing Sun, Xi Zhang, Ying Dou, Huaxiong Yao, Wei Yan, Xiaozhou Luo, Junbiao Dai, Zhuojun Dai","doi":"10.1016/j.cels.2024.02.003","DOIUrl":"10.1016/j.cels.2024.02.003","url":null,"abstract":"<p><p>Functionalizing materials with biomacromolecules such as enzymes has broad applications in biotechnology and biomedicine. Here, we introduce a grafting method mediated by living cells to functionalize materials. We use polymeric scaffolds to trap engineered bacteria and micron-sized particles with chemical groups serving as active sites for grafting. The bacteria synthesize the desired protein for grafting and autonomously lyse to release it. The released functional moieties are locally grafted onto the active sites, generating the materials engineered by living grafting (MELGs). MELGs are resilient to perturbations because of both the bonding and the regeneration of functional domains synthesized by living cells. The programmability of the bacteria enables us to fabricate MELGs that can respond to external input, decompose a pollutant, reconstitute synthetic pathways for natural product synthesis, and purify mismatched DNA. Our work establishes a bacteria-assisted grafting strategy to functionalize materials with a broad range of biological activities in an integrated, flexible, and modular manner. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"264-274.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069014","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}
引用次数: 0
Sustainable protein regeneration in encapsulated materials. 封装材料中的可持续蛋白质再生。
Cell systems Pub Date : 2024-03-20 DOI: 10.1016/j.cels.2024.02.004
Sourik Dey, Shrikrishnan Sankaran
{"title":"Sustainable protein regeneration in encapsulated materials.","authors":"Sourik Dey, Shrikrishnan Sankaran","doi":"10.1016/j.cels.2024.02.004","DOIUrl":"10.1016/j.cels.2024.02.004","url":null,"abstract":"<p><p>Zhu et al. introduce MELG (materials engineered by living grafting), combining engineered microbes with non-living scaffolds for functional protein regeneration within. These MELGs can be used for long-term controlled release, enzyme-mediated biocatalysis, and DNA purification. This approach offers enhanced functionality and durability in bioactive materials compared to traditional non-living counterparts.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 3","pages":"211-212"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186609","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}
引用次数: 0
What can recent methodological advances help us understand about protein and genome evolution? 最新的方法论进展能帮助我们了解蛋白质和基因组进化的哪些方面?
Cell systems Pub Date : 2024-03-20 DOI: 10.1016/j.cels.2024.02.006
{"title":"What can recent methodological advances help us understand about protein and genome evolution?","authors":"","doi":"10.1016/j.cels.2024.02.006","DOIUrl":"10.1016/j.cels.2024.02.006","url":null,"abstract":"","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 3","pages":"205-210"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186610","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}
引用次数: 0
Widespread alteration of protein autoinhibition in human cancers. 人类癌症中蛋白质自身抑制的广泛改变。
Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-15 DOI: 10.1016/j.cels.2024.01.009
Jorge A Holguin-Cruz, Jennifer M Bui, Ashwani Jha, Dokyun Na, Jörg Gsponer
{"title":"Widespread alteration of protein autoinhibition in human cancers.","authors":"Jorge A Holguin-Cruz, Jennifer M Bui, Ashwani Jha, Dokyun Na, Jörg Gsponer","doi":"10.1016/j.cels.2024.01.009","DOIUrl":"10.1016/j.cels.2024.01.009","url":null,"abstract":"<p><p>Autoinhibition is a prevalent allosteric regulatory mechanism in signaling proteins. Reduced autoinhibition underlies the tumorigenic effect of some known cancer drivers, but whether autoinhibition is altered generally in cancer remains elusive. Here, we demonstrate that cancer-associated missense mutations, in-frame insertions/deletions, and fusion breakpoints are enriched within inhibitory allosteric switches (IASs) across all cancer types. Selection for IASs that are recurrently mutated in cancers identifies established and unknown cancer drivers. Recurrent missense mutations in IASs of these drivers are associated with distinct, cancer-specific changes in molecular signaling. For the specific case of PPP3CA, the catalytic subunit of calcineurin, we provide insights into the molecular mechanisms of altered autoinhibition by cancer mutations using biomolecular simulations, and demonstrate that such mutations are associated with transcriptome changes consistent with increased calcineurin signaling. Our integrative study shows that autoinhibition-modulating genetic alterations are positively selected for by cancer cells.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"246-263.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747962","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}
引用次数: 0
Clonal differences underlie variable responses to sequential and prolonged treatment. 克隆差异是对连续和长期治疗产生不同反应的原因。
Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-23 DOI: 10.1016/j.cels.2024.01.011
Dylan L Schaff, Aria J Fasse, Phoebe E White, Robert J Vander Velde, Sydney M Shaffer
{"title":"Clonal differences underlie variable responses to sequential and prolonged treatment.","authors":"Dylan L Schaff, Aria J Fasse, Phoebe E White, Robert J Vander Velde, Sydney M Shaffer","doi":"10.1016/j.cels.2024.01.011","DOIUrl":"10.1016/j.cels.2024.01.011","url":null,"abstract":"<p><p>Cancer cells exhibit dramatic differences in gene expression at the single-cell level, which can predict whether they become resistant to treatment. Treatment perpetuates this heterogeneity, resulting in a diversity of cell states among resistant clones. However, it remains unclear whether these differences lead to distinct responses when another treatment is applied or the same treatment is continued. In this study, we combined single-cell RNA sequencing with barcoding to track resistant clones through prolonged and sequential treatments. We found that cells within the same clone have similar gene expression states after multiple rounds of treatment. Moreover, we demonstrated that individual clones have distinct and differing fates, including growth, survival, or death, when subjected to a second treatment or when the first treatment is continued. By identifying gene expression states that predict clone survival, this work provides a foundation for selecting optimal therapies that target the most aggressive resistant clones within a tumor. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"213-226.e9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11003565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944788","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}
引用次数: 0
Convolutions are competitive with transformers for protein sequence pretraining. 在蛋白质序列预训练方面,卷积与变换器具有竞争性。
Cell systems Pub Date : 2024-03-20 Epub Date: 2024-02-29 DOI: 10.1016/j.cels.2024.01.008
Kevin K Yang, Nicolo Fusi, Alex X Lu
{"title":"Convolutions are competitive with transformers for protein sequence pretraining.","authors":"Kevin K Yang, Nicolo Fusi, Alex X Lu","doi":"10.1016/j.cels.2024.01.008","DOIUrl":"10.1016/j.cels.2024.01.008","url":null,"abstract":"<p><p>Pretrained protein sequence language models have been shown to improve the performance of many prediction tasks and are now routinely integrated into bioinformatics tools. However, these models largely rely on the transformer architecture, which scales quadratically with sequence length in both run-time and memory. Therefore, state-of-the-art models have limitations on sequence length. To address this limitation, we investigated whether convolutional neural network (CNN) architectures, which scale linearly with sequence length, could be as effective as transformers in protein language models. With masked language model pretraining, CNNs are competitive with, and occasionally superior to, transformers across downstream applications while maintaining strong performance on sequences longer than those allowed in the current state-of-the-art transformer models. Our work suggests that computational efficiency can be improved without sacrificing performance, simply by using a CNN architecture instead of a transformer, and emphasizes the importance of disentangling pretraining task and model architecture. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"286-294.e2"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013789","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}
引用次数: 0
Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells. 在罕见体细胞中回溯鉴定标志多能潜能的细胞内在因子。
Cell systems Pub Date : 2024-02-21 Epub Date: 2024-02-08 DOI: 10.1016/j.cels.2024.01.001
Naveen Jain, Yogesh Goyal, Margaret C Dunagin, Christopher J Cote, Ian A Mellis, Benjamin Emert, Connie L Jiang, Ian P Dardani, Sam Reffsin, Miles Arnett, Wenli Yang, Arjun Raj
{"title":"Retrospective identification of cell-intrinsic factors that mark pluripotency potential in rare somatic cells.","authors":"Naveen Jain, Yogesh Goyal, Margaret C Dunagin, Christopher J Cote, Ian A Mellis, Benjamin Emert, Connie L Jiang, Ian P Dardani, Sam Reffsin, Miles Arnett, Wenli Yang, Arjun Raj","doi":"10.1016/j.cels.2024.01.001","DOIUrl":"10.1016/j.cels.2024.01.001","url":null,"abstract":"<p><p>Pluripotency can be induced in somatic cells by the expression of OCT4, KLF4, SOX2, and MYC. Usually only a rare subset of cells reprogram, and the molecular characteristics of this subset remain unknown. We apply retrospective clone tracing to identify and characterize the rare human fibroblasts primed for reprogramming. These fibroblasts showed markers of increased cell cycle speed and decreased fibroblast activation. Knockdown of a fibroblast activation factor identified by our analysis increased the reprogramming efficiency. We provide evidence for a unified model in which cells can move into and out of the primed state over time, explaining how reprogramming appears deterministic at short timescales and stochastic at long timescales. Furthermore, inhibiting the activity of LSD1 enlarged the pool of cells that were primed for reprogramming. Thus, even homogeneous cell populations can exhibit heritable molecular variability that can dictate whether individual rare cells will reprogram or not.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"109-133.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10940218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713514","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}
引用次数: 0
Mapping combinatorial expression perturbations to growth in Escherichia coli. 绘制组合表达扰动与大肠杆菌生长的关系图。
Cell systems Pub Date : 2024-02-21 DOI: 10.1016/j.cels.2024.01.006
J Scott P McCain
{"title":"Mapping combinatorial expression perturbations to growth in Escherichia coli.","authors":"J Scott P McCain","doi":"10.1016/j.cels.2024.01.006","DOIUrl":"10.1016/j.cels.2024.01.006","url":null,"abstract":"<p><p>The connection between growth and gene expression has often been considered in a single gene. Repurposing a drug-drug interaction model, the multidimensional effects of several simultaneous gene expression perturbations on growth have been examined in the model bacteria Escherichia coli.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 2","pages":"106-108"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934737","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}
引用次数: 0
A top variant identification pipeline for protein engineering. 用于蛋白质工程的顶级变异识别管道。
Cell systems Pub Date : 2024-02-21 DOI: 10.1016/j.cels.2024.01.010
Hui Chen, Zhike Lu, Lijia Ma
{"title":"A top variant identification pipeline for protein engineering.","authors":"Hui Chen, Zhike Lu, Lijia Ma","doi":"10.1016/j.cels.2024.01.010","DOIUrl":"10.1016/j.cels.2024.01.010","url":null,"abstract":"<p><p>Understanding the fitness of protein variants with combinatorial mutations is critical for effective protein engineering. In this issue of Cell Systems, Chu et al. present TopVIP, a top variant identification pipeline that enables accurate picking of the greatest number of best-performing protein variants with high-fitness leveraging zero-shot predictor and low-N iterative sampling.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 2","pages":"105-106"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934706","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}
引用次数: 0
Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter. 利用基于相分离的荧光报告器实现亚显微蛋白质团簇的简单可视化。
Cell systems Pub Date : 2024-02-21 Epub Date: 2024-02-08 DOI: 10.1016/j.cels.2024.01.005
Thomas R Mumford, Diarmid Rae, Emily Brackhahn, Abbas Idris, David Gonzalez-Martinez, Ayush Aditya Pal, Michael C Chung, Juan Guan, Elizabeth Rhoades, Lukasz J Bugaj
{"title":"Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter.","authors":"Thomas R Mumford, Diarmid Rae, Emily Brackhahn, Abbas Idris, David Gonzalez-Martinez, Ayush Aditya Pal, Michael C Chung, Juan Guan, Elizabeth Rhoades, Lukasz J Bugaj","doi":"10.1016/j.cels.2024.01.005","DOIUrl":"10.1016/j.cels.2024.01.005","url":null,"abstract":"<p><p>Protein clustering plays numerous roles in cell physiology and disease. However, protein oligomers can be difficult to detect because they are often too small to appear as puncta in conventional fluorescence microscopy. Here, we describe a fluorescent reporter strategy that detects protein clusters with high sensitivity called CluMPS (clusters magnified by phase separation). A CluMPS reporter detects and visually amplifies even small clusters of a binding partner, generating large, quantifiable fluorescence condensates. We use computational modeling and optogenetic clustering to demonstrate that CluMPS can detect small oligomers and behaves rationally according to key system parameters. CluMPS detected small aggregates of pathological proteins where the corresponding GFP fusions appeared diffuse. CluMPS also detected and tracked clusters of unmodified and tagged endogenous proteins, and orthogonal CluMPS probes could be multiplexed in cells. CluMPS provides a powerful yet straightforward approach to observe higher-order protein assembly in its native cellular context. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"166-179.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713515","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}
引用次数: 0
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