Cell systemsPub Date : 2024-11-20Epub Date: 2024-11-13DOI: 10.1016/j.cels.2024.10.008
Claire Sayers, Vikash Pandey, Arjun Balakrishnan, Katharine Michie, Dennis Svedberg, Mirjam Hunziker, Mercedes Pardo, Jyoti Choudhary, Ronnie Berntsson, Oliver Billker
{"title":"Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote.","authors":"Claire Sayers, Vikash Pandey, Arjun Balakrishnan, Katharine Michie, Dennis Svedberg, Mirjam Hunziker, Mercedes Pardo, Jyoti Choudhary, Ronnie Berntsson, Oliver Billker","doi":"10.1016/j.cels.2024.10.008","DOIUrl":"10.1016/j.cels.2024.10.008","url":null,"abstract":"<p><p>Sexual reproduction in malaria parasites is essential for their transmission to mosquitoes and offers a divergent eukaryote model to understand the evolution of sex. Through a panel of genetic screens in Plasmodium berghei, we identify 348 sex and transmission-related genes and define roles for unstudied genes as putative targets for transmission-blocking interventions. The functional data provide a deeper understanding of female metabolic reprogramming, meiosis, and the axoneme. We identify a complex of a SUN domain protein (SUN1) and a putative allantoicase (ALLC1) that is essential for male fertility by linking the microtubule organizing center to the nuclear envelope and enabling mitotic spindle formation during male gametogenesis. Both proteins have orthologs in mouse testis, and the data raise the possibility of an ancient role for atypical SUN domain proteins in coupling the nucleus and axoneme. Altogether, our data provide an unbiased picture of the molecular processes that underpin malaria parasite transmission. 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":"1075-1091.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634561","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}
Cell systemsPub Date : 2024-11-20DOI: 10.1016/j.cels.2024.10.003
Divya Choudhary, Kevin R Foster, Stephan Uphoff
{"title":"The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time.","authors":"Divya Choudhary, Kevin R Foster, Stephan Uphoff","doi":"10.1016/j.cels.2024.10.003","DOIUrl":"10.1016/j.cels.2024.10.003","url":null,"abstract":"<p><p>Bacteria employ diverse gene regulatory networks to survive stress, but deciphering the underlying logic of these complex networks has proved challenging. Here, we use time-resolved single-cell imaging to explore the functioning of the E. coli regulatory response to oxidative stress. We observe diverse gene expression dynamics within the network. However, by controlling for stress-induced growth-rate changes, we show that these patterns involve just three classes of regulation: downregulated genes, upregulated pulsatile genes, and gradually upregulated genes. The two upregulated classes are distinguished by differences in the binding of the transcription factor, OxyR, and appear to play distinct roles during stress protection. Pulsatile genes activate transiently in a few cells for initial protection of a group of cells, whereas gradually upregulated genes induce evenly, generating a lasting protection involving many cells. Our study shows how bacterial populations use simple regulatory principles to coordinate stress responses in space and time. 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":"1033-1045.e6"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634564","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}
Cell systemsPub Date : 2024-11-20DOI: 10.1016/j.cels.2024.10.010
Shruthi Viswanath
{"title":"AlphaFold opens the doors to deorphanizing secreted proteins.","authors":"Shruthi Viswanath","doi":"10.1016/j.cels.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.cels.2024.10.010","url":null,"abstract":"<p><p>Danneskiold-Samsøe and coworkers<sup>1</sup> have developed an in silico screening pipeline based on AlphaFold2 for identifying single-pass transmembrane receptors for secreted peptides that play important roles in cell-cell signaling. Their approach can be used to deorphanize a diverse range of ligands. The overall strategy can be valuable in screening for weak and transient interactions.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 11","pages":"1000-1001"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690106","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}
Cell systemsPub Date : 2024-11-20Epub Date: 2024-11-07DOI: 10.1016/j.cels.2024.10.009
Anna Weiss, Matti Gralka, Karoline Faust, David Basanta Gutierrez, Kenneth Pienta, Xu Zhou, Ophelia S Venturelli, Sean Gibbons, Mo Ebrahimkhani, Nika Shakiba, Shaohua Ma
{"title":"How can concepts from ecology enable insights about cellular communities?","authors":"Anna Weiss, Matti Gralka, Karoline Faust, David Basanta Gutierrez, Kenneth Pienta, Xu Zhou, Ophelia S Venturelli, Sean Gibbons, Mo Ebrahimkhani, Nika Shakiba, Shaohua Ma","doi":"10.1016/j.cels.2024.10.009","DOIUrl":"10.1016/j.cels.2024.10.009","url":null,"abstract":"","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1103"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607702","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}
Cell systemsPub Date : 2024-11-20Epub Date: 2024-11-13DOI: 10.1016/j.cels.2024.10.004
Niels Banhos Danneskiold-Samsøe, Deniz Kavi, Kevin M Jude, Silas Boye Nissen, Lianna W Wat, Laetitia Coassolo, Meng Zhao, Galia Asae Santana-Oikawa, Beatrice Blythe Broido, K Christopher Garcia, Katrin J Svensson
{"title":"AlphaFold2 enables accurate deorphanization of ligands to single-pass receptors.","authors":"Niels Banhos Danneskiold-Samsøe, Deniz Kavi, Kevin M Jude, Silas Boye Nissen, Lianna W Wat, Laetitia Coassolo, Meng Zhao, Galia Asae Santana-Oikawa, Beatrice Blythe Broido, K Christopher Garcia, Katrin J Svensson","doi":"10.1016/j.cels.2024.10.004","DOIUrl":"10.1016/j.cels.2024.10.004","url":null,"abstract":"<p><p>Secreted proteins play crucial roles in paracrine and endocrine signaling; however, identifying ligand-receptor interactions remains challenging. Here, we benchmarked AlphaFold2 (AF2) as a screening approach to identify extracellular ligands to single-pass transmembrane receptors. Key to the approach is the optimization of AF2 input and output for screening ligands against receptors to predict the most probable ligand-receptor interactions. The predictions were performed on ligand-receptor pairs not used for AF2 training. We demonstrate high discriminatory power and a success rate of close to 90% for known ligand-receptor pairs and 50% for a diverse set of experimentally validated interactions. Further, we show that screen accuracy does not correlate linearly with prediction of ligand-receptor interaction. These results demonstrate a proof of concept of a rapid and accurate screening platform to predict high-confidence cell-surface receptors for a diverse set of ligands by structural binding prediction, with potentially wide applicability for the understanding of cell-cell communication.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"1046-1060.e3"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634554","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}
Cell systemsPub Date : 2024-11-20Epub Date: 2024-11-13DOI: 10.1016/j.cels.2024.10.007
Guillaume Urtecho, Thomas Moody, Yiming Huang, Ravi U Sheth, Miles Richardson, Hélène C Descamps, Andrew Kaufman, Opeyemi Lekan, Zetian Zhang, Florencia Velez-Cortes, Yiming Qu, Lucas Cohen, Deirdre Ricaurte, Travis E Gibson, Georg K Gerber, Christoph A Thaiss, Harris H Wang
{"title":"Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.","authors":"Guillaume Urtecho, Thomas Moody, Yiming Huang, Ravi U Sheth, Miles Richardson, Hélène C Descamps, Andrew Kaufman, Opeyemi Lekan, Zetian Zhang, Florencia Velez-Cortes, Yiming Qu, Lucas Cohen, Deirdre Ricaurte, Travis E Gibson, Georg K Gerber, Christoph A Thaiss, Harris H Wang","doi":"10.1016/j.cels.2024.10.007","DOIUrl":"10.1016/j.cels.2024.10.007","url":null,"abstract":"<p><p>While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural \"super-donor\" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent 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":"1002-1017.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634556","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}
Cell systemsPub Date : 2024-11-20DOI: 10.1016/j.cels.2024.10.011
Razan N Alnahhas, Mary J Dunlop
{"title":"Evaluation of Choudhary et al.: Single-cell gene expression dynamics in the E. coli oxidative stress response network.","authors":"Razan N Alnahhas, Mary J Dunlop","doi":"10.1016/j.cels.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.cels.2024.10.011","url":null,"abstract":"<p><p>One snapshot of the peer review process for \"The master regulator OxyR orchestrates bacterial oxidative stress response genes in space and time\" (Choudhary et al., 2024).<sup>1</sup>.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 11","pages":"991-993"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690110","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}
Cell systemsPub Date : 2024-11-20DOI: 10.1016/j.cels.2024.10.012
Derek N Woolfson, Lucy J Colwell, Zibo Chen, Anastassia A Vorobieva, Nicholas F Polizzi, Amelie Stein, Haiyan Liu, Fabio Parmeggiani, Anna Peacock, Rohit Singh, Neil King, Marinka Zitnik, Roberto A Chica
{"title":"How do you anticipate computational protein design will change biotechnology and therapeutic development?","authors":"Derek N Woolfson, Lucy J Colwell, Zibo Chen, Anastassia A Vorobieva, Nicholas F Polizzi, Amelie Stein, Haiyan Liu, Fabio Parmeggiani, Anna Peacock, Rohit Singh, Neil King, Marinka Zitnik, Roberto A Chica","doi":"10.1016/j.cels.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.cels.2024.10.012","url":null,"abstract":"","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 11","pages":"994-999"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690114","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}
Cell systemsPub Date : 2024-11-20Epub Date: 2024-11-05DOI: 10.1016/j.cels.2024.10.002
Feng-Shu Hsieh, Duy P M Nguyen, Mathias S Heltberg, Chia-Chou Wu, Yi-Chen Lee, Mogens H Jensen, Sheng-Hong Chen
{"title":"Plausible, robust biological oscillations through allelic buffering.","authors":"Feng-Shu Hsieh, Duy P M Nguyen, Mathias S Heltberg, Chia-Chou Wu, Yi-Chen Lee, Mogens H Jensen, Sheng-Hong Chen","doi":"10.1016/j.cels.2024.10.002","DOIUrl":"10.1016/j.cels.2024.10.002","url":null,"abstract":"<p><p>Biological oscillators can specify time- and dose-dependent functions via dedicated control of their oscillatory dynamics. However, how biological oscillators, which recurrently activate noisy biochemical processes, achieve robust oscillations remains unclear. Here, we characterize the long-term oscillations of p53 and its negative feedback regulator Mdm2 in single cells after DNA damage. Whereas p53 oscillates regularly, Mdm2 from a single MDM2 allele exhibits random unresponsiveness to ∼9% of p53 pulses. Using allelic-specific imaging of MDM2 activity, we show that MDM2 alleles buffer each other to maintain p53 pulse amplitude. Removal of MDM2 allelic buffering cripples the robustness of p53 amplitude, thereby elevating p21 levels and cell-cycle arrest. In silico simulations support that allelic buffering enhances the robustness of biological oscillators and broadens their plausible biochemical space. Our findings show how allelic buffering ensures robust p53 oscillations, highlighting the potential importance of allelic buffering for the emergence of robust biological oscillators during evolution. 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":"1018-1032.e12"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592419","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}
Cell systemsPub Date : 2024-10-16DOI: 10.1016/j.cels.2024.09.009
Mengzhou Hu, Trey Ideker
{"title":"Putting proteins in context.","authors":"Mengzhou Hu, Trey Ideker","doi":"10.1016/j.cels.2024.09.009","DOIUrl":"https://doi.org/10.1016/j.cels.2024.09.009","url":null,"abstract":"<p><p>Proteins exhibit cell-type-specific functions and interactions, yet most ways of representing proteins lack any biological or environmental context. To address this gap, recent work by Li et al.<sup>1</sup> introduces PINNACLE, a geometric deep learning approach that generates contextualized representations of proteins by combined analysis of protein interactions and multiorgan single-cell transcriptomics.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"15 10","pages":"891-892"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142483085","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}