Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner
{"title":"The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease","authors":"Roger A. Barker, Nicholas P. Lao-Kaim, Natalie Valle Guzman, Dilan Athauda, Hjalmar Bjartmarz, Anders Björklund, Alistair Church, Emma Cutting, Danielle Daft, Viswas Dayal, Stephen Dunnett, Amy Evans, Shane Grealish, Naomi Hannaway, Xiaoling He, Sam Hewitt, Zinovia Kefalopoulou, Philipp Mahlknecht, Antonio Martín-Bastida, Krista Farrell, Sarah Moore, Harry Bulstrode, Tagore Nakornchai, Jenny Nelander-Wahlestedt, Linnea Roupé, Gesine Paul, Kathryn Peall, Anne Rosser, Adriana Roca-Fernández, Sophie Rowlands, Anne-Marie McGorrian, Caroline Scherf, Ngoc Nga Vinh, Victoria Roberton, Claire Kelly, Mariah Lelos, Eduardo Torres, Kate Shires, Rachel Hills, Debbie Williams, Andreas-Antonios Roussakis, Krista Sibley, Pamela Tyers, Ruwani Wijeyekoon, Caroline Williams-Gray, Thomas Foltynie, Paola Piccini, Robert Morris, Stanley E. Lazic, Olle Lindvall, Malin Parmar, Hakan Widner","doi":"10.1038/s41587-025-02567-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02567-2","url":null,"abstract":"<p>Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson’s disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial (NCT01898390) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation protocol but different implantation devices. No overall clinical effect was seen for the primary endpoint 3 years after grafting. No major graft-induced dyskinesias were seen, but we observed differences in outcome related to transplant device and/or site. Mean dopamine uptake improved at 18 months in seven individuals according to [<sup>18</sup>F]fluorodopa positron emission tomography imaging but was restored to near-normal levels in only one individual. Our findings highlight the need for a stem cell source of dopamine neurons for potential Parkinson’s disease cell therapy and provide critical insights into how such clinical studies should be approached.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"138 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diederik S. Laman Trip, Marc van Oostrum, Danish Memon, Fabian Frommelt, Delora Baptista, Kalpana Panneerselvam, Glyn Bradley, Luana Licata, Henning Hermjakob, Sandra Orchard, Gosia Trynka, Ellen M. McDonagh, Andrea Fossati, Ruedi Aebersold, Matthias Gstaiger, Bernd Wollscheid, Pedro Beltrao
{"title":"A tissue-specific atlas of protein–protein associations enables prioritization of candidate disease genes","authors":"Diederik S. Laman Trip, Marc van Oostrum, Danish Memon, Fabian Frommelt, Delora Baptista, Kalpana Panneerselvam, Glyn Bradley, Luana Licata, Henning Hermjakob, Sandra Orchard, Gosia Trynka, Ellen M. McDonagh, Andrea Fossati, Ruedi Aebersold, Matthias Gstaiger, Bernd Wollscheid, Pedro Beltrao","doi":"10.1038/s41587-025-02659-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02659-z","url":null,"abstract":"<p>Despite progress in mapping protein–protein interactions, their tissue specificity is understudied. Here, given that protein coabundance is predictive of functional association, we compiled and analyzed protein abundance data of 7,811 proteomic samples from 11 human tissues to produce an atlas of tissue-specific protein associations. We find that this method recapitulates known protein complexes and the larger structural organization of the cell. Interactions of stable protein complexes are well preserved across tissues, while cell-type-specific cellular structures, such as synaptic components, are found to represent a substantial driver of differences between tissues. Over 25% of associations are tissue specific, of which <7% are because of differences in gene expression. We validate protein associations for the brain through cofractionation experiments in synaptosomes, curation of brain-derived pulldown data and AlphaFold2 modeling. We also construct a network of brain interactions for schizophrenia-related genes, indicating that our approach can functionally prioritize candidate disease genes in loci linked to brain disorders.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"111 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Clavel, Franziska Faber, Mathieu Groussin, Dirk Haller, Jörg Overmann, Charlie Pauvert, Mathilde Poyet, Joel Selkrig, Bärbel Stecher, Athanasios Typas, Maria J. G. T. Vehreschild, Alexander J. Westermann, David Wylensek, Lisa Maier
{"title":"Enabling next-generation anaerobic cultivation through biotechnology to advance functional microbiome research","authors":"Thomas Clavel, Franziska Faber, Mathieu Groussin, Dirk Haller, Jörg Overmann, Charlie Pauvert, Mathilde Poyet, Joel Selkrig, Bärbel Stecher, Athanasios Typas, Maria J. G. T. Vehreschild, Alexander J. Westermann, David Wylensek, Lisa Maier","doi":"10.1038/s41587-025-02660-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02660-6","url":null,"abstract":"<p>Microbiomes are complex communities of microorganisms that are essential for biochemical processes on Earth and for the health of humans, animals and plants. Many environmental and host-associated microbiomes are dominated by anaerobic microbes, some of which cannot tolerate oxygen. Anaerobic microbial communities have been extensively studied over the last 20 years using molecular techniques, especially next-generation sequencing. However, there is a renewed interest in microbial cultivation because isolates provide the basis for understanding the taxonomic and functional units of biodiversity, elucidating novel biochemical pathways and the mechanisms underlying microbe–microbe and microbe–host interactions and opening new avenues for biotechnological and clinical applications. In this Perspective, we present areas of research and applications that will benefit from advancement in anaerobic microbial cultivation. We highlight key technical and infrastructural hurdles associated with the development and deployment of sophisticated cultivation workflows. Improving the performance of cultivation techniques will set new trends in functional microbiome research in the coming years.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"222 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cara A. Griffiths, Xiaochao Xue, Javier A. Miret, Fernando Salvagiotti, Liana G. Acevedo-Siaca, Jacinta Gimeno, Matthew P. Reynolds, Kirsty L. Hassall, Kirstie Halsey, Swati Puranik, Maria Oszvald, Smita Kurup, Benjamin G. Davis, Matthew J. Paul
{"title":"Membrane-permeable trehalose 6-phosphate precursor spray increases wheat yields in field trials","authors":"Cara A. Griffiths, Xiaochao Xue, Javier A. Miret, Fernando Salvagiotti, Liana G. Acevedo-Siaca, Jacinta Gimeno, Matthew P. Reynolds, Kirsty L. Hassall, Kirstie Halsey, Swati Puranik, Maria Oszvald, Smita Kurup, Benjamin G. Davis, Matthew J. Paul","doi":"10.1038/s41587-025-02611-1","DOIUrl":"https://doi.org/10.1038/s41587-025-02611-1","url":null,"abstract":"<p>Trehalose 6-phosphate (T6P) is an endogenous sugar signal in plants that promotes growth, yet it cannot be introduced directly into crops or fully genetically controlled. Here we show that wheat yields were improved using a timed microdose of a plant-permeable, sunlight-activated T6P signaling precursor, DMNB-T6P, under a variety of agricultural conditions. Under both well-watered and water-stressed conditions over 4 years, DMNB-T6P stimulated yield of three elite varieties. Yield increases were an order of magnitude larger than average annual genetic gains of breeding programs and occurred without additional water or fertilizer. Mechanistic analyses reveal that these benefits arise from increased CO<sub>2</sub> fixation and linear electron flow (‘source’) as well as from increased starchy endosperm volume, enhanced grain sieve tube development and upregulation of genes for starch, amino acid and protein synthesis (‘sink’). These data demonstrate a step-change, scalable technology with net benefit to the environment that could provide sustainable yield improvements of diverse staple cereal crops.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"66 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Environmental monitoring from the air with hyperspectral reporters","authors":"Maxwell Z. Wilson","doi":"10.1038/s41587-025-02668-y","DOIUrl":"https://doi.org/10.1038/s41587-025-02668-y","url":null,"abstract":"Hyperspectral reporters allow bacteria on the ground to be imaged by high-flying drones, expanding environmental monitoring to large outdoor areas.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"82 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of a sunlight-switched sugar signal increases wheat yield in the field","authors":"","doi":"10.1038/s41587-025-02667-z","DOIUrl":"https://doi.org/10.1038/s41587-025-02667-z","url":null,"abstract":"Crop yield improvement has plateaued in the past three decades, owing largely to genetic bottlenecks in the germplasm of staple food crops. We used a chemical intervention method that increases yield in the field, providing a sustainable means to improve yields of wheat and potentially other crops.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"18 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Precision neuroscience","authors":"","doi":"10.1038/s41587-025-02673-1","DOIUrl":"https://doi.org/10.1038/s41587-025-02673-1","url":null,"abstract":"Developers are recombining or sharpening established drugs, molecules and mechanisms to create a new generation of neurology therapies.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"27 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemigenetic kinase biosensors illuminate cell signaling networks","authors":"Katarina Nemec, Vikas D. Trivedi, M. Madan Babu","doi":"10.1038/s41587-025-02672-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02672-2","url":null,"abstract":"Red-shifted chemigenetic biosensors enable sensitive, multiplexed detection of intracellular signaling in living cells across various subcellular compartments and microscopy setups.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"7 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengdi Wang, Zaixi Zhang, Amrit Singh Bedi, Alvaro Velasquez, Stephanie Guerra, Sheng Lin-Gibson, Le Cong, Yuanhao Qu, Souradip Chakraborty, Megan Blewett, Jian Ma, Eric Xing, George Church
{"title":"A call for built-in biosecurity safeguards for generative AI tools","authors":"Mengdi Wang, Zaixi Zhang, Amrit Singh Bedi, Alvaro Velasquez, Stephanie Guerra, Sheng Lin-Gibson, Le Cong, Yuanhao Qu, Souradip Chakraborty, Megan Blewett, Jian Ma, Eric Xing, George Church","doi":"10.1038/s41587-025-02650-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02650-8","url":null,"abstract":"<p>Generative AI is changing biotechnology research, and accelerating drug discovery, protein design and synthetic biology. It also enhances biomedical imaging, personalized medicine and laboratory automation, which enables faster and more efficient scientific advancements. However, these breakthroughs have also raised biosecurity concerns, which has prompted policy and community discussions<sup>1,2,3,4</sup>.</p><p>The power of generative AI lies in its ability to generalize from known data to the unknown. Deep generative models can predict novel biological molecules that might not resemble existing genome sequences or proteins. This capability introduces dual-use risks and serious biosecurity threats — such models could potentially bypass the established safety screening mechanisms used by nucleic acid synthesis providers<sup>5</sup>, which presently rely on database matching to identify sequences of concerns<sup>6</sup>. AI-driven tools could be misused to engineer pathogens, toxins or destabilizing biomolecules, and AI science agents could amplify risks by automating experimental designs<sup>7</sup>.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"1 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Agnostic viral detection at single-cell resolution reveals novel viruses","authors":"","doi":"10.1038/s41587-025-02638-4","DOIUrl":"https://doi.org/10.1038/s41587-025-02638-4","url":null,"abstract":"We introduce a method that detects viral sequences in RNA sequencing data on the basis of highly conserved proteins, enabling the detection of more than 100,000 RNA virus species. We analyzed the presence of novel viruses and host gene expression in parallel to characterize viral tropism and host immune responses in individual cells.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"35 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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