
Ned Wingreen
Focus
Biological modeling; intracellular networks; molecular biophysics
Research
Intracellular networks in bacteria
Bacteria are constantly sensing their environments and adjusting their behavior accordingly. Signaling occurs through networks of proteins and nucleic acids, culminating in changes of gene expression and so changes in the proteome of the cell. We are focused on the architecture of these intracellular networks. What is the relation between network architecture and function? For example, can we understand the selection of architectures in terms of general information-processing concepts such as signal to noise, memory, and adaptation? Even in a single bacterium such as E. coli, there are hundreds of coexisting networks. Our belief is that a deep study of a small number of "model" networks will yield general tools to analyze information processing by cell. It is important to choose these model networks carefully. The network components should be well-characterized and the physiological function of the network should be known and subject to quantitative measurement. Probes of the internal dynamics of the network such as fluorescence resonance energy transfer (FRET) or direct imaging of dynamic spatial structure, will be critical in developing and testing quantitative models. It is also important to choose networks which complement each other well, spanning a broad range of architectures and functions. Over the years, the group has studied (i) quorum sensing, in which the cell slowly integrates signals from its neighbors to commit to a developmental decision such as invasion of a host, (ii) chemotaxis, which requires adaptation and rapid response to changing chemical concentrations, (iii) cell-division networks, where accuracy and checkpoints are essential, and (iv) metabolic networks which tie together diverse inputs to maintain homeostasis. These studies have greatly benefited from our long-term collaborations with the Bassler, Gitai, and Rabinowitz labs at Princeton.
Microbial communities
Biofilms, surface-attached communities of bacteria encased in an extracellular matrix, are a major mode of bacterial life. We collaborate with the Bassler and Stone labs at Princeton to study many aspects of biofilms, from their formation and maturation to their eventual disassembly, mostly using Vibrio cholerae as a model organism. The detailed experimental observations on biofilms call for biophysical modeling, and to this end we have developed both agent-based and a continuum models that capture the distinct stages of the biofilm lifecycle. We also collaborate with the Shaevitz lab in studies of activity-driven pattern formation by the bacterium Myxococcus xanthus, which aggregates and forms fruiting bodies in response to starvation. Finally, we are broadly interested in microbial diversity – why are there so many different species in essentially ever microbiota? We collaborate with the Donia lab to better understand the ecology of microbes in nature.
Intracellular phase separation
Biologists have recently come to appreciate that eukaryotic cells are home to a multiplicity of non-membrane bound compartments, many of which form and dissolve as needed for the cell to function. The data are accumulating that these dynamical biomolecular condensates enable many central cellular functions – from ribosome assembly, to DNA repair, to cell-fate determination – and understanding them will be the key to unlocking some of the most recalcitrant problems in cell biology. It seems clear that these compartments represent a type of separated phase, but there are many open questions concerning their formation, how specific biological components are included or excluded, and how these structures influence physiological and biochemical processes. In these studies, we collaborate closely with the Brangwynne and Jonikas labs at Princeton.
Biography
Ned Wingreen is the Howard A. Prior Professor of the Life Sciences at Princeton University. He is a member of the Department of Molecular Biology and of the Lewis-Sigler Institute for Integrative Genomics, where he is Director of Graduate Studies of the QCB Graduate Program. He is also Associate Director of the Princeton Center for Theoretical Science, and associated faculty in the Department of Physics. Ned received his Ph.D. in theoretical condensed matter physics from Cornell University in 1989. He did his postdoc in mesoscopic physics at MIT before moving, in 1991, to the NEC Research Institute in Princeton. At NEC, he continued to work in mesoscopic physics, but also started research in biophysics which grew into a general interest in problems at the interface of physics and biology. Ned joined Princeton University in 2004. Ned's current research focuses on modeling intracellular networks in bacteria and other microorganisms, as well as studies of microbial communities, and intracellular phase separation. He is a fellow of the American Physical Society and the American Association for the Advancement of Science.
Honors & Awards
2019
- President's Award for Distinguished Teaching, Princeton University
2012
- Elected Fellow of the AAAS, American Association for the Advancement of Science
2001
- Elected Fellow of the APS, American Physical Society
Education
- B.S., Physics, California Institute of Technology
- M.S., Ph.D., Physics, Cornell University
Selected Publications
- 1.Bridges A, Prentice J, Wingreen N, Bassler B. Signal Transduction Network Principles Underlying Bacterial Collective Behaviors. Annu Rev Microbiol. 2022;76:235–257. PMCID: PMC9463083
- 1.Ellison C, Fei C, Dalia T, Wingreen N, Dalia A, Shaevitz J, Gitai Z. Subcellular localization of type IV pili regulates bacterial multicellular development. Nat Commun. 2022;13(1):6334. PMCID: PMC9596432
- 1.Martínez-Calvo A, Bhattacharjee T, Bay K, Luu H, Hancock A, Wingreen N, Datta S. Morphological instability and roughening of growing 3D bacterial colonies. Proc Natl Acad Sci U S A. 2022;119(43):e2208019119. PMCID: PMC9618147
- 1.Landajuela A, Braun M, Martínez-Calvo A, Rodrigues C, Perez C, Doan T, Rudner D, Wingreen N, Karatekin E. Membrane fission during bacterial spore development requires cellular inflation driven by DNA translocation. Curr Biol. 2022;32(19):4186–4200.e8. PMCID: PMC9730832
- 1.Zhang D, Li S, King C, Wingreen N, Gitai Z, Li Z. Global and gene-specific translational regulation in Escherichia coli across different conditions. PLoS Comput Biol. 2022;18(10):e1010641. PMCID: PMC9624429
- 1.Fei C, Wilson A, Mangan N, Wingreen N, Jonikas M. Modelling the pyrenoid-based CO-concentrating mechanism provides insights into its operating principles and a roadmap for its engineering into crops. Nat Plants. 2022;8(5):583–595. PMCID: PMC9122830
- 1.Bridges A, Prentice J, Fei C, Wingreen N, Bassler B. Quantitative input-output dynamics of a c-di-GMP signal transduction cascade in Vibrio cholerae. PLoS Biol. 2022;20(3):e3001585. PMCID: PMC8967002
- 1.Ronceray P, Zhang Y, Liu X, Wingreen N. Stoichiometry Controls the Dynamics of Liquid Condensates of Associative Proteins. Phys Rev Lett. 2022;128(3):038102. PMID: 35119898
- 1.McEnany J, Meir Y, Wingreen N. piRNAs of Caenorhabditis elegans broadly silence nonself sequences through functionally random targeting. Nucleic Acids Res. 2022;50(3):1416–1429. PMCID: PMC8860604
- 1.Pyo A, Zhang Y, Wingreen N. Surface tension and super-stoichiometric surface enrichment in two-component biomolecular condensates. iScience. 2022;25(2):103852. PMCID: PMC8851291
- 1.Lopez J, Wingreen N. Noisy metabolism can promote microbial cross-feeding. Elife. 2022;11. PMCID: PMC8983042
- 1.Pareek V, Sha Z, He J, Wingreen N, Benkovic S. Metabolic channeling: predictions, deductions, and evidence. Mol Cell. 2021;81(18):3775–3785. PMCID: PMC8485759
- 1.Miangolarra M, Li S, Joanny J-F, Wingreen N, Castellana M. Steric interactions and out-of-equilibrium processes control the internal organization of bacteria. Proc Natl Acad Sci U S A. 2021;118(43). PMCID: PMC8639350
- 1.Erez A, Lopez J, Meir Y, Wingreen N. Enzyme regulation and mutation in a model serial-dilution ecosystem. Phys Rev E. 2021;104(4-1):044412. PMID: 34781576
- 1.Lopez J, Donia M, Wingreen N. Modeling the ecology of parasitic plasmids. ISME J. 2021;15(10):2843–2852. PMCID: PMC8443676
- 1.Narla A, Borenstein D, Wingreen N. A biophysical limit for quorum sensing in biofilms. Proc Natl Acad Sci U S A. 2021;118(21). PMCID: PMC8166027
- 1.Qin B, Fei C, Wang B, Stone H, Wingreen N, Bassler B. Hierarchical transitions and fractal wrinkling drive bacterial pellicle morphogenesis. Proc Natl Acad Sci U S A. 2021;118(20). PMCID: PMC8157956
- 1.Zhang Y, Xu B, Weiner B, Meir Y, Wingreen N. Decoding the physical principles of two-component biomolecular phase separation. Elife. 2021;10. PMCID: PMC7952089
- 1.Wong G, Antani J, Lele P, Chen J, Nan B, Kühn M, Persat A, Bru J-L, Høyland-Kroghsbo N, Siryaporn A, Conrad J, Carrara F, Yawata Y, Stocker R, Brun Y, Whitfield G, Lee C, de Anda J, Schmidt W, Golestanian R, O’Toole G, Floyd K, Yildiz F, Yang S, Jin F, Toyofuku M, Eberl L, Nomura N, Zacharoff L, El-Naggar M, Yalcin S, Malvankar N, Rojas-Andrade M, Hochbaum A, Yan J, Stone H, Wingreen N, Bassler B, Wu Y, Xu H, Drescher K, Dunkel J. Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation. Phys Biol. 2021;18(5). PMCID: PMC8506656
- 1.Saad-Roy C, Grenfell B, Levin S, van den Driessche P, Wingreen N. Evolution of an asymptomatic first stage of infection in a heterogeneous population. J R Soc Interface. 2021;18(179):20210175. PMCID: PMC8205539
- 1.Landajuela A, Braun M, Rodrigues C, Martínez-Calvo A, Doan T, Horenkamp F, Andronicos A, Shteyn V, Williams N, Lin C, Wingreen N, Rudner D, Karatekin E. FisB relies on homo-oligomerization and lipid binding to catalyze membrane fission in bacteria. PLoS Biol. 2021;19(6):e3001314. PMCID: PMC8274934
- 1.Saad-Roy C, Grenfell B, Levin S, Pellis L, Stage H, van den Driessche P, Wingreen N. Superinfection and the evolution of an initial asymptomatic stage. R Soc Open Sci. 2021;8(1):202212. PMCID: PMC7890506
- 1.Koch M, Fei C, Wingreen N, Shaevitz J, Gitai Z. Competitive binding of independent extension and retraction motors explains the quantitative dynamics of type IV pili. Proc Natl Acad Sci U S A. 2021;118(8). PMCID: PMC7923367
- 1.Jemielita M, Mashruwala A, Valastyan J, Wingreen N, Bassler B. Secreted Proteases Control the Timing of Aggregative Community Formation in Vibrio cholerae. mBio. 2021;12(6):e0151821. PMCID: PMC8609355
- 1.Weiner B, Pyo A, Meir Y, Wingreen N. Motif-pattern dependence of biomolecular phase separation driven by specific interactions. PLoS Comput Biol. 2021;17(12):e1009748. PMCID: PMC8751999
- 1.Lopez J, Donia M, Wingreen N. Publisher Correction: Modeling the ecology of parasitic plasmids. ISME J. 2021;15(12):3722. PMCID: PMC8630101
- 1.Erez A, Lopez J, Weiner B, Meir Y, Wingreen N. Nutrient levels and trade-offs control diversity in a serial dilution ecosystem. Elife. 2020;9. PMCID: PMC7486120
- 1.Saad-Roy C, Wingreen N, Levin S, Grenfell B. Dynamics in a simple evolutionary-epidemiological model for the evolution of an initial asymptomatic infection stage. Proc Natl Acad Sci U S A. 2020;117(21):11541–11550. PMCID: PMC7261016
- 1.Tareen A, Wingreen N, Mukhopadhyay R. Asymmetry between Activators and Deactivators in Functional Protein Networks. Sci Rep. 2020;10(1):10131. PMCID: PMC7311538
- 1.Saad-Roy C, Arinaminpathy N, Wingreen N, Levin S, Akey J, Grenfell B. Implications of localized charge for human influenza A H1N1 hemagglutinin evolution: Insights from deep mutational scans. PLoS Comput Biol. 2020;16(6):e1007892. PMCID: PMC7316228
- 1.Qin B, Fei C, Bridges A, Mashruwala A, Stone H, Wingreen N, Bassler B. Cell position fates and collective fountain flow in bacterial biofilms revealed by light-sheet microscopy. Science. 2020;369(6499):71–77. PMCID: PMC7426073
- 1.Li Z, Liu B, Li S, King C, Gitai Z, Wingreen N. Modeling microbial metabolic trade-offs in a chemostat. PLoS Comput Biol. 2020;16(8):e1008156. PMCID: PMC7482850
- 1.Fei C, Mao S, Yan J, Alert R, Stone H, Bassler B, Wingreen N, Košmrlj A. Nonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates. Proc Natl Acad Sci U S A. 2020;117(14):7622–7632. PMCID: PMC7148565
- 1.Rath S, Prangley E, Donovan J, Demarest K, Wingreen N, Meir Y, Korennykh A. Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in the dsRNA Response. Mol Cell. 2019;75(6):1218–1228.e6. PMCID: PMC6754276
- 1.Weiner B, Posfai A, Wingreen N. Spatial ecology of territorial populations. Proc Natl Acad Sci U S A. 2019;116(36):17874–17879. PMCID: PMC6731762
- 1.Mayer A, Zhang Y, Perelson A, Wingreen N. Regulation of T cell expansion by antigen presentation dynamics. Proc Natl Acad Sci U S A. 2019;116(13):5914–5919. PMCID: PMC6442601
- 1.Yan J, Fei C, Mao S, Moreau A, Wingreen N, Košmrlj A, Stone H, Bassler B. Mechanical instability and interfacial energy drive biofilm morphogenesis. Elife. 2019;8. PMCID: PMC6453567
- 1.Ali M, Huang K, Wingreen N, Mukhopadhyay R. Cell geometry and leaflet bilayer asymmetry regulate domain formation in plasma membranes. Phys Rev E. 2019;99(1-1):012401. PMCID: PMC6553634
- 1.Chitrakar A, Rath S, Donovan J, Demarest K, Li Y, Sridhar R, Weiss S, Kotenko S, Wingreen N, Korennykh A. Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L. Proc Natl Acad Sci U S A. 2019;116(6):2103–2111. PMCID: PMC6369740
- 1.Wang S-W, Bitbol A-F, Wingreen N. Revealing evolutionary constraints on proteins through sequence analysis. PLoS Comput Biol. 2019;15(4):e1007010. PMCID: PMC6502352
- 1.Beroz F, Yan J, Sabass B, Stone H, Bassler B, Wingreen N, Meir Y. Verticalization of bacterial biofilms. Nat Phys. 2018;14(9):954–960. PMCID: PMC6426328
- 1.Shin Y, Chang Y-C, Lee D, Berry J, Sanders D, Ronceray P, Wingreen N, Haataja M, Brangwynne C. Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome. Cell. 2018;175(6):1481–1491.e13. PMCID: PMC6724728
- 1.Yan J, Moreau A, Khodaparast S, Perazzo A, Feng J, Fei C, Mao S, Mukherjee S, Košmrlj A, Wingreen N, Bassler B, Stone H. Bacterial Biofilm Material Properties Enable Removal and Transfer by Capillary Peeling. Adv Mater. 2018;30(46):e1804153. PMCID: PMC8865467
- 1.Tareen A, Wingreen N, Mukhopadhyay R. Modeling evolution of crosstalk in noisy signal transduction networks. Phys Rev E. 2018;97(2-1):020402. PMCID: PMC5973540
- 1.Li S, Li Z, Park J, King C, Rabinowitz J, Wingreen N, Gitai Z. Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions. Nat Microbiol. 2018;3(8):939–947. PMCID: PMC6278830
- 1.Ali M, Wingreen N, Mukhopadhyay R. Hidden long evolutionary memory in a model biochemical network. Phys Rev E. 2018;97(4-1):040401. PMCID: PMC5973509
- 1.Rosenzweig E, Xu B, Cuellar L, Martinez-Sanchez A, Schaffer M, Strauss M, Cartwright H, Ronceray P, Plitzko J, Förster F, Wingreen N, Engel B, Mackinder L, Jonikas M. The Eukaryotic CO-Concentrating Organelle Is Liquid-like and Exhibits Dynamic Reorganization. Cell. 2017;171(1):148–162.e19. PMCID: PMC5671343
- 1.Taillefumier T, Posfai A, Meir Y, Wingreen N. Microbial consortia at steady supply. Elife. 2017;6. PMCID: PMC5419753