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Rama Ranganathan

InstitutionUniversity of Chicago
DepartmentBiochemistry and Molecular Biology
AddressChicago IL 60637
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    Collapse Overview 
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    The Problem:

    Evolution produces systems that display remarkable structural and functional properties that can rival or exceed the performance of man-made systems. For example, protein molecules fold spontaneously into precise, well-ordered structures and can carry out specific binding, catalysis of difficult chemical reactions, and allosteric regulation. At a larger spatial scale, networks of proteins assemble to form metabolic and signaling systems that show efficient and selective processing of material and information. These performance characteristics can coexist with robustness to random perturbation and the capacity to adapt to new functional states as conditions of selection vary in the environment. The goal of our laboratory is to understand the design principles that underlie structure, function, and adaptation in biological systems. For maximal experimental and theoretical power, we focus at the atomic to cellular scale.

    The Strategy:

    Our approach is to break the problem down into three essential tasks: (1) to define the pattern of constraints that specify biological systems, (2) to determine the underlying physics, and (3) to understand the generative process that produces these (and not other) architectures. In other words, we wish to understand what nature has built, how it works, and why it is built the way it is. Answers to these core questions lie at the essence of understanding and engineering biological systems, and more fundamentally, to explain how they are even possible through the random, algorithmic process that we call evolution. Read more about the three core directions and about current problems being addressed in our laboratory... .
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    Collapse Research 
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    R01GM141697     (RANGANATHAN, RAMA)Aug 1, 2021 - May 31, 2025
    Data-driven, evolution-based design of proteins
    Role: Principal Investigator

    P41GM118217     (RANGANATHAN, RAMA)Feb 1, 2019 - Jan 31, 2022
    BioCARS: Structural Dynamics and Biological Mechanisms
    Role: Principal Investigator

    R01GM123456     (RANGANATHAN, RAMA)Sep 7, 2016 - Jul 31, 2021
    Seeing Protein Mechanics: The Link Between Molecular Structure, Function, and Evolution
    Role: Principal Investigator

    R01EY018720     (RANGANATHAN, RAMA)Sep 1, 2007 - Nov 30, 2013
    Mechanistic analysis of dynamic scaffolding in a cellular signaling network
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Henning RW, Kosheleva I, Šrajer V, Kim IS, Zoellner E, Ranganathan R. BioCARS: Synchrotron facility for probing structural dynamics of biological macromolecules. Struct Dyn. 2024 Jan; 11(1):014301. PMID: 38304444; PMCID: PMC10834067.
    2. Praljak N, Lian X, Ranganathan R, Ferguson AL. ProtWave-VAE: Integrating Autoregressive Sampling with Latent-Based Inference for Data-Driven Protein Design. ACS Synth Biol. 2023 Dec 15; 12(12):3544-3561. PMID: 37988083; PMCID: PMC10911954.
      Citations: 1     Fields:    Translation:Cells
    3. Kleeorin Y, Russ WP, Ranganathan R, Rivoire O. Undersampling and the inference of coevolution in proteins. Cell Syst. 2023 03 15; 14(3):210-219.e7. PMID: 36693377; PMCID: PMC10911952.
      Citations: 1     Fields:    
    4. Murugan A, Husain K, Rust MJ, Hepler C, Bass J, Pietsch JMJ, Swain PS, Jena SG, Toettcher JE, Chakraborty AK, Sprenger KG, Wang S, Wood KB, Skanata A, Kussell E, Ranganathan R, Shih HY, Goldenfeld N, Mora T, Walczak AM, Rivoire O. Roadmap on biology in time varying environments. Phys Biol. 2021 05 17; 18(4). PMID: 33477124; PMCID: PMC8652373.
      Citations: 11     Fields:    
    5. Ferguson AL, Ranganathan R. 100th Anniversary of Macromolecular Science Viewpoint: Data-Driven Protein Design. ACS Macro Lett. 2021 03 16; 10(3):327-340. PMID: 35549066.
      Citations: 8     Fields:    Translation:Cells
    6. Walker AS, Russ WP, Ranganathan R, Schepartz A. RNA sectors and allosteric function within the ribosome. Proc Natl Acad Sci U S A. 2020 08 18; 117(33):19879-19887. PMID: 32747536; PMCID: PMC7443888.
      Citations: 7     Fields:    Translation:Cells
    7. Russ WP, Stocker C, Socolich M, Kast P, Hilvert D, Ranganathan R, Figliuzzi M, Barrat-Charlaix P, Monasson R, Cocco S, Weigt M. An evolution-based model for designing chorismate mutase enzymes. Science. 2020 07 24; 369(6502):440-445. PMID: 32703877.
      Citations: 82     Fields:    Translation:Cells
    8. Poelwijk FJ, Socolich M, Ranganathan R. Learning the pattern of epistasis linking genotype and phenotype in a protein. Nat Commun. 2019 09 16; 10(1):4213. PMID: 31527666; PMCID: PMC6746860.
      Citations: 44     Fields:    
    9. Ranganathan R. Putting Evolution to Work. Cell. 2018 11 29; 175(6):1449-1451. PMID: 30500528.
      Citations: 3     Fields:    Translation:Humans
    10. Creixell P, Pandey JP, Palmeri A, Bhattacharyya M, Creixell M, Ranganathan R, Pincus D, Yaffe MB. Hierarchical Organization Endows the Kinase Domain with Regulatory Plasticity. Cell Syst. 2018 10 24; 7(4):371-383.e4. PMID: 30243563; PMCID: PMC6202253.
      Citations: 9     Fields:    Translation:HumansCells
    11. Salinas VH, Ranganathan R. Coevolution-based inference of amino acid interactions underlying protein function. Elife. 2018 07 20; 7. PMID: 30024376; PMCID: PMC6117156.
      Citations: 50     Fields:    Translation:Cells
    12. Rosensweig C, Reynolds KA, Gao P, Laothamatas I, Shan Y, Ranganathan R, Takahashi JS, Green CB. An evolutionary hotspot defines functional differences between CRYPTOCHROMES. Nat Commun. 2018 03 19; 9(1):1138. PMID: 29556064; PMCID: PMC5859286.
      Citations: 44     Fields:    Translation:HumansAnimalsCells
    13. Subramanian SK, Russ WP, Ranganathan R. A set of experimentally validated, mutually orthogonal primers for combinatorially specifying genetic components. Synth Biol (Oxf). 2018; 3(1):ysx008. PMID: 32995509; PMCID: PMC7445780.
      Citations: 2     
    14. Bandaru P, Shah NH, Bhattacharyya M, Barton JP, Kondo Y, Cofsky JC, Gee CL, Chakraborty AK, Kortemme T, Ranganathan R, Kuriyan J. Deconstruction of the Ras switching cycle through saturation mutagenesis. Elife. 2017 07 07; 6. PMID: 28686159; PMCID: PMC5538825.
      Citations: 52     Fields:    Translation:HumansCells
    15. Hekstra DR, White KI, Socolich MA, Henning RW, Ranganathan R, Šrajer V. Electric-field-stimulated protein mechanics. Nature. 2016 12 15; 540(7633):400-405. PMID: 27926732; PMCID: PMC5730412.
      Citations: 75     Fields:    Translation:HumansCells
    16. Shah NH, Wang Q, Yan Q, Karandur D, Kadlecek TA, Fallahee IR, Russ WP, Ranganathan R, Weiss A, Kuriyan J. An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor. Elife. 2016 10 04; 5. PMID: 27700984; PMCID: PMC5089863.
      Citations: 50     Fields:    Translation:HumansCells
    17. Stiffler MA, Subramanian SK, Salinas VH, Ranganathan R. A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing. J Vis Exp. 2016 07 03; (113). PMID: 27403811; PMCID: PMC4993320.
      Citations: 2     Fields:    
    18. Poelwijk FJ, Krishna V, Ranganathan R. The Context-Dependence of Mutations: A Linkage of Formalisms. PLoS Comput Biol. 2016 06; 12(6):e1004771. PMID: 27337695; PMCID: PMC4919011.
      Citations: 40     Fields:    Translation:Cells
    19. Raman AS, White KI, Ranganathan R. Origins of Allostery and Evolvability in Proteins: A Case Study. Cell. 2016 Jul 14; 166(2):468-480. PMID: 27321669.
      Citations: 60     Fields:    Translation:AnimalsCells
    20. Reynolds KA, Ranganathan R, Rivoire O. Evolution-Based Functional Decomposition of Proteins. PLoS Comput Biol. 2016 06; 12(6):e1004817. PMID: 27254668; PMCID: PMC4890866.
      Citations: 55     Fields:    Translation:Cells
    21. Stiffler MA, Hekstra DR, Ranganathan R. Evolvability as a function of purifying selection in TEM-1 ß-lactamase. Cell. 2015 Feb 26; 160(5):882-892. PMID: 25723163.
      Citations: 135     Fields:    Translation:Cells
    22. Ma L, Ranganathan R. Systems-level characterization of the kernel mechanism of the cyanobacterial circadian oscillator. Biosystems. 2014 Mar; 117:30-9. PMID: 24444761.
      Citations:    Fields:    Translation:Cells
    23. Novinec M, Caflisch A, Ranganathan R, Baici A, Korenc M, Lenarcic B. A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods. Nat Commun. 2014; 5:3287. PMID: 24518821.
      Citations: 35     Fields:    Translation:HumansCells
    24. Reynolds KA, Russ WP, Socolich M, Ranganathan R. Evolution-based design of proteins. Methods Enzymol. 2013; 523:213-35. PMID: 23422432.
      Citations: 21     Fields:    Translation:Cells
    25. McLaughlin RN, Poelwijk FJ, Raman A, Gosal WS, Ranganathan R. The spatial architecture of protein function and adaptation. Nature. 2012 Nov 01; 491(7422):138-42. PMID: 23041932; PMCID: PMC3991786.
      Citations: 232     Fields:    Translation:Cells
    26. Ma L, Ranganathan R. Quantifying the rhythm of KaiB-C interaction for in vitro cyanobacterial circadian clock. PLoS One. 2012; 7(8):e42581. PMID: 22900029; PMCID: PMC3416856.
      Citations: 8     Fields:    Translation:Cells
    27. Reynolds KA, McLaughlin RN, Ranganathan R. Hot spots for allosteric regulation on protein surfaces. Cell. 2011 Dec 23; 147(7):1564-75. PMID: 22196731; PMCID: PMC3414429.
      Citations: 181     Fields:    Translation:Cells
    28. Smock RG, Rivoire O, Russ WP, Swain JF, Leibler S, Ranganathan R, Gierasch LM. An interdomain sector mediating allostery in Hsp70 molecular chaperones. Mol Syst Biol. 2010 Sep 21; 6:414. PMID: 20865007; PMCID: PMC2964120.
      Citations: 68     Fields:    Translation:AnimalsCells
    29. Levine B, Ranganathan R. Autophagy: Snapshot of the network. Nature. 2010 Jul 01; 466(7302):38-40. PMID: 20596005; PMCID: PMC3518437.
      Citations: 17     Fields:    Translation:HumansCells
    30. Halabi N, Rivoire O, Leibler S, Ranganathan R. Protein sectors: evolutionary units of three-dimensional structure. Cell. 2009 Aug 21; 138(4):774-86. PMID: 19703402; PMCID: PMC3210731.
      Citations: 331     Fields:    Translation:HumansAnimalsCells
    31. Lee J, Natarajan M, Nashine VC, Socolich M, Vo T, Russ WP, Benkovic SJ, Ranganathan R. Surface sites for engineering allosteric control in proteins. Science. 2008 Oct 17; 322(5900):438-42. PMID: 18927392; PMCID: PMC3071530.
      Citations: 155     Fields:    Translation:Cells
    32. Ranganathan R. Biochemistry. Signaling across the cell membrane. Science. 2007 Nov 23; 318(5854):1253-4. PMID: 18033872.
      Citations: 6     Fields:    Translation:Cells
    33. Mishra P, Socolich M, Wall MA, Graves J, Wang Z, Ranganathan R. Dynamic scaffolding in a G protein-coupled signaling system. Cell. 2007 Oct 05; 131(1):80-92. PMID: 17923089.
      Citations: 48     Fields:    Translation:AnimalsCells
    34. Laidlaw J, Gelfand Y, Ng KW, Garner HR, Ranganathan R, Benson G, Fondon JW. Elevated basal slippage mutation rates among the Canidae. J Hered. 2007; 98(5):452-60. PMID: 17437958.
      Citations: 22     Fields:    Translation:HumansAnimalsCells
    35. Ferguson AD, Amezcua CA, Halabi NM, Chelliah Y, Rosen MK, Ranganathan R, Deisenhofer J. Signal transduction pathway of TonB-dependent transporters. Proc Natl Acad Sci U S A. 2007 Jan 09; 104(2):513-8. PMID: 17197416; PMCID: PMC1760641.
      Citations: 50     Fields:    Translation:Cells
    36. Poole AM, Ranganathan R. Knowledge-based potentials in protein design. Curr Opin Struct Biol. 2006 Aug; 16(4):508-13. PMID: 16843652.
      Citations: 36     Fields:    
    37. Natarajan M, Lin KM, Hsueh RC, Sternweis PC, Ranganathan R. A global analysis of cross-talk in a mammalian cellular signalling network. Nat Cell Biol. 2006 Jun; 8(6):571-80. PMID: 16699502.
      Citations: 106     Fields:    Translation:AnimalsCells
    38. Socolich M, Lockless SW, Russ WP, Lee H, Gardner KH, Ranganathan R. Evolutionary information for specifying a protein fold. Nature. 2005 Sep 22; 437(7058):512-8. PMID: 16177782.
      Citations: 159     Fields:    Translation:Cells
    39. Russ WP, Lowery DM, Mishra P, Yaffe MB, Ranganathan R. Natural-like function in artificial WW domains. Nature. 2005 Sep 22; 437(7058):579-83. PMID: 16177795.
      Citations: 111     Fields:    Translation:Cells
    40. Shulman AI, Larson C, Mangelsdorf DJ, Ranganathan R. Structural determinants of allosteric ligand activation in RXR heterodimers. Cell. 2004 Feb 06; 116(3):417-29. PMID: 15016376.
      Citations: 124     Fields:    Translation:HumansCells
    41. Jain RK, Ranganathan R. Local complexity of amino acid interactions in a protein core. Proc Natl Acad Sci U S A. 2004 Jan 06; 101(1):111-6. PMID: 14684834; PMCID: PMC314147.
      Citations: 16     Fields:    Translation:Cells
    42. Hatley ME, Lockless SW, Gibson SK, Gilman AG, Ranganathan R. Allosteric determinants in guanine nucleotide-binding proteins. Proc Natl Acad Sci U S A. 2003 Nov 25; 100(24):14445-50. PMID: 14623969; PMCID: PMC283611.
      Citations: 61     Fields:    Translation:AnimalsCells
    43. Ranganathan R. Cell biology. A matter of life or death. Science. 2003 Mar 14; 299(5613):1677-9. PMID: 12637727.
      Citations: 6     Fields:    Translation:HumansAnimalsCells
    44. Lockless SW, Wall MA, Ranganathan R, Süel GM. Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nat Struct Biol. 2003 Jan; 10(1):59-69. PMID: 12483203.
      Citations: 388     Fields:    Translation:Cells
    45. Gilman AG, Simon MI, Bourne HR, Harris BA, Long R, Ross EM, Stull JT, Taussig R, Arkin AP, Cobb MH, Cyster JG, Devreotes PN, Ferrell JE, Fruman D, Gold M, Weiss A, Berridge MJ, Cantley LC, Catterall WA, Coughlin SR, Olson EN, Smith TF, Brugge JS, Botstein D, Dixon JE, Hunter T, Lefkowitz RJ, Pawson AJ, Sternberg PW, Varmus H, Subramaniam S, Sinkovits RS, Li J, Mock D, Ning Y, Saunders B, Sternweis PC, Hilgemann D, Scheuermann RH, DeCamp D, Hsueh R, Lin KM, Ni Y, Seaman WE, Simpson PC, O'Connell TD, Roach T, Choi S, Eversole-Cire P, Fraser I, Mumby MC, Zhao Y, Brekken D, Shu H, Meyer T, Chandy G, Heo WD, Liou J, O'Rourke N, Verghese M, Mumby SM, Han H, Brown HA, Forrester JS, Ivanova P, Milne SB, Casey PJ, Harden TK, Doyle J, Gray ML, Michnick S, Schmidt MA, Toner M, Tsien RY, Natarajan M, Ranganathan R, Sambrano GR, Participating investigators and scientists of the Alliance for Cellular Signaling. Overview of the Alliance for Cellular Signaling. Nature. 2002 Dec 12; 420(6916):703-6. PMID: 12478301.
      Citations: 38     Fields:    Translation:HumansCells
    46. Russ WP, Ranganathan R. Knowledge-based potential functions in protein design. Curr Opin Struct Biol. 2002 Aug; 12(4):447-52. PMID: 12163066.
      Citations: 22     Fields:    Translation:Cells
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