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Rama Ranganathan

TitleProfessor
InstitutionUniversity of Chicago
DepartmentBiochem/Mol Bio
AddressChicago IL 60637
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    Collapse Overview 
    Collapse overview
    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 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.
    List All   |   Timeline
    1. Poelwijk FJ, Socolich M, Ranganathan R. Learning the pattern of epistasis linking genotype and phenotype in a protein. Nat Commun. 2019 Sep 16; 10(1):4213. PMID: 31527666.
      View in: PubMed
    2. Ranganathan R. Putting Evolution to Work. Cell. 2018 11 29; 175(6):1449-1451. PMID: 30500528.
      View in: PubMed
    3. 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.
      View in: PubMed
    4. Salinas VH, Ranganathan R. Coevolution-based inference of amino acid interactions underlying protein function. Elife. 2018 07 20; 7. PMID: 30024376.
      View in: PubMed
    5. 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.
      View in: PubMed
    6. 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.
      View in: PubMed
    7. Hekstra DR, White KI, Socolich MA, Henning RW, Šrajer V, Ranganathan R. Electric-field-stimulated protein mechanics. Nature. 2016 12 15; 540(7633):400-405. PMID: 27926732.
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    8. 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.
      View in: PubMed
    9. 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.
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    10. 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.
      View in: PubMed
    11. 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.
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    12. Rivoire O, Reynolds KA, Ranganathan R. Evolution-Based Functional Decomposition of Proteins. PLoS Comput Biol. 2016 06; 12(6):e1004817. PMID: 27254668.
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    13. 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.
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    14. Ma L, Ranganathan R. Systems-level characterization of the kernel mechanism of the cyanobacterial circadian oscillator. Biosystems. 2014 Mar; 117:30-9. PMID: 24444761.
      View in: PubMed
    15. Novinec M, Korenc M, Caflisch A, Ranganathan R, Lenarcic B, Baici A. A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods. Nat Commun. 2014; 5:3287. PMID: 24518821.
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    16. Reynolds KA, Russ WP, Socolich M, Ranganathan R. Evolution-based design of proteins. Methods Enzymol. 2013; 523:213-35. PMID: 23422432.
      View in: PubMed
    17. 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.
      View in: PubMed
    18. 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.
      View in: PubMed
    19. Reynolds KA, McLaughlin RN, Ranganathan R. Hot spots for allosteric regulation on protein surfaces. Cell. 2011 Dec 23; 147(7):1564-75. PMID: 22196731.
      View in: PubMed
    20. 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.
      View in: PubMed
    21. Levine B, Ranganathan R. Autophagy: Snapshot of the network. Nature. 2010 Jul 01; 466(7302):38-40. PMID: 20596005.
      View in: PubMed
    22. 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.
      View in: PubMed
    23. 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.
      View in: PubMed
    24. Ranganathan R. Biochemistry. Signaling across the cell membrane. Science. 2007 Nov 23; 318(5854):1253-4. PMID: 18033872.
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    25. 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.
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    26. 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.
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    27. 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.
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    28. Poole AM, Ranganathan R. Knowledge-based potentials in protein design. Curr Opin Struct Biol. 2006 Aug; 16(4):508-13. PMID: 16843652.
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    29. 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.
      View in: PubMed
    30. 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.
      View in: PubMed
    31. 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.
      View in: PubMed
    32. 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.
      View in: PubMed
    33. 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.
      View in: PubMed
    34. 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.
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    35. Ranganathan R. Cell biology. A matter of life or death. Science. 2003 Mar 14; 299(5613):1677-9. PMID: 12637727.
      View in: PubMed
    36. Süel GM, Lockless SW, Wall MA, Ranganathan R. Evolutionarily conserved networks of residues mediate allosteric communication in proteins. Nat Struct Biol. 2003 Jan; 10(1):59-69. PMID: 12483203.
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    37. Gilman AG, Simon MI, Bourne HR, Harris BA, Long R, Ross EM, Stull JT, Taussig R, Bourne HR, Arkin AP, Cobb MH, Cyster JG, Devreotes PN, Ferrell JE, Fruman D, Gold M, Weiss A, Stull JT, 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, Simon MI, 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, Arkin AP, Doyle J, Gray ML, Meyer T, Michnick S, Schmidt MA, Toner M, Tsien RY, Natarajan M, Ranganathan R, Sambrano GR. Overview of the Alliance for Cellular Signaling. Nature. 2002 Dec 12; 420(6916):703-6. PMID: 12478301.
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    38. Russ WP, Ranganathan R. Knowledge-based potential functions in protein design. Curr Opin Struct Biol. 2002 Aug; 12(4):447-52. PMID: 12163066.
      View in: PubMed
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