Carl H. Johnson, Ph.D.


Visit Lab Site

Faculty Appointments
Professor of Biological Sciences Professor of Molecular Physiology and BiophysicsStevenson Chair of Biological Sciences
Ph.D., Cellular and Molecular Biology, Stanford University, Stanford, CaliforniaB.A., University of Texas, Austin, Texas
Office Address
Office @ U-8211 MCN (Learned Labs)
Mail @ Box 1634 Sta B
Nashville, TN 37235
Research Description
Organisms and even single cells have endogenous biological "clocks" that allow them to tell the time of day. Research in our laboratory is directed towards understanding the cellular and molecular bases of these fascinating timing mechanisms in a variety of organisms: cyanobacteria ("blue-green algae"), plants, and animals. To analyze the molecular nature of the clock in the prokaryotic cyanobacteria, we have developed a bioluminescent reporter strain that expresses a daily rhythm of light emission. Using this bioluminescence rhythm as a marker, clock mutants have been identified. We found that the essential clock gene, KaiC, is rhythmically expressed and forms ATP-dependent hexamers. In collaboration with the laboratory of Dr. Martin Egli, we have crystallized KaiC to determine its three-dimensional structure and discover its phosphorylation sites. The three key bacterial clock proteins (KaiA + KaiB + KaiC) will show circadian oscillations in a test tube! In collaboration with the laboratories of Drs. Phoebe Stewart and Hassane Mchaourab, we are applying electron microscopic and biophysical methods to explain how these proteins oscillate in vitro. Furthermore, we are using clock mutants of cyanobacteria to provide the first rigorous evidence for the adaptive significance of circadian clocks in fitness.

We also study the neuroscience of the circadian system of mammals. To measure circadian rhythms in brain slices in vitro, we use transgenic mice that express luciferase rhythmically. As a model system, we have also created a fibroblast cell line that is stably transfected with a luciferase reporter and glows rhythmically. Therefore, we use luminescence as a tool to monitor circadian rhythms in the brain. Future studies will focus upon understanding the signal transduction pathway of calcium to the clock and the role of clock genes in the fundamental mammalian clockwork.

We have recently extended our studies to the genetics of the human biological clock. We are examining clock gene polymorphisms in human populations to determine how the neurogenetics of the biological clock affects our ability to adapt to shiftwork cycles and how it can influence mental health (esp. depression). Because daily biological clocks control a myriad of fundamental cellular activities, including cell division, metabolism, gene expression, and ion channel, the elucidation of the timing mechanism will have ramifications for many aspects of temporal regulation, including mental health, cancer, and jet lag.

Finally, we have developed a new method for measuring protein-protein interactions based upon the resonance energy between a luciferase and a fluorescent protein. This method is called Bioluminescence Resonance Energy Transfer, or BRET. This technique has allowed us to develop novel reporters for intracellular calcium and hydrogen ions. We envision a bright future for this technique.

See our laboratory website at:
Research Keywords
Cellular and Molecular Biology of Biological Clocks
Veatch OJ, Pendergast JS, Allen MJ, Leu RM, Johnson CH, Elsea SH, Malow BA. Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay. J Autism Dev Disord. 2015 Jan; 45(1): 100-10. PMID: 25059483, PMCID: PMC4289108, DOI: 10.1007/s10803-014-2197-4, ISSN: 1573-3432.

Pattanayek R, Xu Y, Lamichhane A, Johnson CH, Egli M. An arginine tetrad as mediator of input-dependent and input-independent ATPases in the clock protein KaiC. Acta Crystallogr. D Biol. Crystallogr [print-electronic]. 2014 May; 70(Pt 5): 1375-90. PMID: 24816106, PII: S1399004714003228, DOI: 10.1107/S1399004714003228, ISSN: 1399-0047.

Yan Y, Jiang L, Aufderheide KJ, Wright GA, Terekhov A, Costa L, Qin K, McCleery WT, Fellenstein JJ, Ustione A, Robertson JB, Johnson CH, Piston DW, Hutson MS, Wikswo JP, Hofmeister W, Janetopoulos C. A microfluidic-enabled mechanical microcompressor for the immobilization of live single- and multi-cellular specimens. Microsc. Microanal [print-electronic]. 2014 Feb; 20(1): 141-51. PMID: 24444078, PMCID: PMC4026272, PII: S1431927613014037, DOI: 10.1017/S1431927613014037, ISSN: 1435-8115.

Johnson CH, Egli M. Metabolic compensation and circadian resilience in prokaryotic cyanobacteria. Annu. Rev. Biochem. 2014; 83: 221-47. PMID: 24905782, PMCID: PMC4259047, DOI: 10.1146/annurev-biochem-060713-035632, ISSN: 1545-4509.

Robertson JB, Davis CR, Johnson CH. Visible light alters yeast metabolic rhythms by inhibiting respiration. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Dec 12/24/2013; 110(52): 21130-5. PMID: 24297928, PMCID: PMC3876234, PII: 1313369110, DOI: 10.1073/pnas.1313369110, ISSN: 1091-6490.

Xu Y, Weyman PD, Umetani M, Xiong J, Qin X, Xu Q, Iwasaki H, Johnson CH. Circadian yin-yang regulation and its manipulation to globally reprogram gene expression. Curr. Biol [print-electronic]. 2013 Dec 12/2/2013; 23(23): 2365-74. PMID: 24210617, PMCID: PMC3889637, PII: S0960-9822(13)01251-7, DOI: 10.1016/j.cub.2013.10.011, ISSN: 1879-0445.

de la Iglesia HO, Johnson CH. Biological clocks: riding the tides. Curr. Biol. 2013 Oct 10/21/2013; 23(20): R921-3. PMID: 24156810, PMCID: PMC4307598, PII: S0960-9822(13)01118-4, DOI: 10.1016/j.cub.2013.09.006, ISSN: 1879-0445.

Egli M, Johnson CH. A circadian clock nanomachine that runs without transcription or translation. Curr. Opin. Neurobiol [print-electronic]. 2013 Oct; 23(5): 732-40. PMID: 23571120, PMCID: PMC3735861, PII: S0959-4388(13)00060-3, DOI: 10.1016/j.conb.2013.02.012, ISSN: 1873-6882.

Bittman EL, Johnson CH. Animal care practices in research on biological rhythms and sleep [editorial]. J. Biol. Rhythms. 2013 Oct; 28(5): 303-4. PMID: 24132055, PII: 28/5/303, DOI: 10.1177/0748730413502313, ISSN: 1552-4531.

Ma P, Woelfle MA, Johnson CH. An Evolutionary Fitness Enhancement Conferred by the Circadian System in Cyanobacteria. Chaos Solitons Fractals. 2013 May 5/1/2013; 50: 65-74. PMID: 23626410, PMCID: PMC3633149, DOI: 10.1016/j.chaos.2012.11.006, ISSN: 0960-0779.

Xu Y, Ma P, Shah P, Rokas A, Liu Y, Johnson CH. Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature [print-electronic]. 2013 Mar 3/7/2013; 495(7439): 116-20. PMID: 23417065, PMCID: PMC3593822, PII: nature11942, DOI: 10.1038/nature11942, ISSN: 1476-4687.

Shi SQ, Ansari TS, McGuinness OP, Wasserman DH, Johnson CH. Circadian disruption leads to insulin resistance and obesity. Curr. Biol [print-electronic]. 2013 Mar 3/4/2013; 23(5): 372-81. PMID: 23434278, PMCID: PMC3595381, PII: S0960-9822(13)00083-3, DOI: 10.1016/j.cub.2013.01.048, ISSN: 1879-0445.

Egli M, Pattanayek R, Sheehan JH, Xu Y, Mori T, Smith JA, Johnson CH. Loop-loop interactions regulate KaiA-stimulated KaiC phosphorylation in the cyanobacterial KaiABC circadian clock. Biochemistry [print-electronic]. 2013 Feb 2/19/2013; 52(7): 1208-20. PMID: 23351065, PMCID: PMC3587310, DOI: 10.1021/bi301691a, ISSN: 1520-4995.

Gamble KL, Resuehr D, Johnson CH. Shift work and circadian dysregulation of reproduction. Front Endocrinol (Lausanne). 2013; 4: 92. PMID: 23966978, PMCID: PMC3736045, DOI: 10.3389/fendo.2013.00092, ISSN: 1664-2392.

Edgar RS, Green EW, Zhao Y, van Ooijen G, Olmedo M, Qin X, Xu Y, Pan M, Valekunja UK, Feeney KA, Maywood ES, Hastings MH, Baliga NS, Merrow M, Millar AJ, Johnson CH, Kyriacou CP, O'Neill JS, Reddy AB. Peroxiredoxins are conserved markers of circadian rhythms. Nature. 2012 May 5/24/2012; 485(7399): 459-64. PMID: 22622569, PMCID: PMC3398137, PII: nature11088, DOI: 10.1038/nature11088, ISSN: 1476-4687.

Egli M, Mori T, Pattanayek R, Xu Y, Qin X, Johnson CH. Dephosphorylation of the core clock protein KaiC in the cyanobacterial KaiABC circadian oscillator proceeds via an ATP synthase mechanism. Biochemistry [print-electronic]. 2012 Feb 2/28/2012; 51(8): 1547-58. PMID: 22304631, PMCID: PMC3293397, DOI: 10.1021/bi201525n, ISSN: 1520-4995.

Zhang Y, Xie Q, Robertson JB, Johnson CH. PHlash: a new genetically encoded and ratiometric luminescence sensor of intracellular pH. PLoS ONE [print-electronic]. 2012; 7(8): e43072. PMID: 22905204, PMCID: PMC3419163, PII: PONE-D-12-00656, DOI: 10.1371/journal.pone.0043072, ISSN: 1932-6203.

Gamble KL, Motsinger-Reif AA, Hida A, Borsetti HM, Servick SV, Ciarleglio CM, Robbins S, Hicks J, Carver K, Hamilton N, Wells N, Summar ML, McMahon DG, Johnson CH. Shift work in nurses: contribution of phenotypes and genotypes to adaptation. PLoS ONE. 2011; 6(4): e18395. PMID: 21533241, PMCID: PMC3076422, DOI: 10.1371/journal.pone.0018395, ISSN: 1932-6203.

Robertson JB, Johnson CH. Luminescence as a continuous real-time reporter of promoter activity in yeast undergoing respiratory oscillations or cell division rhythms. Methods Mol. Biol. 2011; 734: 63-79. PMID: 21468985, PMCID: PMC3433746, DOI: 10.1007/978-1-61779-086-7_4, ISSN: 1940-6029.

Johnson CH, Stewart PL, Egli M. The cyanobacterial circadian system: from biophysics to bioevolution. Annu Rev Biophys. 2011; 40: 143-67. PMID: 21332358, PMCID: PMC3093959, DOI: 10.1146/annurev-biophys-042910-155317, ISSN: 1936-1238.

Xie Q, Soutto M, Xu X, Zhang Y, Johnson CH. Bioluminescence resonance energy transfer (BRET) imaging in plant seedlings and mammalian cells. Methods Mol. Biol. 2011; 680: 3-28. PMID: 21153370, PMCID: PMC3432581, DOI: 10.1007/978-1-60761-901-7_1, ISSN: 1940-6029.

Pattanayek R, Williams DR, Rossi G, Weigand S, Mori T, Johnson CH, Stewart PL, Egli M. Combined SAXS/EM based models of the S. elongatus post-translational circadian oscillator and its interactions with the output His-kinase SasA. PLoS ONE [print-electronic]. 2011; 6(8): e23697. PMID: 21887298, PMCID: PMC3161067, PII: PONE-D-11-10289, DOI: 10.1371/journal.pone.0023697, ISSN: 1932-6203.

Johnson CH. Circadian clocks and cell division: what's the pacemaker?. Cell Cycle [print-electronic]. 2010 Oct 10/1/2010; 9(19): 3864-73. PMID: 20890114, PMCID: PMC3047750, PII: 13205, ISSN: 1551-4005.

Qin X, Byrne M, Mori T, Zou P, Williams DR, McHaourab H, Johnson CH. Intermolecular associations determine the dynamics of the circadian KaiABC oscillator. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Aug 8/17/2010; 107(33): 14805-10. PMID: 20679240, PMCID: PMC2930409, PII: 1002119107, DOI: 10.1073/pnas.1002119107, ISSN: 1091-6490.

Shi S, Hida A, McGuinness OP, Wasserman DH, Yamazaki S, Johnson CH. Circadian clock gene Bmal1 is not essential; functional replacement with its paralog, Bmal2. Curr. Biol [print-electronic]. 2010 Feb 2/23/2010; 20(4): 316-21. PMID: 20153195, PMCID: PMC2907674, PII: S0960-9822(09)02158-7, DOI: 10.1016/j.cub.2009.12.034, ISSN: 1879-0445.

Qin X, Byrne M, Xu Y, Mori T, Johnson CH. Coupling of a core post-translational pacemaker to a slave transcription/translation feedback loop in a circadian system. PLoS Biol. 2010; 8(6): e1000394. PMID: 20563306, PMCID: PMC2885980, DOI: 10.1371/journal.pbio.1000394, ISSN: 1545-7885.

Xu X, Graeff R, Xie Q, Gamble KL, Mori T, Johnson CH. Comment on "The Arabidopsis circadian clock incorporates a cADPR-based feedback loop". Science. 2009 Oct 10/9/2009; 326(5950): 230; author reply 230. PMID: 19815758, PMCID: PMC2934760, PII: 326/5950/230-b, DOI: 10.1126/science.1169503, ISSN: 1095-9203.

Robertson JB, Zhang Y, Johnson CH. Light-emitting diode flashlights as effective and inexpensive light sources for fluorescence microscopy. J Microsc. 2009 Oct; 236(1): 1-4. PMID: 19772530, PMCID: PMC2751867, PII: JMI3208, DOI: 10.1111/j.1365-2818.2009.03208.x, ISSN: 1365-2818.

Pattanayek R, Mori T, Xu Y, Pattanayek S, Johnson CH, Egli M. Structures of KaiC circadian clock mutant proteins: a new phosphorylation site at T426 and mechanisms of kinase, ATPase and phosphatase. PLoS ONE. 2009; 4(11): e7529. PMID: 19956664, PMCID: PMC2777353, DOI: 10.1371/journal.pone.0007529, ISSN: 1932-6203.

Xu Y, Mori T, Qin X, Yan H, Egli M, Johnson CH. Intramolecular regulation of phosphorylation status of the circadian clock protein KaiC. PLoS ONE. 2009; 4(11): e7509. PMID: 19946629, PMCID: PMC2778140, DOI: 10.1371/journal.pone.0007509, ISSN: 1932-6203.

J.L. Ditty, S.R. Mackey, C.H. Johnson, editors. Bacterial Circadian Programs. [place unknown: publisher unknown]; 2009.

Robertson JB, Stowers CC, Boczko E, Johnson CH. Real-time luminescence monitoring of cell-cycle and respiratory oscillations in yeast. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Nov 11/18/2008; 105(46): 17988-93. PMID: 19004762, PMCID: PMC2584751, PII: 0809482105, DOI: 10.1073/pnas.0809482105, ISSN: 1091-6490.

Johnson CH, Egli M, Stewart PL. Structural insights into a circadian oscillator. Science. 2008 Oct 10/31/2008; 322(5902): 697-701. PMID: 18974343, PMCID: PMC2588432, PII: 322/5902/697, DOI: 10.1126/science.1150451, ISSN: 1095-9203.

Vougogiannopoulou K, Ferandin Y, Bettayeb K, Myrianthopoulos V, Lozach O, Fan Y, Johnson CH, Magiatis P, Skaltsounis AL, Mikros E, Meijer L. Soluble 3',6-substituted indirubins with enhanced selectivity toward glycogen synthase kinase -3 alter circadian period. J. Med. Chem [print-electronic]. 2008 Oct 10/23/2008; 51(20): 6421-31. PMID: 18816110, PMCID: PMC2717725, DOI: 10.1021/jm800648y, ISSN: 1520-4804.

Johnson CH, Mori T, Xu Y. A cyanobacterial circadian clockwork. Curr. Biol. 2008 Sep 9/9/2008; 18(17): R816-R825. PMID: 18786387, PMCID: PMC2585598, PII: S0960-9822(08)00877-4, DOI: 10.1016/j.cub.2008.07.012, ISSN: 0960-9822.

Ciarleglio CM, Ryckman KK, Servick SV, Hida A, Robbins S, Wells N, Hicks J, Larson SA, Wiedermann JP, Carver K, Hamilton N, Kidd KK, Kidd JR, Smith JR, Friedlaender J, McMahon DG, Williams SM, Summar ML, Johnson CH. Genetic differences in human circadian clock genes among worldwide populations. J. Biol. Rhythms. 2008 Aug; 23(4): 330-40. PMID: 18663240, PMCID: PMC2579796, PII: 23/4/330, DOI: 10.1177/0748730408320284, ISSN: 0748-7304.

Pattanayek R, Williams DR, Pattanayek S, Mori T, Johnson CH, Stewart PL, Egli M. Structural model of the circadian clock KaiB-KaiC complex and mechanism for modulation of KaiC phosphorylation. EMBO J [print-electronic]. 2008 Jun 6/18/2008; 27(12): 1767-78. PMID: 18497745, PMCID: PMC2435126, PII: emboj2008104, DOI: 10.1038/emboj.2008.104, ISSN: 1460-2075.

Bonneau R, Facciotti MT, Reiss DJ, Schmid AK, Pan M, Kaur A, Thorsson V, Shannon P, Johnson MH, Bare JC, Longabaugh W, Vuthoori M, Whitehead K, Madar A, Suzuki L, Mori T, Chang DE, Diruggiero J, Johnson CH, Hood L, Baliga NS. A predictive model for transcriptional control of physiology in a free living cell. Cell. 2007 Dec 12/28/2007; 131(7): 1354-65. PMID: 18160043, PII: S0092-8674(07)01416-X, DOI: 10.1016/j.cell.2007.10.053, ISSN: 0092-8674.

Woelfle MA, Xu Y, Qin X, Johnson CH. Circadian rhythms of superhelical status of DNA in cyanobacteria. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Nov 11/20/2007; 104(47): 18819-24. PMID: 18000054, PMCID: PMC2141860, PII: 0706069104, DOI: 10.1073/pnas.0706069104, ISSN: 1091-6490.

Xu X, Hotta CT, Dodd AN, Love J, Sharrock R, Lee YW, Xie Q, Johnson CH, Webb AA. Distinct light and clock modulation of cytosolic free Ca2+ oscillations and rhythmic CHLOROPHYLL A/B BINDING PROTEIN2 promoter activity in Arabidopsis. Plant Cell [print-electronic]. 2007 Nov; 19(11): 3474-90. PMID: 17982000, PMCID: PMC2174886, PII: tpc.106.046011, DOI: 10.1105/tpc.106.046011, ISSN: 1040-4651.

Fan Y, Hida A, Anderson DA, Izumo M, Johnson CH. Cycling of CRYPTOCHROME proteins is not necessary for circadian-clock function in mammalian fibroblasts. Curr. Biol [print-electronic]. 2007 Jul 7/3/2007; 17(13): 1091-100. PMID: 17583506, PMCID: PMC3434691, PII: S0960-9822(07)01472-8, DOI: 10.1016/j.cub.2007.05.048, ISSN: 0960-9822.

Xu X, Soutto M, Xie Q, Servick S, Subramanian C, von Arnim AG, Johnson CH. Imaging protein interactions with bioluminescence resonance energy transfer (BRET) in plant and mammalian cells and tissues. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Jun 6/12/2007; 104(24): 10264-9. PMID: 17551013, PMCID: PMC1891211, PII: 0701987104, DOI: 10.1073/pnas.0701987104, ISSN: 0027-8424.

Mori T, Williams DR, Byrne MO, Qin X, Egli M, Mchaourab HS, Stewart PL, Johnson CH. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol. 2007 Apr; 5(4): e93. PMID: 17388688, PMCID: PMC1831719, PII: 06-PLBI-RA-2188R2, DOI: 10.1371/journal.pbio.0050093, ISSN: 1545-7885.

Johnson CH. Bacterial circadian programs. Cold Spring Harb. Symp. Quant. Biol. 2007; 72: 395-404. PMID: 18419297, DOI: 10.1101/sqb.2007.72.027, ISSN: 0091-7451.

Woelfle MA, Johnson CH. No promoter left behind: global circadian gene expression in cyanobacteria. J. Biol. Rhythms. 2006 Dec; 21(6): 419-31. PMID: 17107933, PMCID: PMC3431602, PII: 21/6/419, DOI: 10.1177/0748730406294418, ISSN: 0748-7304.

Izumo M, Sato TR, Straume M, Johnson CH. Quantitative analyses of circadian gene expression in mammalian cell cultures. PLoS Comput. Biol. 2006 Oct; 2(10): e136. PMID: 17040123, PMCID: PMC1599765, PII: 06-PLCB-RA-0163R2, DOI: 10.1371/journal.pcbi.0020136, ISSN: 1553-7358.

Subramanian C, Woo J, Cai X, Xu X, Servick S, Johnson CH, Nebenführ A, von Arnim AG. A suite of tools and application notes for in vivo protein interaction assays using bioluminescence resonance energy transfer (BRET). Plant J [print-electronic]. 2006 Oct; 48(1): 138-52. PMID: 16925598, PII: TPJ2851, DOI: 10.1111/j.1365-313X.2006.02851.x, ISSN: 0960-7412.

Pattanayek R, Williams DR, Pattanayek S, Xu Y, Mori T, Johnson CH, Stewart PL, Egli M. Analysis of KaiA-KaiC protein interactions in the cyano-bacterial circadian clock using hybrid structural methods. EMBO J [print-electronic]. 2006 May 5/3/2006; 25(9): 2017-28. PMID: 16628225, PMCID: PMC1456936, PII: 7601086, DOI: 10.1038/sj.emboj.7601086, ISSN: 0261-4189.

Johnson, C.H., and S.S. Golden. Circadian Rhythms in Cyanobacteria. In: Nature Encyclopedia of Life Sciences, Nature Publishing Group, London: 2006.

Johnson, C.H.. Reminiscences from Pittendrigh's last Ph.D. student. Resonance. 2006; 11: 22-31.

Johnson, C.H., R. Shingles, and W.F. Ettinger. In: The Structure and Function of Plastids, Chapter 20. [place unknown: publisher unknown]; 2006. (23).

Mittag M, Kiaulehn S, Johnson CH. The circadian clock in Chlamydomonas reinhardtii. What is it for? What is it similar to?. Plant Physiol. 2005 Feb; 137(2): 399-409. PMID: 15710681, PMCID: PMC1065344, PII: 137/2/399, DOI: 10.1104/pp.104.052415, ISSN: 0032-0889.

Johnson CH. Testing the adaptive value of circadian systems. Meth. Enzymol. 2005; 393: 818-37. PMID: 15817326, PII: S0076687905930437, DOI: 10.1016/S0076-6879(05)93043-7, ISSN: 1557-7988.

Johnson, C.H. Testing the adaptive value of circadian systems. Methods in Enzymology. 2005; 393: 818-37.

Soutto M., Y. Xu, and C. H. Johnson. Bioluminescence RET (BRET): techniques and potential. In: Molecular Imaging: FRET Microscopy and Spectroscopy. 2005; 260-71.

Johnson, C.H. and C.P. Kyriacou. In: Endogenous Plant Rhythms. [place unknown: publisher unknown]; 2005.

Xu Y, Mori T, Pattanayek R, Pattanayek S, Egli M, Johnson CH. Identification of key phosphorylation sites in the circadian clock protein KaiC by crystallographic and mutagenetic analyses. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Sep 9/21/2004; 101(38): 13933-8. PMID: 15347809, PMCID: PMC518856, PII: 0404768101, DOI: 10.1073/pnas.0404768101, ISSN: 0027-8424.

Woelfle MA, Ouyang Y, Phanvijhitsiri K, Johnson CH. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr. Biol. 2004 Aug 8/24/2004; 14(16): 1481-6. PMID: 15324665, PII: S0960982204006062, DOI: 10.1016/j.cub.2004.08.023, ISSN: 0960-9822.

Pattanayek R, Wang J, Mori T, Xu Y, Johnson CH, Egli M. Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Mol. Cell. 2004 Aug 8/13/2004; 15(3): 375-88. PMID: 15304218, PII: S1097276504004356, DOI: 10.1016/j.molcel.2004.07.013, ISSN: 1097-2765.

Johnson CH. Precise circadian clocks in prokaryotic cyanobacteria. Curr Issues Mol Biol. 2004 Jul; 6(2): 103-10. PMID: 15119821, ISSN: 1467-3037.

Subramanian C, Kim BH, Lyssenko NN, Xu X, Johnson CH, von Arnim AG. The Arabidopsis repressor of light signaling, COP1, is regulated by nuclear exclusion: mutational analysis by bioluminescence resonance energy transfer. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2004 Apr 4/27/2004; 101(17): 6798-802. PMID: 15084749, PMCID: PMC404125, PII: 0307964101, DOI: 10.1073/pnas.0307964101, ISSN: 0027-8424.

Min H, Liu Y, Johnson CH, Golden SS. Phase determination of circadian gene expression in Synechococcus elongatus PCC 7942. J. Biol. Rhythms. 2004 Apr; 19(2): 103-12. PMID: 15038850, DOI: 10.1177/0748730403262056, ISSN: 0748-7304.

Johnson CH. Global orchestration of gene expression by the biological clock of cyanobacteria. Genome Biol [print-electronic]. 2004; 5(4): 217. PMID: 15059250, PMCID: PMC395776, PII: gb-2004-5-4-217, DOI: 10.1186/gb-2004-5-4-217, ISSN: 1474-760X.

Subramanian C, Xu Y, Johnson CH, von Arnim AG. In vivo detection of protein-protein interaction in plant cells using BRET. Methods Mol. Biol. 2004; 284: 271-86. PMID: 15173623, PII: 1-59259-816-1:271, DOI: 10.1385/1-59259-816-1:271, ISSN: 1064-3745.

Johnson, C.H. and M. Egli. Visualizing a biological clockwork's cogs. Nature Structural and Molecular Biology. 2004; 11((7)): 584-5.

Johnson, C.H.. As time glows by in bacteria. Nature. 2004; 430((1)): 23-4.

Izumo M, Johnson CH, Yamazaki S. Circadian gene expression in mammalian fibroblasts revealed by real-time luminescence reporting: temperature compensation and damping. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Dec 12/23/2003; 100(26): 16089-94. PMID: 14657355, PMCID: PMC307697, PII: 2536313100, DOI: 10.1073/pnas.2536313100, ISSN: 0027-8424.

Johnson CH, Elliott JA, Foster R. Entrainment of circadian programs. Chronobiol. Int. 2003 Sep; 20(5): 741-74. PMID: 14535352, ISSN: 0742-0528.

Schoenhard JA, Smith LH, Painter CA, Eren M, Johnson CH, Vaughan DE. Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. J. Mol. Cell. Cardiol. 2003 May; 35(5): 473-81. PMID: 12738229, PII: S0022282803000518, ISSN: 0022-2828.

Xu Y, Mori T, Johnson CH. Cyanobacterial circadian clockwork: roles of KaiA, KaiB and the kaiBC promoter in regulating KaiC. EMBO J. 2003 May 5/1/2003; 22(9): 2117-26. PMID: 12727878, PMCID: PMC156062, DOI: 10.1093/emboj/cdg168, ISSN: 0261-4189.

Xu Y, Kanauchi A, von Arnim AG, Piston DW, Johnson CH. Bioluminescence resonance energy transfer: monitoring protein-protein interactions in living cells. Meth. Enzymol. 2003; 360: 289-301. PMID: 12622156, ISSN: 0076-6879.

Hastings JW, Johnson CH. Bioluminescence and chemiluminescence. Meth. Enzymol. 2003; 360: 75-104. PMID: 12622147, ISSN: 0076-6879.

Mori T, Saveliev SV, Xu Y, Stafford WF, Cox MM, Inman RB, Johnson CH. Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Dec 12/24/2002; 99(26): 17203-8. PMID: 12477935, PMCID: PMC139293, PII: 262578499, DOI: 10.1073/pnas.262578499, ISSN: 0027-8424.

Schoenhard JA, Eren M, Johnson CH, Vaughan DE. Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization. Am. J. Physiol., Cell Physiol. 2002 Jul; 283(1): C103-14. PMID: 12055078, DOI: 10.1152/ajpcell.00541.2001, ISSN: 0363-6143.

Sai J, Johnson CH. Dark-stimulated calcium ion fluxes in the chloroplast stroma and cytosol. Plant Cell. 2002 Jun; 14(6): 1279-91. PMID: 12084827, PMCID: PMC150780, ISSN: 1040-4651.

Suzuki L, Johnson CH. Photoperiodic control of germination in the unicell Chlamydomonas. Naturwissenschaften. 2002 May; 89(5): 214-20. PMID: 12135086, ISSN: 0028-1042.

Xu Y, Johnson CH, Piston D. Bioluminescence resonance energy transfer assays for protein-protein interactions in living cells. Methods Mol. Biol. 2002; 183: 121-33. PMID: 12136748, PII: 1-59259-280-5-121, DOI: 10.1385/1-59259-280-5:121, ISSN: 1064-3745.

Mori T, Johnson CH. Circadian programming in cyanobacteria. Semin. Cell Dev. Biol. 2001 Aug; 12(4): 271-8. PMID: 11463211, PII: S1084-9521(01)90254-X, DOI: 10.1006/scdb.2001.0254, ISSN: 1084-9521.

Xu Y, Johnson CH. A clock- and light-regulated gene that links the circadian oscillator to LHCB gene expression. Plant Cell. 2001 Jun; 13(6): 1411-25. PMID: 11402169, PMCID: PMC135572, ISSN: 1040-4651.

Mori T, Johnson CH. Independence of circadian timing from cell division in cyanobacteria. J. Bacteriol. 2001 Apr; 183(8): 2439-44. PMID: 11274102, PMCID: PMC95159, DOI: 10.1128/JB.183.8.2439-2444.2001, ISSN: 0021-9193.

Johnson CH. Endogenous timekeepers in photosynthetic organisms. Annu. Rev. Physiol. 2001; 63: 695-728. PMID: 11181973, PII: 63/1/695, DOI: 10.1146/annurev.physiol.63.1.695, ISSN: 0066-4278.

Dassarma S, Kennedy SP, Berquist B, Victor Ng W, Baliga NS, Spudich JL, Krebs MP, Eisen JA, Johnson CH, Hood L. Genomic perspective on the photobiology of Halobacterium species NRC-1, a phototrophic, phototactic, and UV-tolerant haloarchaeon. Photosyn. Res. 2001; 70(1): 3-17. PMID: 16228359, DOI: 10.1023/A:1013879706863, ISSN: 1573-5079.

Xu Y, Mori T, Johnson CH. Circadian clock-protein expression in cyanobacteria: rhythms and phase setting. EMBO J. 2000 Jul 7/3/2000; 19(13): 3349-57. PMID: 10880447, PMCID: PMC313937, DOI: 10.1093/emboj/19.13.3349, ISSN: 0261-4189.

Nikaido SS, Johnson CH. Daily and circadian variation in survival from ultraviolet radiation in Chlamydomonas reinhardtii. Photochem. Photobiol. 2000 Jun; 71(6): 758-65. PMID: 10857373, ISSN: 0031-8655.

Mori T, Johnson CH. Circadian control of cell division in unicellular organisms. Prog Cell Cycle Res. 2000; 4: 185-92. PMID: 10740825, ISSN: 1087-2957.

Johnson CH. Forty years of PRCs--what have we learned?. Chronobiol. Int. 1999 Nov; 16(6): 711-43. PMID: 10584173, ISSN: 0742-0528.

Sai J, Johnson CH. Different circadian oscillators control Ca(2+) fluxes and lhcb gene expression. Proc. Natl. Acad. Sci. U.S.A. 1999 Sep 9/28/1999; 96(20): 11659-63. PMID: 10500233, PMCID: PMC18090, ISSN: 0027-8424.

Xu Y, Piston DW, Johnson CH. A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proc. Natl. Acad. Sci. U.S.A. 1999 Jan 1/5/1999; 96(1): 151-6. PMID: 9874787, PMCID: PMC15108, ISSN: 0027-8424.

Johnson CH, Golden SS. Circadian programs in cyanobacteria: adaptiveness and mechanism. Annu. Rev. Microbiol. 1999; 53: 389-409. PMID: 10547696, DOI: 10.1146/annurev.micro.53.1.389, ISSN: 0066-4227.

Golden SS, Johnson CH, Kondo T. The cyanobacterial circadian system: a clock apart. Curr. Opin. Microbiol. 1998 Dec; 1(6): 669-73. PMID: 10066545, PII: S1369-5274(98)80113-6, ISSN: 1369-5274.

Johnson CH, Golden SS, Kondo T. Adaptive significance of circadian programs in cyanobacteria. Trends Microbiol. 1998 Oct; 6(10): 407-10. PMID: 9807785, PII: S0966-842X(98)01356-0, ISSN: 0966-842X.

Ishiura M, Kutsuna S, Aoki S, Iwasaki H, Andersson CR, Tanabe A, Golden SS, Johnson CH, Kondo T. Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria. Science. 1998 Sep 9/4/1998; 281(5382): 1519-23. PMID: 9727980, ISSN: 0036-8075.

Ouyang Y, Andersson CR, Kondo T, Golden SS, Johnson CH. Resonating circadian clocks enhance fitness in cyanobacteria. Proc. Natl. Acad. Sci. U.S.A. 1998 Jul 7/21/1998; 95(15): 8660-4. PMID: 9671734, PMCID: PMC21132, ISSN: 0027-8424.

Golden SS, Ishiura M, Johnson CH, Kondo T. CYANOBACTERIAL CIRCADIAN RHYTHMS. Annu. Rev. Plant Physiol. Plant Mol. Biol. 1997 Jun; 48: 327-54. PMID: 15012266, DOI: 10.1146/annurev.arplant.48.1.327, ISSN: 1040-2519.

Mori T, Binder B, Johnson CH. Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours. Proc. Natl. Acad. Sci. U.S.A. 1996 Sep 9/17/1996; 93(19): 10183-8. PMID: 8816773, PMCID: PMC38358, ISSN: 0027-8424.

Jacobshagen S, Kindle KL, Johnson CH. Transcription of CABII is regulated by the biological clock in Chlamydomonas reinhardtii. Plant Mol. Biol. 1996 Sep; 31(6): 1173-84. PMID: 8914533, ISSN: 0167-4412.

Johnson CH, Golden SS, Ishiura M, Kondo T. Circadian clocks in prokaryotes. Mol. Microbiol. 1996 Jul; 21(1): 5-11. PMID: 8843429, ISSN: 0950-382X.

Liu Y, Tsinoremas NF, Golden SS, Kondo T, Johnson CH. Circadian expression of genes involved in the purine biosynthetic pathway of the cyanobacterium Synechococcus sp. strain PCC 7942. Mol. Microbiol. 1996 Jun; 20(5): 1071-81. PMID: 8809759, ISSN: 0950-382X.

Tsinoremas NF, Ishiura M, Kondo T, Andersson CR, Tanaka K, Takahashi H, Johnson CH, Golden SS. A sigma factor that modifies the circadian expression of a subset of genes in cyanobacteria. EMBO J. 1996 May 5/15/1996; 15(10): 2488-95. PMID: 8665856, PMCID: PMC450181, ISSN: 0261-4189.

Johnson CH, Knight MR, Kondo T, Masson P, Sedbrook J, Haley A, Trewavas A. Circadian oscillations of cytosolic and chloroplastic free calcium in plants. Science. 1995 Sep 9/29/1995; 269(5232): 1863-5. PMID: 7569925, ISSN: 0036-8075.

Liu Y, Tsinoremas NF, Johnson CH, Lebedeva NV, Golden SS, Ishiura M, Kondo T. Circadian orchestration of gene expression in cyanobacteria. Genes Dev. 1995 Jun 6/15/1995; 9(12): 1469-78. PMID: 7601351, ISSN: 0890-9369.

Goto K, Johnson CH. Is the cell division cycle gated by a circadian clock? The case of Chlamydomonas reinhardtii. J. Cell Biol. 1995 May; 129(4): 1061-9. PMID: 7744955, PMCID: PMC2120501, ISSN: 0021-9525.

Liu Y, Golden SS, Kondo T, Ishiura M, Johnson CH. Bacterial luciferase as a reporter of circadian gene expression in cyanobacteria. J. Bacteriol. 1995 Apr; 177(8): 2080-6. PMID: 7536731, PMCID: PMC176852, ISSN: 0021-9193.

Johnson CH, Nakaoka Y, Miwa I. The effects of altering extracellular potassium ion concentration on the membrane potential and circadian clock of Paramecium bursaria. J. Exp. Biol. 1994 Dec; 197: 295-308. PMID: 7852906, ISSN: 0022-0949.

Kondo T, Tsinoremas NF, Golden SS, Johnson CH, Kutsuna S, Ishiura M. Circadian clock mutants of cyanobacteria. Science. 1994 Nov 11/18/1994; 266(5188): 1233-6. PMID: 7973706, ISSN: 0036-8075.

Johnson CH. Illuminating the clock: circadian photobiology. Semin. Cell Biol. 1994 Oct; 5(5): 355-62. PMID: 7881075, ISSN: 1043-4682.

Jacobshagen S, Johnson CH. Circadian rhythms of gene expression in Chlamydomonas reinhardtii: circadian cycling of mRNA abundances of cab II, and possibly of beta-tubulin and cytochrome c. Eur. J. Cell Biol. 1994 Jun; 64(1): 142-52. PMID: 7957302, ISSN: 0171-9335.

Kondo T, Strayer CA, Kulkarni RD, Taylor W, Ishiura M, Golden SS, Johnson CH. Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc. Natl. Acad. Sci. U.S.A. 1993 Jun 6/15/1993; 90(12): 5672-6. PMID: 8516317, PMCID: PMC46783, ISSN: 0027-8424.

Johnson CH, Kondo T. Light pulses induce "singular" behavior and shorten the period of the circadian phototaxis rhythm in the CW15 strain of Chlamydomonas. J. Biol. Rhythms. 1992; 7(4): 313-27. PMID: 1286203, ISSN: 0748-7304.

Johnson CH, Kondo T, Hastings JW. Action Spectrum for Resetting the Circadian Phototaxis Rhythm in the CW15 Strain of Chlamydomonas: II. Illuminated Cells. Plant Physiol. 1991 Nov; 97(3): 1122-9. PMID: 16668498, PMCID: PMC1081131, ISSN: 0032-0889.

Kondo T, Johnson CH, Hastings JW. Action Spectrum for Resetting the Circadian Phototaxis Rhythm in the CW15 Strain of Chlamydomonas: I. Cells in Darkness. Plant Physiol. 1991 Jan; 95(1): 197-205. PMID: 16667951, PMCID: PMC1077506, ISSN: 0032-0889.

Johnson CH, Nakashima H. Cycloheximide inhibits light-induced phase shifting of the circadian clock in Neurospora. J. Biol. Rhythms. 1990; 5(2): 159-67. PMID: 2133125, ISSN: 0748-7304.

Johnson CH, Hastings JW. Circadian phototransduction: phase resetting and frequency of the circadian clock of Gonyaulax cells in red light. J. Biol. Rhythms. 1989; 4(4): 417-37. PMID: 2519604, ISSN: 0748-7304.

Johnson CH, Miwa I, Kondo T, Hastings JW. Circadian rhythm of photoaccumulation in Paramecium bursaria. J. Biol. Rhythms. 1989; 4(4): 405-15. PMID: 2519603, ISSN: 0748-7304.

Broda H, Johnson CH, Taylor WR, Hastings JW. Temperature dependence of phase response curves for drug-induced phase shifts. J. Biol. Rhythms. 1989; 4(3): 327-33. PMID: 2519597, ISSN: 0748-7304.

Nicolas MT, Nicolas G, Johnson CH, Bassot JM, Hastings JW. Characterization of the bioluminescent organelles in Gonyaulax polyedra (dinoflagellates) after fast-freeze fixation and antiluciferase immunogold staining. J. Cell Biol. 1987 Aug; 105(2): 723-35. PMID: 2442172, PMCID: PMC2114768, ISSN: 0021-9525.

Olesiak W, Ungar A, Johnson CH, Hastings JW. Are protein synthesis inhibition and phase shifting of the circadian clock in Gonyaulax correlated?. J. Biol. Rhythms. 1987; 2(2): 121-38. PMID: 2979654, ISSN: 0748-7304.

Nicolas MT, Johnson CH, Bassot JM, Hastings JW. Immunogold labeling of organelles in the bioluminescent dinoflagellate Gonyaulax polyedra with anti-luciferase antibody. Cell Biol. Int. Rep. 1985 Sep; 9(9): 797-802. PMID: 3899376, ISSN: 0309-1651.

Johnson CH, Inoué S, Flint A, Hastings JW. Compartmentalization of algal bioluminescence: autofluorescence of bioluminescent particles in the dinoflagellate Gonyaulax as studied with image-intensified video microscopy and flow cytometry. J. Cell Biol. 1985 May; 100(5): 1435-46. PMID: 4039325, PMCID: PMC2113859, ISSN: 0021-9525.

Available Postdoctoral Position Details
Posted: 8/23/2014
One Postdoctoral Position is available October 1, 2014:

Innovative Luminescence Assay for Neural Activity, [Ca++], and pH: My laboratory has developed innovative techniques using luminescence and/or BRET (Bioluminescence Resonance Energy Transfer) to monitor gene expression or protein-protein interactions non-invasively. These luminescence techniques have significant advantages over fluorescence-based (and other) methodologies. We have extensively developed luminescence techniques for monitoring circadian gene expression patterns as well as assessing interactions among proteins in mammalian, plant, and bacterial cells. We have developed a luminescence reporter for pH and comparable reporters for [Ca++] are under development. The current position is to further develop these state-of-the art techniques and apply them as non-invasive monitors of neural synaptic activity. Useful reporters will be applied to answer fundamental neurobiological questions (including those relating to circadian rhythmicity) in conjunction with optogenetics. Experience with neurobiology, imaging, and standard molecular genetic techniques is desirable.

There are excellent facilities and collaborations available within the Vanderbilt University system, including other laboratories that study circadian clocks & sleep (e.g., the labs of Doug McMahon, Terry Page, and Beth Malow) and/or that are developing advanced imaging techniques (e.g., David Piston). Nashville is an exciting city with a low cost of living and many artistic opportunities (especially music) as well as close proximity to nature. For more information about my laboratory, see our website: Interested applicants should contact Dr. Carl Johnson at: