Carl H. Johnson

Carl H. Johnson
Born Washington, D.C
Residence Nashville, Tennessee
Nationality United States
Fields Biology, Circadian rhythm
Institutions Vanderbilt University
Alma mater University of Texas at Austin
Stanford University
Harvard University
Doctoral advisor David Epel
Colin Pittendrigh
Other academic advisors Michael Menaker

Carl Hirschie Johnson is an American-born biologist who researches the chronobiology of different organisms, most notably the bacterial circadian rhythms of cyanobacteria.[1] Johnson completed his undergraduate degree in Honors Liberal Arts at the University of Texas at Austin, and later earned his PhD in biology from Stanford University, where he began his research under the mentorship of Dr. Colin Pittendrigh.[2] Currently, Johnson is the Stevenson Professor of Biological Sciences at Vanderbilt University.[3]

Personal life

Carl Johnson was born in Washington D.C. When he first began college at the University of Texas at Austin, he planned to go to medical school rather than pursue research.[2] However, he quickly developed a passion for research after working as an undergraduate student in a chronobiology lab directed by Dr. Michael Menaker. Johnson asserts that “music led [him] to science,” as he originally began his research job with Menaker to pay for classical voice lessons. Classical music has remained a major avocation, as he continues to sing music with the chorus of the Nashville Symphony Orchestra.[4] Also in his free time, he enjoys yoga.[2]

Scientific career

Early Career and Education

Johnson graduated with a B.A. in Honors Liberal Arts (the Plan II Honors program [5]) at the University of Texas at Austin in 1976. During this time, he became involved in undergraduate research under the mentorship of Dr. Michael Menaker, whose lab was studying biological clocks in birds and rodents.[6][7][8] Johnson’s exposure to the practice of experimental research in Dr. Menaker’s lab inspired him to go to graduate school instead of following his original plan to become a physician.[2] He went on to earn his Ph.D. in Biology in 1982 at Stanford University, first working under the renowned leader in chronobiology, Colin Pittendrigh and then moving to David Epel’s laboratory to finish his degree. Subsequently, Johnson conducted postdoctoral work in Cell & Developmental Biology at Harvard University, which he completed in 1987, with Dr. J.W. ‘Woody’ Hastings (John Woodland Hastings), a biologist famous for his work on bioluminescence in many organisms, including algae.[9] Hastings became a close friend and mentor to Johnson. In 1987, Johnson came to Vanderbilt University to initiate an independent research program, and he has been a biology professor at Vanderbilt since then.[2][3]

Research Beginnings

Johnson’s initial foray into research was as an undergraduate in Menaker’s lab, which was working on the pineal gland in birds[7][10] and other chronobiology projects in vertebrates.[8] In graduate school at Stanford under Colin Pittendrigh, Johnson attempted to discover circadian rhythms in a variety of organism such as leeches and cockroaches. He also worked with earthworms to see whether they would completely recover circadian rhythms upon regeneration of lesioned parts of their brains. He also developed a method to measure the pH levels inside cells in search of rhythmic acid/base relationships. However only one of these projects ultimately resulted in a publication, namely a paper about the clock’s control over the pH in the bread mould Neurospora crassa.[11] Johnson switched to David Epel’s marine biology lab [12] in his fourth year of graduate school, because their work on the pH change in sea urchin and starfish eggs upon fertilization was an excellent system in which to apply the method he had developed earlier to measure the pH levels inside cells.[13][14] He successfully published a number of papers on this topic.[15][16] In his postdoctoral studies with Hastings, Johnson returned to the biological clocks field and worked mainly on rhythms in the bioluminescent alga Gonyaulax polyedra [17][18] and later in the algal model system for genetics, Chlamydomonas reinhardtii.[19]

Major contributions

Circadian System in Cyanobacteria

Prior to the late 1980s, most chronobiologists believed that bacteria were too "simple" to express circadian rhythms.[20] Johnson did not accept this dogma, and as early as 1978, he was examining haloarchaea for the possible presence of biological clocks. While the studies of haloarchaea were not productive, when other studies suggested the possibility of circadian rhythms in cyanobacteria,[21][22] Johnson along with colleagues and collaborators used a luciferase reporter system to prove that Synechococcus elongatus, of the phylum cyanobacteria, showed evidence of daily bacterial circadian rhythms (with circa-24 hour cycles).[23] Synechococcus expressed free-running rhythms, temperature compensation, and ability to entrain, which are the defining properties of circadian rhythms.[1] These organisms also regulate cell division with forbidden and allowed phases.[24] Therefore, Johnson and coworkers challenged the original belief that bacteria do not have daily biological cycles. Moreover, they identified the central elements of the bacterial clock, namely the KaiABC gene cluster, and determined their structure.[25] Currently, the idea that bacterial circadian rhythms exist in at least some prokaryotes is well accepted by the chronobiology community, and prokaryotes are an important model system for studying rhythmicity.

Bioluminescence Resonance Energy Transfer (BRET)

In 1999, Johnson and his team developed and patented a new method of studying the interaction of molecules based on Förster resonance energy transfer (FRET), also known as Fluorescent Resonance Energy Transfer (FRET).[26] They modified the existing technique of FRET so that instead of using light to activate fluorophores attached to the proteins of interest, they employed bioluminescent proteins with luciferase activity. BRET eliminates the need for light excitation and so avoids changes that light generally causes in circadian clocks, such as resetting the clock phase. Because it avoids light excitation (as in the case of FRET), BRET can also be helpful (1) when tissues are autofluorescent, (2) when light excitation causes phototoxicity, photoresponses (as in retina), or photobleaching, and (3) in partnership with optogenetics.[27] This new method for measuring protein-protein interactions gives researchers the ability to develop novel reporters for intracellular calcium and hydrogen ions. This method is projected to be extremely useful for researchers dealing with live cell cultures, cell extracts and purified proteins.

Current Work

The Johnson Lab is currently applying biophysical methods to explain how the central bacterial clock proteins (KaiA + KaiB + KaiC) oscillate in vitro.[28][29] Together with the laboratory of Dr. Martin Egli, Dr. Johnson’s lab has led a concerted effort to apply structural biology techniques for insight into circadian clock mechanisms.[25][30] The lab has also used mutants and codon bias in cyanobacteria to provide the first rigorous evidence for the adaptive significance of biological clocks in fitness.[31][32][33] The Johnson lab is expanding the study of bacterial circadian rhythms from cyanobacteria to purple bacteria.[34] Currently the lab is also conducting studies on the circadian system of mammals in vivo and in vitro, by using luminescence as a tool to monitor circadian rhythms in the brain.[27] Finally, Johnson and his lab is studying circadian and sleep phenotypes of mouse models of the serious human neurodevelopmental disorder called Angelman Syndrome. The lab hopes to find chronotherapeutic ways to ameliorate the sleep disorders of patients suffering from this syndrome.[35]

Timeline of accomplishments

Positions and honors

See also

References

  1. 1 2 Johnson, C.H. “From Skepticism to Prominence: Circadian Clocks in Bacteria”. Microbe 4(9). Sept, 2009
  2. 1 2 3 4 5 "Carl Hirschie Johnson." Current Biology, vol. 24, no. 3, 2014, pp. R100-R102.
  3. 1 2 “Department of Biological Sciences - Carl H. Johnson”. Vanderbilt University. http://as.vanderbilt.edu/biosci/bio/carl-johnson. Accessed 29 Nov, 2016.
  4. ↑ “Nashville Symphony Chorus Roster”. https://www.nashvillesymphony.org/about/chorus/roster. Accessed 29 Nov, 2016.
  5. ↑ Plan II Honors Program, University of Texas at Austin. https://liberalarts.utexas.edu/plan2/. Accessed 29 Nov, 2016.
  6. ↑ Michael Menaker. University of Virginia College and Graduate School of Arts & Sciences, 2015, bio.as.virginia.edu/people/mm7e. Accessed 29 Nov. 2016.
  7. 1 2 Gaston, S, and M. Menaker. 1968. Pineal function: the biological clock in the sparrow? Science 160(3832): 1125-1127.
  8. 1 2 Stetson, M. H., Elliott J.A., and M. Menaker. 1975. Photoperiodic regulation of Hamster testis: circadian sensitivity to the effects of light. Biology of Reproduction 13: 329-339.
  9. ↑ Hastings Lab Home Page. Harvard University Biological Laboratories, Sept. 2006, labs.mcb.harvard.edu/hastings/dino.html. Accessed 29 Nov. 2016.
  10. ↑ Takahashi, J. S., Hamm H., and M. Menaker. 1980. Circadian rhythms of melatonin release from individual superfused chicken pineal glands in vitro. Proc. Natl. Acad. Sci. USA 77: 2319-2322.
  11. ↑ Johnson, C. H. 1983. Changes of intracellular pH are not correlated with the circadian rhythm of Neurospora. Plant Physiol. 72: 129-133.
  12. ↑ David Epel. Stanford University Hopkins Marine Station, http://hopkinsmarinestation.stanford.edu/people/david-epel. Accessed 29 November 2016.
  13. ↑ Johnson, C. H., and D. Epel. 1981. Intracellular pH of sea urchin eggs measured by the dimethyloxazolidinedione (DMO) method. J. Cell Biology 89: 284-291.
  14. ↑ Johnson, C. H., and D. Epel. 1982. Starfish oocyte maturation and fertilization: intracellular pH is not involved in activation. Devel. Biol. 92: 461-469.
  15. ↑ Johnson, C. H., and D. Epel. 1983. Heavy metal chelators prolong motility and viability of sea urchin sperm by inhibiting spontaneous acrosome reactions. J. Exp. Zool. 226: 431-440.
  16. ↑ Johnson, C. H., D. L. Clapper, M. W. Winkler, H. C. Lee, and D. Epel. 1983. A volatile inhibitor immobilizes sea urchin sperm in semen by depressing the intracellular pH. Devel. Biol. 98: 493-501.
  17. ↑ Johnson, C. H., J. F. Roeber, and J. W. Hastings. 1984. Circadian changes of enzyme concentration account for rhythm of enzyme activity in Gonyaulax. Science 223: 1428-1430.
  18. ↑ Johnson, C. H., and J. W. Hastings. 1989. Circadian phototransduction: phase-resetting and frequency of the circadian clock of Gonyaulax cells in red light. J. Biol. Rhythms 4: 417-437.
  19. ↑ Johnson, C. H., T. Kondo, and J. W. Hastings. 1991. Action spectrum for resetting the circadian phototaxis rhythm in the CW15 strain of Chlamydomonas. II. Illuminated cells. Plant Physiol. 97: 1122-1129.
  20. ↑ Johnson, C.H., S.S. Golden, M. Ishiura, and T. Kondo. 1996. Circadian clocks in prokaryotes. Mole. Microbiol. 21: 5-11. PMID 8843429
  21. ↑ Huang T-C and Grobbelaar N (1995) The circadian clock in the prokaryote Synechococcus RF-1. Microbiology 141: 535–540.
  22. ↑ Sweeney BM, and Borgese MB (1989) A circadian rhythm in cell division in a prokaryote, the cyanobacterium Synechococcus WH7803. J. Phycol. 25: 183–186
  23. ↑ Kondo, T., C. A. Strayer, R. D. Kulkarni, W. Taylor, M. Ishiura, S. S. Golden, and C. H. Johnson. 1993. Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc. Natl. Acad. Sci. USA 90: 5672-5676. PMC 46783
  24. ↑ Mori, T., B. Binder, and C.H. Johnson. 1996. Circadian gating of cell division in cyanobacteria growing with average doubling times of less than 24 hours. Proc. Natl. Acad. Sci. USA 93: 10183-10188. PMC 38358
  25. 1 2 Pattanayek, R., J. Wang, T. Mori, Y. Xu, C.H. Johnson, and M. Egli. 2004. Visualizing a circadian clock protein: crystal structure of KaiC and functional insights. Molecular Cell 15: 375–388. PMID 15304218 doi:10.1016/j.molcel.2004.07.013
  26. ↑ Xu, Y., Piston, D. W., & Johnson, C. H. (1999). A bioluminescence resonance energy transfer (BRET) system: application to interacting circadian clock proteins. Proceedings of the National Academy of Sciences, 96(1), 151-156. PMC 15108
  27. 1 2 Yang, J., D. Cumberbatch, S. Centanni, S. Shi, D. Winder, D. Webb, C.H. Johnson. 2016. Coupling Optogenetic Stimulation with NanoLuc-based Luminescence (BRET) Ca ++ Sensing. Nature Communications 7: 13268. doi:10.1038/ncomms13268
  28. ↑ Johnson, C. H., and M. Egli. 2014. Metabolic compensation and circadian resilience in prokaryotic cyanobacteria. Annu. Rev. Biochem. 83: 221-47. PMID 24905782 PMC 4259047 doi:10.1146/annurev-biochem-060713-035632
  29. ↑ Mori, T., D.R. Williams, M.O. Byrne, X. Qin, H.S. Mchaourab, M. Egli, P.L. Stewart, and C.H. Johnson. 2007. Elucidating the Ticking of an in vitro Circadian Clockwork.PLoS Biology 5: e93. PMID 17388688 PMC 1831719 doi:10.1371/journal.pbio.0050093
  30. ↑ Johnson, C.H., M. Egli, P.L. Stewart. 2008. Structural Insights into a Circadian Oscillator. Science 322: 697-701. PMID 18974343 PMC 2588432 doi:10.1126/science.1150451
  31. ↑ Ouyang, Y., C.R. Andersson, T. Kondo, S.S. Golden, and C.H. Johnson. 1998. Resonating circadian clocks enhance fitness in cyanobacteria. Proc. Natl. Acad. Sci. USA 95: 8660-8664.
  32. ↑ Xu, Y., P. Ma, P. Shah, A. Rokas, Y. Liu, C.H. Johnson. 2013. Non-optimal codon usage is a mechanism to achieve circadian clock conditionality. Nature 495: 116-20. doi:10.1038/nature11942
  33. ↑ Woelfle, M.A., Y. Ouyang, K. Phanvijhitsiri, and C.H. Johnson.2004. The adaptive value of circadian clocks: An experimental assessment in cyanobacteria. Current Biology 14: 1481–1486. PMID 15324665 doi:10.1016/j.cub.2004.08.023
  34. ↑ Ma, P., T. Mori, C. Zhao, T. Thiel, C.H. Johnson. 2016. Evolution of KaiC-dependent timekeepers: a proto-circadian timing mechanism confers adaptive fitness in the purple bacterium Rhodopseudomonas palustris. PLoS Genetics 12: e1005922. doi:10.1371/journal.pgen.1005922
  35. ↑ Shi, S., T.J. Bichell, R.A. Ihrie, C.H. Johnson. 2015. Ube3a Imprinting Impairs Circadian Robustness in Angelman Syndrome Models. Current Biology 25: 537–545. doi:10.1016/j.cub.2014.12.047
  36. ↑ http://srbr.org/meetings/previous-meetings/
  37. ↑ http://www.vanderbilt.edu/provost/faculty-highlights/chancellors-research.php
  38. ↑ aschoff-honma.wixsite.com/ahmf/prize-winners
  39. ↑ https://my.vanderbilt.edu/phibetakappa/about-the-chapter/
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