Johan Paulsson

Last updated
Johan Paulsson
Born
Kristinehamn, Sweden
Citizenship Sweden
Alma mater Uppsala University (M.S., Ph.D.)
Scientific career
Fields Systems biology, Mathematical biology, Stochastic Process
Institutions Harvard

Johan Paulsson is a Swedish mathematician and systems biologist at Harvard Medical School. He is a leading researcher in systems biology and stochastic processes, specializing in stochasticity in gene networks and plasmid reproduction.

Contents

Biography

Johan Paulsson was born in 1973, in Kristinehamn, a small city in the Swedish province of Värmland. He studied at Uppsala University, where he obtained a BSc in Mathematics in 1996, a Masters of Science in Molecular Biology in 1996, and a Ph.D. in Molecular Biology in 2000 on stochasticity in intracellular circuits, in particular in plasmid copy control, under the supervision of Profs. Mans Ehrenberg and Kurt Nordström. In 2000 he moved to Princeton University, where he was a Lewis-Thomas Fellow in Biophysics, where he did the research for his paper "Summing up the noise in genetic networks", which received wide attention because it gave a firm theoretical footing to the budding field of genetic noise. In 2003 he joined the Dept. of Applied Mathematics and Theoretical Physics at the University of Cambridge and was tenured the following year. In 2005 he moved to the recently created Department of Systems Biology at Harvard University, where he focused on the development of experimental techniques for counting plasmids in single cells and on theoretical results on control of fluctuations in gene expression.

He is married with two children.

Work

Paulsson's lab has made major contributions to the development of experimental techniques for counting plasmids, to extend his previous work on the mathematical aspects of plasmid replication [1] [2] [3] [4] [5] as well as theoretical work on the stochastic processes on gene expression and copy number control [6] [7] [8] [9] [10] and work on muti-level selection [11] by using experimental evolution.

His most influential publication is the analysis of all previous noise data and interpretations in one unified framework, [12] [13] which later guided many experimental approaches. [14] [15] [16]

More recent results include the effects of partition in phenotypic variability, [17] the details of the stochastic processes that underlie gene expression noise and the limitations of the usual experimental approaches [18] [19] and the fundamental limits of feedback as a noise control mechanism. [20] This set of interests led Paulsson to examine the repressilator, a synthetic gene regulatory network that was designed from scratch to oscillate and reported in 2000 [21] by Michael Elowitz and Stanislas Leibler. Although the repressilator oscillated, and therefore demonstrated the potential of synthetic biology, the oscillations were noisy and quickly became incoherent on the single cell level. Using an understanding of the causes of noise in cellular networks, Paulsson's team was able to redesign the repressilator, retaining the basic design, to produce a new synthetic circuit that oscillated with unprecedented accuracy [22]

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References

  1. ↑ Paulsson, J; K. Nordström; and M.Ehrenberg (1998). "Requirements for rapid plasmid copy number adjustments". Plasmid. 39 (3): 215–234. doi:10.1006/plas.1998.1338. PMID   9571138.
  2. ↑ Paulsson, J; M.Ehrenberg (1998). "Trade-off between segregational stability and metabolic burden". J. Mol. Biol. 279 (1): 73–88. doi:10.1006/jmbi.1998.1751. PMID   9636701.
  3. ↑ Paulsson, J; M.Ehrenberg (2000). "Molecular clocks reduce plasmid losses: the R1 case". J. Mol. Biol. 297 (1): 179–92. doi:10.1006/jmbi.2000.3526. PMID   10704315.
  4. ↑ Paulsson, J; M.Ehrenberg (2000). "Random signal fluctuations can reduce random fluctuations in regulated components of chemical regulatory networks". Phys. Rev. Lett. 84 (23): 5447–50. Bibcode:2000PhRvL..84.5447P. doi:10.1103/PhysRevLett.84.5447. PMID   10990965.
  5. ↑ Park, K.; E. Han; J. Paulsson; D. K. Chattoraj (2001). "Origin pairing ('handcuffing') as a mode of negative control of P1 plasmid copy number". EMBO J. 20 (24): 7323–32. doi:10.1093/emboj/20.24.7323. PMC   125786 . PMID   11743008.
  6. ↑ Paulsson, J; O. G. Berg; M. Ehrenberg (2000). "Stochastic Focusing: Fluctuation enhanced sensitivity of intracellular regulation". Proc. Natl. Acad. Sci. U.S.A. 97 (13): 7148–53. Bibcode:2000PNAS...97.7148P. doi: 10.1073/pnas.110057697 . PMC   16514 . PMID   10852944.
  7. ↑ Berg, O. G.; J. Paulsson; M. Ehrenberg (2000). "Fluctuations and quality of control in biological cells – Zero order ultrasensitivity reinvestigated". Biophys. J. 79 (3): 1228–36. Bibcode:2000BpJ....79.1228B. doi:10.1016/S0006-3495(00)76377-6. PMC   1301019 . PMID   10968987.
  8. ↑ Berg, O. G.; J. Paulsson; M. Ehrenberg (2000). "Fluctuations in repressor control: Thermodynamic constraints on Stochastic Focusing". Biophys. J. 79 (6): 2944–53. Bibcode:2000BpJ....79.2944B. doi:10.1016/S0006-3495(00)76531-3. PMC   1301173 . PMID   11106602.
  9. ↑ Paulsson, J; M.Ehrenberg (2001). "Noise in a minimal regulatory network: plasmid copy number control". Q. Rev. Biophys. 34 (1): 1–59. CiteSeerX   10.1.1.583.8757 . doi:10.1017/s0033583501003663. PMID   11388089. S2CID   31387524.
  10. ↑ Elf, J.; J. Paulsson; O. G. Berg; M. Ehrenberg (2003). "Near-critical phenomena in intracellular metabolite pools". Biophys. J. 84 (1): 154–70. Bibcode:2003BpJ....84..154E. doi:10.1016/S0006-3495(03)74839-5. PMC   1302600 . PMID   12524272.
  11. ↑ Paulsson, J (2002). "Noise in a minimal regulatory network: plasmid copy number control". Genetics. 161 (4): 1373–84. doi:10.1093/genetics/161.4.1373. PMC   1462198 . PMID   12238464.
  12. ↑ Paulsson, J (2004). "Summing up the noise in gene networks". Nature. 427 (6973): 415–8. Bibcode:2004Natur.427..415P. doi:10.1038/nature02257. PMID   14749823. S2CID   4355591.
  13. ↑ Paulsson, J (2005). "Models of Stochastic Gene Expression". Phys. Life Rev. 2 (2): 157–175. Bibcode:2005PhLRv...2..157P. doi:10.1016/j.plrev.2005.03.003.
  14. ↑ Golding, I; Paulsson J; Zawilski SM; Cox EC. (2005). "Real-time kinetics of gene activity in individual bacteria". Cell. 123 (6): 1025–36. doi: 10.1016/j.cell.2005.09.031 . PMID   16360033. S2CID   10319035.
  15. ↑ Bar-Even, A; Paulsson J; Maheshri N; Carmi M; O'Shea E; Pilpel Y; Barkai N. (2006). "Noise in protein expression scales with natural protein abundance". Nat. Genet. 38 (6): 636–43. doi:10.1038/ng1807. PMID   16715097. S2CID   9276506.
  16. ↑ Rando, O J; J. Paulsson (2006). "Noisy silencing of chromatin". Cell. 11 (2): 134–6. doi: 10.1016/j.devcel.2006.07.012 . PMID   16890152.
  17. ↑ Huh, D; J. Paulsson (2011). "Non-genetic heterogeneity from stochastic partitioning at cell division". Nat. Genet. 43 (2): 95–100. doi:10.1038/ng.729. PMC   3208402 . PMID   21186354.
  18. ↑ Pedraza, J M; J. Paulsson (2008). "Effects of molecular memory and bursting on fluctuations in gene expression". Science. 319 (5861): 339–343. Bibcode:2008Sci...319..339P. doi:10.1126/science.1144331. PMID   18202292. S2CID   36135558.
  19. ↑ Hilfinger, A; J. Paulsson (2011). "Separating intrinsic from extrinsic fluctuations in dynamic biological systems". Proc. Natl. Acad. Sci. U.S.A. 108 (29): 12167–12172. Bibcode:2011PNAS..10812167H. doi: 10.1073/pnas.1018832108 . PMC   3141918 . PMID   21730172.
  20. ↑ Lestas, I; G. Vinnicombe; J. Paulsson (2010). "Fundamental limits on the suppression of molecular fluctuations". Nature. 467 (7312): 174–8. Bibcode:2010Natur.467..174L. doi:10.1038/nature09333. PMC   2996232 . PMID   20829788.
  21. ↑ A Synthetic Oscillatory Network of Transcriptional Regulators; Michael Elowitz and Stanislas Leibler; Nature. 2000 Jan 20;403(6767):335-8.
  22. ↑ Potvin-Trottier, L; Lord ND; Vinnicombe G.; Paulsson J. (2016). "Synchronous long-term oscillations in a synthetic gene circuit". Nature. 538 (7626): 514–517. Bibcode:2016Natur.538..514P. doi:10.1038/nature19841. PMC   5637407 . PMID   27732583.
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