The pedestrian watchmaker: Genetic clocks from engineered oscillators

The crucial role of time‐keeping has required organisms to develop sophisticated regulatory networks to ensure the reliable propagation of periodic behavior. These biological clocks have long been a focus of research; however, a clear understanding of how they maintain oscillations in the face of unpredictable environments and the inherent noise of biological systems remains elusive. Here, we review the current understanding of circadian oscillations using Drosophila melanogaster as a typical example and discuss the utility of an alternative synthetic biology approach to studying these highly intricate systems.

[1]  Jeff Hasty,et al.  Monitoring dynamics of single-cell gene expression over multiple cell cycles , 2005, 2006 Bio Micro and Nanosystems Conference.

[2]  M. Elowitz,et al.  Reconstruction of genetic circuits , 2005, Nature.

[3]  Sangeeta N. Bhatia,et al.  Intracellular Delivery of Quantum Dots for Live Cell Labeling and Organelle Tracking , 2004 .

[4]  Ertugrul M. Ozbudak,et al.  Regulation of noise in the expression of a single gene , 2002, Nature Genetics.

[5]  J. F. Feldman,et al.  Isolation of circadian clock mutants of Neurospora crassa. , 1973, Genetics.

[6]  T. Baker,et al.  A specificity-enhancing factor for the ClpXP degradation machine. , 2000, Science.

[7]  A. Grossman Genetic networks controlling the initiation of sporulation and the development of genetic competence in Bacillus subtilis. , 1995, Annual review of genetics.

[8]  D. Sidote,et al.  Circadian Regulation of a Drosophila Homolog of the Mammalian Clock Gene: PER and TIM Function as Positive Regulators , 1998, Molecular and Cellular Biology.

[9]  Alex Groisman,et al.  A microfluidic chemostat for experiments with bacterial and yeast cells , 2005, Nature Methods.

[10]  J. Hasty,et al.  Synthetic gene network for entraining and amplifying cellular oscillations. , 2002, Physical review letters.

[11]  M. Rosbash,et al.  Two Novel doubletime Mutants Alter Circadian Properties and Eliminate the Delay between RNA and Protein inDrosophila , 2000, The Journal of Neuroscience.

[12]  S. Kay,et al.  Time zones: a comparative genetics of circadian clocks , 2001, Nature Reviews Genetics.

[13]  Ron Weiss,et al.  Engineered Communications for Microbial Robotics , 2000, DNA Computing.

[14]  C. Walker,et al.  CIRCADIAN RHYTHMS IN MICROORGANISMS : New Complexities , 2006 .

[15]  John J. Tyson,et al.  The Dynamics of Feedback Control Circuits in Biochemical Pathways , 1978 .

[16]  Jeff Hasty,et al.  Designer gene networks: Towards fundamental cellular control. , 2001, Chaos.

[17]  P. Hardin,et al.  Circadian oscillators of Drosophila and mammals , 2006, Journal of Cell Science.

[18]  James J. Collins,et al.  A Tunable Genetic Switch Based on RNAi and Repressor Proteins for Regulating Gene Expression in Mammalian Cells , 2007, Cell.

[19]  A. Levine,et al.  Surfing the p53 network , 2000, Nature.

[20]  L. Glass,et al.  Oscillation and chaos in physiological control systems. , 1977, Science.

[21]  M. W. Young,et al.  Changes in abundance or structure of the per gene product can alter periodicity of the Drosophila clock , 1987, Nature.

[22]  H. Bujard,et al.  Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements. , 1997, Nucleic acids research.

[23]  J. Sturm,et al.  Micro- and nanofluidics for DNA analysis , 2004, Analytical and bioanalytical chemistry.

[24]  J. Stelling,et al.  A tunable synthetic mammalian oscillator , 2009, Nature.

[25]  I. Edery,et al.  Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime , 2002, Nature.

[26]  Jeff Hasty,et al.  Engineered gene circuits , 2002, Nature.

[27]  S. Quake,et al.  Long-Term Monitoring of Bacteria Undergoing Programmed Population Control in a Microchemostat , 2005, Science.

[28]  S. Leibler,et al.  Biological rhythms: Circadian clocks limited by noise , 2000, Nature.

[29]  L. Serrano,et al.  Engineering stability in gene networks by autoregulation , 2000, Nature.

[30]  S. Golden,et al.  Circadian clock mutants of cyanobacteria. , 1994, Science.

[31]  A. Hoffmann,et al.  Transcriptional regulation via the NF-κB signaling module , 2006, Oncogene.

[32]  M. L. Simpson,et al.  Frequency domain analysis of noise in autoregulated gene circuits , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Hasty,et al.  Dynamics of single-cell gene expression , 2006, Molecular systems biology.

[34]  M. Bennett,et al.  A fast, robust, and tunable synthetic gene oscillator , 2008, Nature.

[35]  Jeff Hasty,et al.  Delay-induced degrade-and-fire oscillations in small genetic circuits. , 2009, Physical review letters.

[36]  R. Allada Circadian Clocks A Tale of Two Feedback Loops , 2003, Cell.

[37]  R. Sauer,et al.  The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. , 1998, Genes & development.

[38]  M. Chalfie GREEN FLUORESCENT PROTEIN , 1995, Photochemistry and photobiology.

[39]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[40]  S. Basu,et al.  A synthetic multicellular system for programmed pattern formation , 2005, Nature.

[41]  A. Ninfa,et al.  Development of Genetic Circuitry Exhibiting Toggle Switch or Oscillatory Behavior in Escherichia coli , 2003, Cell.

[42]  Jeff Hasty,et al.  A synthetic gene network for tuning protein degradation in Saccharomyces cerevisiae , 2007, Molecular systems biology.

[43]  M. Elowitz,et al.  A synthetic oscillatory network of transcriptional regulators , 2000, Nature.

[44]  J. Hasty,et al.  Synchronizing genetic relaxation oscillators by intercell signaling , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[45]  O. Pourquié The Segmentation Clock: Converting Embryonic Time into Spatial Pattern , 2003, Science.

[46]  J. Dunlap Molecular Bases for Circadian Clocks , 1999, Cell.

[47]  J. Levine,et al.  Surfing the p53 network , 2000, Nature.

[48]  M. Savageau Comparison of classical and autogenous systems of regulation in inducible operons , 1974, Nature.

[49]  D. Endy Foundations for engineering biology , 2005, Nature.

[50]  A. Sehgal,et al.  Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. , 1994, Science.

[51]  Satchidananda Panda,et al.  Circadian rhythms from flies to human , 2002, Nature.

[52]  William Paley Natural theology : or, evidences of the existence and attributes of the Deity : collected from the appearances of nature , 2018 .

[53]  Thomas K. Darlington,et al.  Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. , 1998, Science.

[54]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[55]  M. W. Young,et al.  double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation , 1998, Cell.

[56]  François Rouyer,et al.  The F-box protein Slimb controls the levels of clock proteins Period and Timeless , 2002, Nature.

[57]  Clive Richards,et al.  The Blind Watchmaker , 1987, Bristol Medico-Chirurgical Journal.

[58]  P. Hardin,et al.  Interlocked feedback loops within the Drosophila circadian oscillator. , 1999, Science.

[59]  P. Hardin,et al.  The Circadian Timekeeping System of Drosophila , 2005, Current Biology.

[60]  R J Konopka,et al.  Clock mutants of Drosophila melanogaster. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[61]  M. W. Young,et al.  A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock , 2001, Cell.

[62]  Oliver T. Fackler,et al.  The Nef Protein of Human Immunodeficiency Virus Establishes Superinfection Immunity by a Dual Strategy to Downregulate Cell-Surface CCR5 and CD4 , 2005, Current Biology.

[63]  Jie Chen,et al.  A Complex Oscillating Network of Signaling Genes Underlies the Mouse Segmentation Clock , 2006, Science.

[64]  Noo Li Jeon,et al.  Patterned cell culture inside microfluidic devices. , 2005, Lab on a chip.