title: Synchronizing stochastic circadian oscillators in single cells of Neurospora crassa.
abstract: The synchronization of stochastic coupled oscillators is a central problem in physics and an emerging problem in biology, particularly in the context of circadian rhythms. Most measurements on the biological clock are made at the macroscopic level of millions of cells. Here measurements are made on the oscillators in single cells of the model fungal system, Neurospora crassa, with droplet microfluidics and the use of a fluorescent recorder hooked up to a promoter on a clock controlled gene-2 (ccg-2). The oscillators of individual cells are stochastic with a period near 21 hours (h), and using a stochastic clock network ensemble fitted by Markov Chain Monte Carlo implemented on general-purpose graphical processing units (or GPGPUs) we estimated that >94% of the variation in ccg-2 expression was stochastic (as opposed to experimental error). To overcome this stochasticity at the macroscopic level, cells must synchronize their oscillators. Using a classic measure of similarity in cell trajectories within droplets, the intraclass correlation (ICC), the synchronization surface ICC is measured on >25,000 cells as a function of the number of neighboring cells within a droplet and of time. The synchronization surface provides evidence that cells communicate, and synchronization varies with genotype.
authors: College of Engineering, University of Georgia, Athens, GA 30602, USA.
authors: Zhaojie
authors: Z
authors: Deng
authors: Department of Entomology, University of Georgia, Athens, GA 30602, USA.
authors: Sam
authors: S
authors: Arsenault
authors: Department of Statistics, University of Georgia, Athens, GA 30602, USA.
authors: Cristian
authors: C
authors: Caranica
authors: Genetics Department, University of Georgia, Athens, GA 30602, USA.|College of Agricultural and Environmental Sciences, University of Georgia, Athens, GA 30602, USA.
authors: James
authors: J
authors: Griffith
authors: College of Engineering, University of Georgia, Athens, GA 30602, USA.
authors: Taotao
authors: T
authors: Zhu
authors: Department of Biomedical Systems and Informatics Engineering, Yarmouk University, Irbid, 21163, Jordan.
authors: Ahmad
authors: A
authors: Al-Omari
authors: Department of Physics and Astronomy, University of Georgia, Athens, GA 30602, USA.
authors: Heinz-Bernd
authors: HB
authors: Schüttler
authors: Genetics Department, University of Georgia, Athens, GA 30602, USA.
authors: Jonathan
authors: J
authors: Arnold
authors: College of Engineering, University of Georgia, Athens, GA 30602, USA.
authors: Leidong
authors: L
authors: Mao
mesh_terms: D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004867:Equipment Design; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D056656:Lab-On-A-Chip Devices; D009492:Neurospora crassa / Q000166:cytology* / Q000502:physiology; D053038:Quorum Sensing; D059010:Single-Cell Analysis / Q000295:instrumentation / Q000379:methods*; D013269:Stochastic Processes