Showing papers by "John Bechhoefer published in 2015"

Replication timing is regulated by the number of MCMs loaded at origins

Abstract: Replication timing is a crucial aspect of genome regulation that is strongly correlated with chromatin structure, gene expression, DNA repair, and genome evolution. Replication timing is determined by the timing of replication origin firing, which involves activation of MCM helicase complexes loaded at replication origins. Nonetheless, how the timing of such origin firing is regulated remains mysterious. Here, we show that the number of MCMs loaded at origins regulates replication timing. We show for the first time in vivo that multiple MCMs are loaded at origins. Because early origins have more MCMs loaded, they are, on average, more likely to fire early in S phase. Our results provide a mechanistic explanation for the observed heterogeneity in origin firing and help to explain how defined replication timing profiles emerge from stochastic origin firing. These results establish a framework in which further mechanistic studies on replication timing, such as the strong effect of heterochromatin, can be pursued.

High-Precision Test of Landauer's Principle in a Feedback Trap

Abstract: We confirm Landauer's 1961 hypothesis that reducing the number of possible macroscopic states in a system by a factor of 2 requires work of at least kTln2. Our experiment uses a colloidal particle in a time-dependent, virtual potential created by a feedback trap to implement Landauer's erasure operation. In a control experiment, similar manipulations that do not reduce the number of system states can be done reversibly. Erasing information thus requires work. In individual cycles, the work to erase can be below the Landauer limit, consistent with the Jarzynski equality.

Hidden Markov models for stochastic thermodynamics

Abstract: The formalism of state estimation and hidden Markov models can simplify and clarify the discussion of stochastic thermodynamics in the presence of feedback and measurement errors. After reviewing the basic formalism, we use it to shed light on a recent discussion of phase transitions in the optimized response of an information engine, for which measurement noise serves as a control parameter. The HMM formalism also shows that the value of additional information displays a maximum at intermediate signal-to-noise ratios. Finally, we discuss how systems open to information flow can apparently violate causality; the HMM formalism can quantify the performance gains due to such violations.

What is superresolution microscopy

Abstract: In this paper, we discuss what is, what is not, and what is only sort of superresolution microscopy. We begin by considering optical resolution, first in terms of diffraction theory, then in terms of linear-systems theory, and finally in terms of techniques that use prior information, nonlinearity, and other tricks to improve resolution. This discussion reveals two classes of superresolution microscopy, “pseudo” and “true.” The former improves images up to the diffraction limit, whereas the latter allows for substantial improvements beyond the diffraction limit. The two classes are distinguished by their scaling of resolution with photon counts. Understanding the limits to imaging resolution involves concepts that pertain to almost any measurement problem, implying a framework with applications beyond optics.

Hidden Markov models for stochastic thermodynamics

Abstract: The formalism of state estimation and hidden Markov models (HMMs) can simplify and clarify the discussion of stochastic thermodynamics in the presence of feedback and measurement errors. After reviewing the basic formalism, we use it to shed light on a recent discussion of phase transitions in the optimized response of an information engine, for which measurement noise serves as a control parameter. The HMM formalism also shows that the value of additional information shows a maximum at intermediate signal-to-noise ratios. Finally, we discuss how systems open to information flow can apparently violate causality; the HMM formalism can quantify the performance gains due to such violations.

Feedback trap with scattering-based illumination

Abstract: Feedback traps can explore particle dynamics in virtual potentials. They periodically measure particle position and, after each measurement, apply a force imposed by the potential. Here, a scattering-based illumination improves particle position measurements and bandwidth.

When Wall-hindered Diffusion Dynamics Becomes Non-Gaussian

Abstract: We design and implement a feedback tracking system to study the correlated diffusive properties of a Brownian colloidal sphere near a flat wall. A feedback-controlled piezo vertical stage tracks the sphere’s position.