Kinetic Intersections as a Source of Information on Rate Coefficients

C

Robot control with biological cells

At present there exists a large gap in size, performance, adaptability and robustness between natural and artificial information processors for performing coherent perception-action tasks under real-time constraints. Even the simplest organisms have an enviable capability of coping with an unknown dynamic environment. Robots, in contrast, are still clumsy if confronted with such complexity. This paper presents a bio-hybrid architecture developed for exploring an alternate approach to the control of autonomous robots. Circuits prepared from amoeboid plasmodia of the slime mold Physarum polycephalum are interfaced with an omnidirectional hexapod robot. Sensory signals from the macro-physical environment of the robot are transduced to cellular scale and processed using the unique micro-physical features of intracellular information processing. Conversely, the response form the cellular computation is amplified to yield a macroscopic output action in the environment mediated through the robot’s actuators

Relating topology and dynamics in cell signaling networks

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 153-163).Cells are constantly bombarded with stimuli that they must sense, process, and interpret to make decisions. This capability is provided by interconnected signaling pathways. Many of the components and interactions within pathways have been identified, and it is becoming clear that the precise dynamics they generate are necessary for proper system function. However, our understanding of how pathways are interconnected to drive decisions is limited. We must overcoming this limitation to develop interventions that can fine tune a cell decision by modulating specific features of its constituent pathway's dynamics. How can we quantatively map a whole cell decision process? Answering this question requires addressing challenges at three scales: the detailed biochemistry of protein-protein interactions, the complex, interlocked feedback loops of transcriptionally regulated signaling pathways, and the multiple mechanisms of connection that link distinct pathways together into a full cell decision process. In this thesis, we address challenges at each level. We develop new computational approaches for identifying the interactions driving dynamics in protein-protein networks. Applied to the cyanobacterial clock, these approaches identify two coupled motifs that together provide independent control over oscillation phase and period. Using the p53 pathway as a model transcriptional network, we experimentally isolate and characterize dynamics from a core feedback loop in individual cells. A quantitative model of this signaling network predicts and rationalizes the distinct effects on dynamics of additional feedback loops and small molecule inhibitors. Finally, we demonstrated the feasibility of combining individual pathway models to map a whole cell decision: cell cycle arrest elicited by the mammalian DNA damage response. By coupling modeling and experiments, we used this combined perspective to uncover some new biology. We found that multiple arrest mechanisms must work together in a proper cell cycle arrest, and identified a new role for p21 in preventing G2 arrest, paradoxically through its action on G1 cyclins. This thesis demonstrates that we can quantitatively map the logic of cellular decisions, affording new insight and revealing points of control.by Jared E. Toettcher.Ph.D

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 197, September 1979

This bibliography lists 193 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1979

Does the Potential for Chaos Constrain the Embryonic Cell-Cycle Oscillator?

Although many of the core components of the embryonic cell-cycle network have been elucidated, the question of how embryos achieve robust, synchronous cellular divisions post-fertilization remains unexplored. What are the different schemes that could be implemented by the embryo to achieve synchronization? By extending a cell-cycle model previously developed for embryos of the frog Xenopus laevis to include the spatial dimensions of the embryo, we establish a novel role for the rapid, fertilization-initiated calcium wave that triggers cell-cycle oscillations. Specifically, in our simulations a fast calcium wave results in synchronized cell cycles, while a slow wave results in full-blown spatio-temporal chaos. We show that such chaos would ultimately lead to an unpredictable patchwork of cell divisions across the embryo. Given this potential for chaos, our results indicate a novel design principle whereby the fast calcium-wave trigger following embryo fertilization synchronizes cell divisions

Graph Theory and Networks in Biology

In this paper, we present a survey of the use of graph theoretical techniques in Biology. In particular, we discuss recent work on identifying and modelling the structure of bio-molecular networks, as well as the application of centrality measures to interaction networks and research on the hierarchical structure of such networks and network motifs. Work on the link between structural network properties and dynamics is also described, with emphasis on synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape

Cellular Gate Technology

We propose a biochemically plausible mechanism for constructing digital logic signals and gates of significant complexity within living cells. These mechanisms rely largely on co-opting existing biochemical machinery and binding proteins found naturally within the cell, replacing difficult protein engineering problems with more straightforward engineering of novel combinations of gene control sequences and gene coding regions. The resulting logic technology, although slow, allows us to engineer the chemical behavior of cells for use as sensors and effectors. One promising use of such technology is the control of fabrication processes at the molecular scale.DARPA/ONR Ultrascale Computing Program under contract N00014-96-1-1228 and by the DARPA Embedded Computing Program under contract DABT63-95-C130

Circadian Clock Proteins in Prokaryotes: Hidden Rhythms?

Circadian clock genes are vital features of eukaryotes that have evolved such that organisms can adapt to our planet's rotation in order to anticipate the coming day or night as well as unfavorable seasons. This circadian clock uses oscillation as a timekeeping element. However, circadian clock mechanisms exist also in prokaryotes. The circadian clock of Cyanobacteria is well studied. It is regulated by a cluster of three genes: kaiA, kaiB, and kaiC. In this review, we will discuss the circadian system in cyanobacteria, and provide an overview and updated phylogenetic analysis of prokaryotic organisms that contain the main circadian genes. It is evident that the evolution of the kai genes has been influenced by lateral transfers but further and deeper studies are needed to get an in depth understanding of the exact evolutionary history of these genes. Interestingly, Legionella pneumophila an environmental bacterium and opportunistic human pathogen that parasitizes protozoa in fresh water environments also contains kaiB and kaiC, but their functions are not known. All of the residues described for the biochemical functions of the main pacemaker KaiC in Synechococcus elongatus are also conserved in the L. pneumophila KaiC protein