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David karig thesis

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Therefore, while our system does not specifically address the issue of speed in molecular communication, it can be broadly applied to systems where issues of speed have been better resolved. Furthermore, our system does address the propagation distance aspect of molecular communication, doing so by harnessing noise in the system.

Our model assumes a forced flow through the channel and captures only one-way coupling between cell mimic wells in the array. However, one-way coupling is not a necessary condition for stochastic resonance. In general, backward propagating forces such as diffusion can hinder the performance of stochastic resonance; however, stochastic resonance can still be engineered [ 60 ].

In addition, the flow rate in these systems is generally controllable [ 41 ]. Inherent in the use of a Hill equation here is the assumption that these reactions are fast relative to other reactions in the system and that operator noise is insignificant [ 74 ].

As indicated by the scoring function results, our system preserves time varying signal information over long distances. However, the mean level of AHL can be high for distant array locations. It is likely that a wider exploration of parameter space would help to address this issue. Although Table 2 indicates that all parameters in the system can be physically tuned, we primarily focused on varying the flow rates c a and c m , the input amplitude k f , and the AHL decay rate d a.

Furthermore, a more complex genetic system would enable more precise tuning of the potential function of the switch to help alleviate the high mean signal concentrations at far distances. Finally, a non-uniform channel shape, i. Nonetheless, our results demonstrate that noise can be employed in a bio-inspired system to preserve information over long distances.

The precision and flexibility of the nanofabrication approach lend to scaling the system up to large numbers of compartments in a robust and repeatable fashion. One major challenge will involve loading the channels with the proper reagents and achieving a defined flow. Additionally, to scale up the system, the genetic network must be carefully tuned as discussed previously, and one area for future study is to extend and optimize the proposed genetic network to operate over even longer distances.

One immediate implication of this work is that the role of noise in nanoscale systems must be carefully characterized and considered in design. Moreover, our proposed system exemplifies one of many possible ways that noise can be gainfully harnessed. Our system shows that stochastic resonance can be implemented with genetic components in a nanocommunication system and thus illustrates the synergism between gene network design, fabrication approaches, and noise biology.

While the theory of stochastic resonance was originally derived to explain periodic climate changes of the earth, the phenomenon has been applied to a number of different fields [ 55 , 56 , 75 ]. An interesting question is whether natural biological systems use similar stochastic resonance mechanisms to harness noise for signal propagation. For example, it could theoretically be helpful in propagating signals through colonies of bacteria or for intracellular signaling in larger eukaryotic cells.

Stochastic resonance has already been implicated in circadian rhythms and in neural signaling [ 76 - 78 ]. Our proposed system offers a platform for investigating the fundamental aspects of these questions. The Las sender and receiver plasmids used in the Figure 1 experiments were constructed in Dr. Department of Energy. This work was performed at Oak Ridge National Laboratory. David K. He earned his B. Piro Siuti received his B.

Mitchel J. Roy D. Dar received his B. Michael Simpson is expected in Scott T. Scott received his B. Scott currently works on a variety of projects that connect state of the art nanofabrication and characterization techniques with fundamental biomedical research. He received his B. His research interests focus at the intersection of biological and nanoscale systems.

His laboratory is involved in the development of analytical technologies for post-genomics studies with specific emphases on molecular and cellular imaging techniques and the use of nanomaterials to study and mimic biological systems.

Michael L. He made key contributions to the introduction of custom integrated circuits to medium and high energy physics instrumentation before moving his research to the interfaces of engineering, physical sciences, and biology. In this arena Simpson made important contributions to the use of nanotechnology to enable the transfer of information across the biological-synthetic device boundary and the development of a fundamental understanding of Noise Biology.

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form.

Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. National Center for Biotechnology Information , U. Nano Commun Netw. Author manuscript; available in PMC Mar 1. Karig , a Piro Siuti , b, c Roy D.

Dar , a, d Scott. Retterer , a, b Mitchel J. Doktycz , a, b and Michael L. Author information Copyright and License information Disclaimer. Karig , ude. Siuti , vog. Dar , vog. Retterer , vog. Doktycz , vog. Copyright notice. See other articles in PMC that cite the published article. Abstract Cells offer natural examples of highly efficient networks of nanomachines. Keywords: stochastic resonance, synthetic biology, noise, quorum sensing, cell mimic.

Introduction Given the remarkable properties of the cell [ 1 , 2 ] coupled with its ability to communicate and interact with other cells, it is not surprising that the idea of harnessing biological function for engineering applications at the nano scale has drawn much attention [ 3 - 6 ].

Background and Related Work Over the past decade, components of Gram negative bacterial quorum sensing systems have been employed in synthetic biology efforts to forward engineering cooperative behavior in living cells. Open in a separate window.

Materials and Methods 4. Model For our modeling study, we assume that we have a channel consisting of an array of adjacent cell mimic wells. Results To quantify the fidelity of signal propagation at the n th array well, we calculate a performance measure B F based on a previously defined metric for resonant systems [ 60 ].

Discussion Our proposed system for exploring the use of noise to aid propagation of a time-varying AHL signal exemplifies the importance of interdisciplinary research in nanocommunication. Acknowledgements The Las sender and receiver plasmids used in the Figure 1 experiments were constructed in Dr.

Brief Biography David K. Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. Nano-enabled synthetic biology. Mol Syst Biol. Engineering in the biological substrate: information processing in genetic circuits.

Proceedings of the IEEE. Biological excitable media based on non-excitable cells and calcium signaling. Nano Communication Networks. Molecular communication: Harnessing biochemical materials to engineer biomimetic communication systems. Engineered biological nanofactories trigger quorum sensing response in targeted bacteria. Nat Nano. Nanonetworks: A new communication paradigm. Computer Networks. Mechanisms and function of intercellular calcium signaling. Molecular and Cellular Endocrinology.

Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Feedback control of morphogenesis in fungi by aromatic alcohols. Genes Dev. Annual Review of Cell and Developmental Biology. J Bacteriol. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide.

Mol Microbiol. DNA Computing. Engineered communications for microbial robotics; pp. Genetic circuit building blocks for cellular computation, communications, and signal processing. Natural Computing. Engineering signal processing in cells: Towards molecular concentration band detection. Spatiotemporal control of gene expression with pulse-generating networks.

A synthetic multicellular system for programmed pattern formation. Synchronizing genetic relaxation oscillators by intercell signaling. A synchronized quorum of genetic clocks. Promoter specificity elements in Pseudomonas aeruginosa quorum-sensing-controlled genes. Signal-amplifying genetic circuit enables in vivo observation of weak promoter activation in the Rhl quorum sensing system.

Biotechnol Bioeng. Interchangeability and specificity of components from the quorum-sensing regulatory systems of Vibrio fischeri and Pseudomonas aeruginosa. Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium. A synthetic Escherichia coli predator-prey ecosystem. Annual Review of Physical Chemistry. Self-Assembled Nanoreactors.

Chemical Reviews. Enzymes inside lipid vesicles: preparation, reactivity and applications. Biomolecular Engineering. A Communication interface using vesicles embedded with channel forming proteins in molecular communication; Bio-Inspired Models of Network, Information and Computing Systems; ; Bionetics Liposomes: technologies and analytical applications.

Journal of Membrane Biology. The minimal size of liposome-based model cells brings about a remarkably enhanced entrapment and protein synthesis. Synthesis of functional protein in liposome. J Biosci Bioeng. Gene expression within cell-sized lipid vesicles. Expression of a cascading genetic network within liposomes. FEBS Lett. Toward an artificial cell based on gene expression in vesicles. Phys Biol. Nano Letters. Cell mimics created from the controlled synthesis and directed assembly of carbon nanofibers; Bio Micro and Nanosystems Conference, Development and fabrication of nanoporous silicon-based bioreactors within a microfluidic chip.

Lab on a Chip. BSEC Noise in biological circuits. Wiley Interdiscip Rev Nanomed Nanobiotechnol. Complex mathematical models of biology at the nanoscale. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. Frequency domain analysis of noise in autoregulated gene circuits. Engineering stability in gene networks by autoregulation. Gene network shaping of inherent noise spectra.

Phenotypic consequences of promoter-mediated transcriptional noise. Mol Cell. Transient-mediated fate determination in a transcriptional circuit of HIV. Nat Genet. Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Internal noise stochastic resonance of synthetic gene network. Chemical Physics Letters. Physical Review Letters. Engineered internal noise stochastic resonator in gene network: A model study.

Biophysical Chemistry. What is stochastic resonance? Definitions, misconceptions, debates, and its relevance to biology. PLoS Comput Biol. The mechanism of stochastic resonance. Journal of Physics A: Mathematical and General. Princeton University; Engineering multi-signal synthetic biological systems. Efficient cell-free expression with the endogenous E.

Coli RNA polymerase and sigma factor Journal of Biological Engineering. Signal transmission in one-way coupled bistable systems: Noise effect. Physical Review E. The chemical Langevin equation. The Journal of Chemical Physics. Regulation of noise in the expression of a single gene. Nature, nurture, or chance: stochastic gene expression and its consequences.

Tuning and controlling gene expression noise in synthetic gene networks. Nucleic Acids Res. Distribution and regulation of stochasticity and plasticity in Saccharomyces cerevisiae. Stability and Noise in Biochemical Switches. Advances in Neural Information Processing. MIT Press; Cambridge: Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol. Cell-free synthetic biology: a bottom-up approach to discovery by design. A universal RNAi-based logic evaluator that operates in mammalian cells.

Nat Biotech. Construction of an in vitro bistable circuit from synthetic transcriptional switches. Tying new knots in synthetic biology. HFSP J. Frequency domain chemical Langevin analysis of stochasticity in gene transcriptional regulation. Journal of Theoretical Biology. Stochastic resonance and sensory information processing: a tutorial and review of application.

Clin Neurophysiol. Internal noise stochastic resonance in a circadian clock system. Stochastic resonance in biology. How noise can enhance detection of weak signals and help improve biological information processing. Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase.

Study of messenger RNA inactivation and protein degradation in an Escherichia coli cell-free expression system. J Biol Eng. J Biol Chem. Support Center Support Center. External link. Enabling bacteria to talk to one another is useful for dividing complex tasks among multiple populations of bacteria.

These extracts contain the components that are essential for making new proteins. This allows us to do synthetic biology in vitro. One advantage is safety. Whereas there may be concerns with using engineered microbes in the environment for remediation or sensing, cell free systems cannot self-replicate. There are a number of advantages in terms of the flexibility of cell-free systems as well. Besides cell-free systems, I have also been working on microbiome research, in particular the human skin microbiome.

We are taking an interdisciplinary approach to understanding why individuals have very different microbiomes, how microbial communities vary spatially across the body, and the relationship between skin properties and skin microbes. Overall, this research has relevance not only to issues such as skin diseases and wound infections, but also to vector-borne diseases. For instance, certain bacteria on the skin produce volatile compounds that either attract or repel disease carrying arthropods such as mosquitoes.

What was the transition from electrical engineering to a biology-intensive research direction like? Moving from purely computational work to incorporating a large amount of experimental biology was a major lifestyle change. It often felt like bacteria controlled my life by deciding when to grow and how to behave. However, once I adapted, it became thrilling to see how living things work. I ended up really enjoying making new DNA constructs and also found microscopy particularly fun.

However, a lot of research is ultimately about learning what you need on the fly. I was eventually able to realize the benefit of interdisciplinary work — the ability to come from a different perspective and see things in a different light. Tell us more about yourself Outside of research, I love the outdoors and music and, when I can find the time, I enjoy art and painting. My wife, Sharon Bewick, is an assistant professor in biology at Clemson. Clemson Bioengineering.

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