The Sixth q-bio Summer School: Synthetic Biology

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In this theme, students will learn how to use computational modeling tools for design and evaluation of synthetic gene networks. We will review basic modeling approaches including Boolean networks, mass action kinetics, stochastic simulation algorithms and provide hands-on training sessions on using corresponding software tools. Then we will apply these tools to the design and analysis of basic elements of synthetic circuits such as positive and feedback loops, oscillators, toggle switches, logical gates, quorum-sensing circuits, enzymatic machinery. Issues of stochasticity, cell-to-cell variability, robustness and parameter sensitivity will be addressed in depth in regards to evaluation of synthetic circuit performance.

Contents

Lecturers

Project Mentors

  • Will Mather
  • Mike Ferry
  • Jangir Selimkhanov
  • Brooks Taylor
  • Phillip Samayoa

Topics

  • Biochemical Reaction Kinetics: Elementary Reactions, Law of Mass Action,

Generalized Mass Action, Chemical Equilibrium, Enzyme Kinetics, Stochastic Reaction Kinetics

  • Promoter Dynamics: Repressor-Operator Binding, Alternative Reaction Paths,

Cooperative Transcription Factor Binding, Synergism in RNA Polymerase Binding, DNA looping

  • Simple cis-regulatory Systems: Plac promoter, Gal1 promoter
  • Complex cis-regulatory Systems: Hierarchical Representations, cis-regulatory

Computational Logic

  • Positive and Negative Feedback
  • Bistable Switches: Lambda and the Engineered Toggle Switch
  • Logic gates and pulse generators
  • Genetic Oscillators: positive-negative feedback, time-delayed negative feedback,

segmentation clock

  • Signaling cascades and regulatory motifs
  • Sources of gene expression noise: translational bursting, transcriptional bursting,

transcription factor fluctuations

  • Noise in gene networks: feedback systems - reduction by negative feedback and

amplification by positive feedback

  • Noise-induced transitions and bistability

Suggested Reading

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