Design of translationally controlled artificial gene regulation (and more!)

Stefan Hammer, Sven Findeiß, Christoph Flamm, Ivo Hofacker

Doubice 2016

Is designing RNA easy?

Actually... yes!

A C G G U A C U G G A A C U C G

Packages to solve the problem:

  • RNAblueprint
  • PyDesign (might be renamed)
  • ViennaRNA Package
  • NUPACK Package

RNAblueprint

A library for smart sequence sampling
https://github.com/ribonets

  • Get RNA sequences...
    • compatible to all structural constraints
    • and to sequence constraints
    • fairly drawn from whole solution space
    • with various sampling move steps
    • Hammer S, B Tschiatschek, C Flamm, IL Hofacker, S Findeiß. 2016. RNAblueprint: Flexible and universal multiple target nucleic acid sequence design. Bioinformtics, submitted

PyDesign

A python module for effortless designing RNA molecules
https://github.com/ribonets

  • Helps you to...
    • define your molecule states
    • call various package functions (ViennaRNA, NUPACK)
    • use precoded optimization methods
    • compose your objectives and optimization goals

Translationally controlled artificial gene regulation

sRNA mediated translational OFF switch:

What is needed?

  • Structural constraints
  • Sequence constraints (RBS, start-codon)
  • Sequence context (reporter gene sequence)
  • Optimization method and sampling move step
  • Objective function

Objective Function

Temperature sensitive RNA molecule

RNA molecule folding into three different states at certain temperatures:

(((((((((((((....)))))))))))))  5°C
(((((.....)))))(((((.....))))) 10°C
(((((.....)))))............... 37°C
5°C
10°C
37°C

What is needed?

  • Structural constraints
  • Optimization method and sampling move step
  • Objective function:

    Flamm C et al. 2001. “Design of Multistable RNA Molecules.” RNA 7 (2): 254–65.

Can I also do that?

Acknowledgements

  • Sven Findeiß
  • Peter Kerpedjiev
  • Birgit Tschiatschek
  • Christoph Flamm
  • Ivo Hofacker