User:Lance Martin: Difference between revisions

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===Modeling recombinase-driven genetic counters===
===Modeling recombinase-driven genetic counters===


*What are the key questions that we want a model to help us answer?
[http://openwetware.org/wiki/Endy:Notebook/Computational_modeling#Steps_in_flipee_mechanism_for_modeling Notebook]
**What is counter's dynamic behavior across a range of parameter settings within both asynchronous and synchronous system architectures?
**Which architecture is more reliable (exhibits "robust" counting) across the range of parameters?
 
*What do we need to know in order to build a model that answers our questions?
**Desired dynamic behavior of our system (e.g. counting within cell division timescale, etc)
**How much do we need to know about flipee performance (e.g latency, transfer function, etc)?
**Defined state variables (e.g. recombinase mRNA/protein, excisionase mRNA/protein, the bits, etc)
**Defined parameters that describe dynamic behavior of the state variable
**(e.g. gene expression rate, recombinase-DNA association and dissociation rates, etc)
 
*Lay out model architecture and build it
**parameters from mathematical model for recombinase kinetics provide foundation
**iGem 2004 model serves as an example and provides additional foundation

Revision as of 15:13, 29 March 2009

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Electronic memory & logic devices

Abstraction hierarchy

Devices

Summary presentation

Media: Electronic_Memory_&_Logic_Devices.ppt

References

Horowitz & Hill Electronics tree Very strong overview of circuits: DC, AC, Semi-conductors, Digital

Electronic counters & system architecture

Decision tree

Architectures

  • Cascade
  • Asynchronous
  • Synchronous

Summary presentation

Media:Electronic_Counters.ppt

References

Synchronous counters

Native biological memory & logic

A biological bit

Basic requirements for memory & logic

  • Big picture
    • Reliably holds state
    • Controllable state change
  • Then, degenerates into many application-specific requirements
    • What are the applications for memory and logic in biological systems?
    • How do naturally evolved mechanisms break down between combinatorial and sequential logic?
    • Need a chart listing all mechanisms with associated cellular applications, requirements, timescale ...

Native systems

Biological computation

Design of engineered biological systems

Design process

Basic construction / design principles

  • Summary of reviews by
    • Voight, Endy, Arkin

Media: Principles.ppt

Computational modeling to aid design

  • Review of
    • Collins toggle switch
    • Elowitz repressilator

Media:Modeling.ppt

Past engineered biological memory & logic devices/systems

Some engineered biological memory & logic systems

Rationale

Scaling to larger applications with more states and deeper sequential logics is a future need. Systems whose output depends on input history are necessary for sophisticated computation and information storage. Memory is common in systems that control functions such as development. Memory may confer fitness advantage for synthetic systems that exist and compete in the living world. (reference: Arkin, Ham 2008)

Challenges

  • No spatial addressing of signals in biological systems
  • Many heterogeneous parts implemented, resulting in:
    • Heterogeneity of device physics across circuits
    • Complex properties, making design and modeling hard
    • Large outlays of DNA real-estate may be necessary
    • Large energetic loads on host state

Of particular interest to us

My projects

LacZ alpha-GFP fusion

Gemini

Modeling recombinase-driven genetic counters

Notebook