User:Lance Martin
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Electronic memory & logic devices
Devices
- Transistors
- Logic gates
- Latches
- D-type flip-flops
- JK flip-flops
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
Architectures
- Cascade
- Asynchronous
- Synchronous
Summary presentation
References
Native biological memory & logic
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
- Recombination
- Nice overview
- Serine Recombinases
- Tyrosine Recombinases
- DNA methylation
- Error prone DNAp
- DSB & repair
- Timekeeping (James Ferrell)
- Feedback loops (James Ferrell)
Biological computation
- Arkin: computation in biochemical networks
- Chemical implementation of finite state machine
- Chemical implementation of Turing machine
Design of engineered biological systems
Basic construction / design principles
- Summary of reviews by
- Voight, Endy, Arkin
Computational modeling to aid design
- Review of
- Collins toggle switch
- Elowitz repressilator
Past engineered biological memory & logic devices/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
- Ham & Arkin inversion switch
- Harvard/BU 2004 iGem Int/Xis inversion switch & counter
- Their final presentation
- My notes on this work
- DNA methylation switch
My projects
Gemini
- Summary
- synBERC poster
- Current focus
- What is the unique application for compact (LacZa-GFP) dual reporter?
- What is the dynamic range (transfer function) for the LacZa-GFP fusion construct?
- Sequence: understand what we have.
- Determine method to modulate PoPS input (use the existing, different promoters or build with inducible promoter).
- Set up assays (plate reader for GFP and beta-gal)
- How does this compare to full length LacZ-GFP fusion, GFP, and LacZ?
- With information from the above in hand, determine additional work necessary to make genetically identical constructs (same promoter, RBS, reporters – from Meagan)
Modeling recombinase-driven genetic counters
- What are the key questions that we want a model to help us answer?
- 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
