Endy:Notebook/Genetic Memory

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Team Members

 * Ton
 * Lu
 * Jerome
 * Drew
 * Carolina
 * Isis
 * Cesar

To Do

 * 1) Expand and refine applications list
 * 2) Brainstorm spinoff applications of component technologies (i.e., identify and define immediate payoffs)
 * 3) Design short and medium term experiments and goals
 * 4) Identify and prioritize grand challenges'
 * 5) Outline ideal writing plan

Executive Summary
Modest amounts of genetically encoded memory would be incredibly useful. For example, the equivalent of an 8-bit counter (allowing counting up to 256) would revolutionize the study of aging and cancer. As exciting, solving the practical challenges associated with implementing genetically-encoded memory requires considering and answering incredibly interesting puzzles associated with variation and reliability in the behavior of cellular and molecular systems.

Applications

 * Aging
 * For example, replace "counting of bud scars" (not the bud scars themselves) in yeast, with engineered yeast that remember and report their own age (e.g., via fluorescent reporters). See PMID 18616424. Might need a 5- or 6-bit counter to really impact yeast research.  Could collect enough cells to support many experiments, and new (for aging) kinds of experiments (e.g., RNA arrays, etc.).
 * See PMID 17875664 for an early example.
 * Could apply same counter to drive transducer / controller that was maintaining "young" gene expression levels
 * Development
 * Automatically record lineages as opposed to manual measurement (e.g., PMID 838129)
 * Cancer
 * Directed Evolution

(note, split applications into (a) consumer and (b) derivative)

Basic requirements

 * 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 ...

Tasty Organisms

 * Yeast (5- or 6-bit counters)
 * Worm (4- or 5-bit counters for development? Need to double check depth of worm's developmental lineage)
 * Mice?
 * Human (4- or 5-bit counters for development? Again, need to check depth of lineage; also, may need more for "cancer" related questions)
 * Note that should add bacteria and plants to this list, but haven't spec'd out applications yet (moss?)

Early Questions

 * What are the available / best physical mechanisms to store state?
 * How is state written?
 * How is state read?
 * How long do the read and write steps take?
 * How much energy is used to change or maintain state?
 * What determines spontaneous switching rates?
 * What device or system architecture(s) enable memory?
 * How are physical mechanics linked to architecture (e.g., do all mechanisms work for all architectures)
 * Can the mechanics of writing, storing, and reading be translated across species and kingdoms, w/o need to organism specific factors?

Biological Technologies

 * Writing Mechanisms
 * Storage Mechanisms
 * Epigenetic, DNA
 * Epigenetic, extra-DNA, molecular levels (e.g., Gardner et al. latch)
 * Location (e.g., cytoplasm vs. nuclear)
 * Noncovalent (e.g., protein-protein interactions)
 * Covalent (e.g., post-translational modification)
 * Reading Mechanisms

Natural Systems

 * Recombination
 * Recombinase notebook
 * DNA Methylation and Demethylation
 * Notebook
 * Error prone DNAp
 * Targeted gene evolution
 * DSB & repair
 * Zinc finger gene targeting
 * Zinc finger human gene correction
 * Timekeeping (James Ferrell)
 * Toggle switch at heart of circadian timekeeping
 * Cell cycle and its switches
 * Feedback loops (James Ferrell)
 * Interlinked positive and negative feedback loops
 * Systems level dissection of the cell cycle

Engineering Foundations

 * Past Examples
 * Electrical (Lu)
 * (starting reference on computer data storage, URL)
 * Mechanical (DE)
 * URL #1
 * URL #2
 * Fluidic (Ton)
 * (starting reference on fluidic logic, URL)
 * Biological (Jerome)
 * Natural biological memory systems
 * Engineered memory systems


 * Performance Characteristics
 * Spontaneous Switching Rate
 * Device Architecture
 * (note challenge -- are all device architectures the same, independent of substrate, or not?)

Meeting notes
Infinite monkey group meeting 31 Oct 2008

Related Notebooks

 * Ton's memory banks


 * Jerome's notebook


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