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| ==Electronic memory & logic devices==
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| [[Image:Electronic Devices.jpg|thumb|right|Abstraction hierarchy]]
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| ===Devices===
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| *Transistors
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| **[[Media: Transistor Detail.ppt]]
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| *Logic gates
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| *Latches
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| *D-type flip-flops
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| *JK flip-flops
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| ===Summary presentation===
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| [[Media: Electronic_Memory_&_Logic_Devices.ppt]]
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| ===References===
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| [http://books.google.com/books?id=bkOMDgwFA28C&dq=horowitz+and+hill+the+art+of+electronics&printsec=frontcover&source=bn&hl=en&ei=zDfISdS4NoG0sAOax5V2&sa=X&oi=book_result&resnum=7&ct=result Horowitz & Hill]
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| [http://hyperphysics.phy-astr.gsu.edu/Hbase/Electronic/etroncon.html#c1 Electronics tree]
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| [http://www.allaboutcircuits.com/vol_4/chpt_3/5.html Very strong overview of circuits: DC, AC, Semi-conductors, Digital]
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| ==Electronic counters & system architecture== | | ==Projects== |
| [[Image:Counter Architecture.jpg|thumb|right|Decision tree]]
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| ===Architectures=== | | ===Electronic counter review=== |
| *Cascade
| | [http://openwetware.org/wiki/Endy:Notebook/Electronic_counters Electronic counter notebook] |
| *Asynchronous
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| *Synchronous
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| ===Summary presentation=== | | ===Gemini=== |
| [[Media:Electronic_Counters.ppt]] | | [http://openwetware.org/wiki/Endy:Notebook/Gemini Gemini notebook] |
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| | ===Simulation=== |
| | [http://openwetware.org/wiki/Endy:Notebook/Computational_modeling#Steps_in_flipee_mechanism_for_modeling Computational modeling notebook] |
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| | ===Genetic switches: methylation & feedback regulation=== |
| | [http://openwetware.org/wiki/Endy:Notebook/Genetic_switches:_feedback%2C_methylation%2C_%26_more Genetic switches notebook] |
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| ===References=== | | ===Recombination switches=== |
| [http://www.allaboutcircuits.com/vol_4/chpt_11/3.html Synchronous counters] | | [http://openwetware.org/wiki/Endy:Notebook/Review_of_recombinases Review of recombinases] |
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| ==Native biological memory & logic== | | ==Assorted items of interest== |
| [[Image:Inversion.jpg|thumb|right|A biological bit]] | | [[Image:Inversion.jpg|thumb|right|A biological bit]] |
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| ===Basic requirements for memory & logic=== | | ===James Ferrell=== |
| *Big picture
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| **Reliably holds state
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| **Controllable state change
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| *Then, degenerates into many application-specific requirements
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| **What are the applications for memory and logic in biological systems?
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| **How do naturally evolved mechanisms break down between combinatorial and sequential logic?
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| **Need a chart listing all mechanisms with associated cellular applications, requirements, timescale ...
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| ===Native systems===
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| *Recombination
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| **[http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.73.011303.073908 Nice overview]
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| **Serine Recombinases
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| *** [http://www3.interscience.wiley.com/journal/118923247/abstract?CRETRY=1&SRETRY=0 Diversity in Ser recombinases]
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| *** [http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0040186&ct=1 BxB1 directionality]
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| *** [[Media:Recombinases.ppt]]
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| **Tyrosine Recombinases
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| *** [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WK7-45S48WH-F&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=db485e9dbaa8d2b7c4b57104b4de03bb Kinetic analysis of Flp and Cre]
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| *** [[Media:Mechanism.ppt]]
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| *DNA methylation
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| **[http://en.wikipedia.org/wiki/Epigenetics Epigenetics]
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| **[http://en.wikipedia.org/wiki/DNA_methylation DNA methylation]
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| **[http://en.wikipedia.org/wiki/Genomic_imprinting#Imprinting_mechanisms Genomic imprinting]
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| *Error prone DNAp
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| **[http://www.pnas.org/content/100/17/9727.abstract Targeted gene evolution]
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| *DSB & repair
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| **[http://www.nature.com/nbt/journal/v23/n8/abs/nbt1125.html Zinc finger gene targeting]
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| **[http://www.nature.com/nature/journal/v435/n7042/abs/nature03556.html Zinc finger human gene correction]
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| *Timekeeping (James Ferrell) | | *Timekeeping (James Ferrell) |
| **[http://www.sciencemag.org/cgi/content/summary/318/5851/757?ck=nck Toggle switch at heart of circadian timekeeping] | | **[http://www.sciencemag.org/cgi/content/summary/318/5851/757?ck=nck Toggle switch at heart of circadian timekeeping] |
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| *[http://www.pnas.org/content/88/24/10983.abstract Chemical implementation of Turing machine] | | *[http://www.pnas.org/content/88/24/10983.abstract Chemical implementation of Turing machine] |
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| ==Design of engineered biological systems==
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| [[Image:Process.jpg|thumb|right|Design process]] | | [[Image:Process.jpg|thumb|right|Design process]] |
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| [[Media:Modeling.ppt]] | | [[Media:Modeling.ppt]] |
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| ==Past engineered biological memory & logic devices/systems==
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| [[Image:PriorWork.jpg|thumb|right|Some engineered biological memory & logic systems]] | | [[Image:PriorWork.jpg|thumb|right|Some engineered biological memory & logic systems]] |
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| ===Rationale=== | | ===Prior work: implementing recombinase switches=== |
| 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)
| | *Ham & Arkin inversion switch |
| | **[[Media:Ham&Arkin.ppt]] |
| | *Harvard/BU 2004 iGem Int/Xis inversion switch & counter |
| | **Their final presentation |
| | ***[[Media:iGem.ppt]] |
| | **Notes on this work |
| | ***[[Media:iGemLance.ppt]] |
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| ===Challenges=== | | ===Challenges=== |
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| **Large outlays of DNA real-estate may be necessary | | **Large outlays of DNA real-estate may be necessary |
| **Large energetic loads on host state | | **Large energetic loads on host state |
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| ===Of particular interest to us===
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| *Ham & Arkin inversion switch
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| **[[Media:Ham&Arkin.ppt]]
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| *Harvard/BU 2004 iGem Int/Xis inversion switch & counter
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| **Their final presentation
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| ***[[Media:iGem.ppt]]
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| **My notes on this work
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| ***[[Media:iGemLance.ppt]]
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| *DNA methylation switch
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| **[http://www.ncbi.nlm.nih.gov/pubmed/14992728 Switch]
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| **[http://www.cell.com/molecular-cell/abstract/S1097-2765(04)00064-4 Switch, again]
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| **[http://www.ncbi.nlm.nih.gov/pubmed/17262027 Switch gives bi-stable gene expression]
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| ==My projects==
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| [[Image:Gemini.jpg|thumb|right|LacZ alpha-GFP fusion]]
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| ===Gemini===
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| *Summary
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| **[[Media:Gemini.ppt]]
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| *synBERC poster
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| **[[Media:GeminiPoster.pdf]]
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| *Notebook
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| **[Endy:Notebook/Gemini]
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| ===Modeling recombinase-driven genetic counters===
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| *What are the key questions that we want a model to help us answer?
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| **What is counter's dynamic behavior across a range of parameter settings within both asynchronous and synchronous system architectures?
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| **Which architecture is more reliable (exhibits "robust" counting) across the range of parameters?
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| *What do we need to know in order to build a model that answers our questions?
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| **Desired dynamic behavior of our system (e.g. counting within cell division timescale, etc)
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| **How much do we need to know about flipee performance (e.g latency, transfer function, etc)?
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| **Defined state variables (e.g. recombinase mRNA/protein, excisionase mRNA/protein, the bits, etc)
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| **Defined parameters that describe dynamic behavior of the state variable
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| **(e.g. gene expression rate, recombinase-DNA association and dissociation rates, etc)
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| *Lay out model architecture and build it
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| **parameters from mathematical model for recombinase kinetics provide foundation
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| **iGem 2004 model serves as an example and provides additional foundation
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