Julius B. Lucks/Bibliography/Simpson-TrendsBiotechnol-19-2001

= Notes on Simpson-TrendsBiotechnol-19-2001 =


 * complex tasks performed by cells: sensing, navigation, communication, cooperation, nano-fabrication
 * review on mimicing man-made information processing inside cells
 * to accomplish tasks, need memory, sensing, feedback, communication
 * E. coli - 2 micrometer^2 cross section - 4.6 x 10^6 bp chromosome - equiv 9.2 megabit memory
 * how arrive at this number?
 * 4300 diff polypeptides produced from several hundred diff promoters
 * compare to semiconductors International Technology Roadmap for Semiconductors
 * by 2014, memory density 24.5 Gbits/cm^2 and logic transistor density 664 M/cm^2
 * assuming 4 transistors per logic function (how get this?), 2 micrometer^2 Si could contain 490-bit memory with 3 simple logic gates
 * bacterial cells, viewed as 'devices' - tolerate a wide array of conditions
 * can integrate them in 3D structures
 * biofilm formation an alternative to lithography and other manufacturing techniques neccesary for Si integrated circuits
 * BBIC - bioluminescent bioreporter integrated circuit (4-8)
 * present 3 examples of sensing/information processing/actuation that occurs in natural cells
 * directed motility (chemotaxis, phototaxis, magnetotaxis (12-14))
 * symbiotic collonization as a communications system, esp. to initially establish the relationship
 * Hawaiian squid Euprymna scolopes with lumincescent Vibrio fisheri (24)
 * Upon colonization V. fischeri looses flagella, reduces cell size, decreases growth rate, enhances luminescence (25,26)
 * group formation (biofilms) - members have some protection from phage, biocides, antibiotics
 * 'silicon mimetic' approach to engineering cell information processing
 * engineered genetic regulatory functions emulate the functionality of silicon semiconductor devices
 * silicon paradigm - three terminal device in which transport between 2 of the terminals controlled by a signal at the third (FET)
 * biochemical analogy - substrate-enzyme-product controlled by some effector acting on the enzyme (bipolar junction transistor) (32,33)
 * hardware interconnects not needed
 * Fig 2 shows the lux system in V. fischerei used in the BBIC that implements this design - control of light production by O2 and FMNH2 modulation of luciferase activity
 * realizing logic gates with genetic machinery
 * the key to logic gates is interconnectivity
 * constructing gene transcription modules for biochemical devices that are logic circuits (Knight's group - 9,10)
 * this group working on AND, OR and XOR
 * implementing OR
 * use 2 promoters that behave same as transcription factors, but are affected by 2 diff effectors
 * use 1 promoter that respots same way to 2 diff inhibitors - tod-lux fusion in P. putida TVA8 (induced by trichloroethylene and toluene)
 * combinations of AND, OR and XOR can implement any combinatorial logic function - but CANNOT be used for sequential circuits that require memory of past logic states and clock signal synchronization
 * Gardner, Cantor, Collins - one-bit memory using double repressor toggle switch (uses lamba cI and part of Lac operon - ('Construction of a Genetic toggle switch in E. coli' 35) (see also Kobayashi-PNAS-101-2004 )
 * 'challenge - develop genetic circuit that makes more eff use of cells DNA memory capacity'''
 * Elowitz and Liebler repressilator can be used as clock (36) (why not also cell cycle?)
 * interconnecting
 * needed for even moderate complexity
 * suggest using cell-to-cell signals to connect - isolating single gate inside a cell
 * quorum sensing via N-acyl-homoseine lactones (AHLs) - diffusable cell-to-cell signals present in many Gram-negative bacteria (37)
 * V. fischeri - luxI encodes AHL synthetase, luxR encodes AHL-dependant transcriptional activator
 * primary consideration is number of molecules in circuits and the amoun of cross-talk
 * (39) - P. aeruginosa and V. fischerei AHL systems don't interact
 * Input/Output
 * review on EMF and electric current pulses in living cells (43) - little data on how effects gene expression - need to know this for hybrid systems - Fig 6 describes their experiment towars this investigation
 * noise
 * finite period of time necc for an effector to reach operational concentration, certain time needed for it to decay below operational concentration as well
 * outcomes of genetic networks not deterministic (44,45)
 * problem for non-linear circuits with bifurcations since can cause non-boolean, probabilistic responses
 * simulating such circuits - Gillespi algorithm - see Adam's paper on Bio-SPICE (48)

= References =


 * 1) Julius B. Lucks/Bibliography