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Multicellular Computing Using Conjugation for Wiring

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Angel Goñi-Moreno,  Martyn Amos, Fernando de la Cruz

"Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing system under different conditions, and provide baseline information for future laboratory implementations."


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Genomic basis for the convergent evolution of electric organs

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Jason R. Gallant et al.

"Little is known about the genetic basis of convergent traits that originate repeatedly over broad taxonomic scales. The myogenic electric organ has evolved six times in fishes to produce electric fields used in communication, navigation, predation, or defense. We have examined the genomic basis of the convergent anatomical and physiological origins of these organs by assembling the genome of the electric eel (Electrophorus electricus) and sequencing electric organ and skeletal muscle transcriptomes from three lineages that have independently evolved electric organs. Our results indicate that, despite millions of years of evolution and large differences in the morphology of electric organ cells, independent lineages have leveraged similar transcription factors and developmental and cellular pathways in the evolution of electric organs."

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GENOME REVEALS HOW ELECTRIC FISH GOT ‘HIGH VOLTAGE’
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Gerd Moe-Behrens
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Synthetic therapeutic gene circuits in mammalian cells

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Florian Groher, Beatrix Suess

"Within the last decade, it has become obvious that RNA plays an important role in regulating gene expression. This has led to a plethora of approaches aiming at exploiting the outstanding chemical properties of RNA to develop artificial RNA regulators for conditional gene expression systems. Consequently, many different regulators have been developed to act on various stages of gene expression. They can be engineered to respond to almost any ligand of choice and are, therefore, of great interest for applications in synthetic biology. This review presents an overview of such engineered riboswitches, discusses their applicability and points out recent trends in their development. This article is part of a Special Issue entitled: Riboswitches."

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Mathematics with DNA, other way to do arithmetic operation using DNA
Numerical System is essential to write specific symbol as number and to create complex mathematical equations or formulas. In this article describes numerical system in base 4, which uses the nucleotides of DNA strand (A, G, ...
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Gerd Moe-Behrens
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Nano-Robots That Compute With DNA Installed Into Living Cockroach

http://bit.ly/1hhIBg6
 Gives a whole new meaning to the term "computer bug." 
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A Biological 2-Input Decoder Circuit in Human Cells

by
Guinn M, Bleris L.

"Decoders are combinational circuits that convert information from n-inputs to a maximum of 2n outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinatorial system can be valuable towards engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions."


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Engineers design 'living materials': Hybrid materials combine bacterial cells with nonliving elements that emit light http://bit.ly/1jDzhBI
Inspired by natural materials such as bone -- a matrix of minerals and other substances, including living cells -- engineers have coaxed bacterial cells to produce biofilms that can incorporate nonliving materials, such as gold nanoparticles and quantum dots. These "living materials" combine the advantages of live cells, which respond to their environment, produce complex biological molecules, and span multiple length scales, with the benefits of...
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Talk by Andrew Hessel: Programming Living Things - The Next Generation Of Computing http://bit.ly/1gud85F
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Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals

by
Evan J Olson,         Lucas A Hartsough,         Brian P Landry,         Raghav Shroff         & Jeffrey J Tabor

"Gene circuits are dynamical systems that regulate cellular behaviors, often using protein signals as inputs and outputs. Here we have developed an optogenetic 'function generator' method for programming tailor-made gene expression signals in live bacterial cells. We designed precomputed light sequences based on experimentally calibrated mathematical models of light-switchable two-component systems and used them to drive intracellular protein levels to match user-defined reference time courses. We used this approach to generate accelerated and linearized dynamics, sinusoidal oscillations with desired amplitudes and periods, and a complex waveform, all with unprecedented accuracy and precision. We also combined the function generator with a dual fluorescent protein reporter system, analogous to a dual-channel oscilloscope, to reveal that a synthetic repressible promoter linearly transforms repressor signals with an approximate 7-min delay. Our approach will enable a new generation of dynamical analyses of synthetic and natural gene circuits, providing an essential step toward the predictive design and rigorous understanding of biological systems."
http://bit.ly/OipvLb


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Rice synthetic biologists shine light on genetic circuit analysis

by
Jade Boyd

"Bioengineers invent ‘light tube array,’ ‘bioscilloscope’ to test, debug genetic circuits

In a significant advance for the growing field of synthetic biology, Rice University bioengineers have created a toolkit of genes and hardware that uses colored lights and engineered bacteria to bring both mathematical predictability and cut-and-paste simplicity to the world of genetic circuit design.
“Life is controlled by DNA-based circuits, and these are similar to the circuits found in electronic devices like smartphones and computers,” said Rice bioengineer Jeffrey Tabor, the lead researcher on the project. “A major difference is that electrical engineers measure the signals flowing into and out of electronic circuits as voltage, whereas bioengineers measure genetic circuit signals as genes turning on and off.”

In a new paper appearing online today in the journal Nature Methods, Tabor and colleagues, including graduate student and lead author Evan Olson, describe a new, ultra high-precision method for creating and measuring gene expression signals in bacteria by combining light-sensing proteins from photosynthetic algae with a simple array of red and green LED lights and standard fluorescent reporter genes. By varying the timing and intensity of the lights, the researchers were able to control exactly when and how much different genes were expressed.

“Light provides us a powerful new method for reliably measuring genetic circuit activity,” said Tabor, an assistant professor of bioengineering who also teaches in Rice’s Ph.D. program in systems, synthetic and physical biology. “Our work was inspired by the methods that are used to study electronic circuits. Electrical engineers have tools like oscilloscopes and function generators that allow them to measure how voltage signals flow through electrical circuits. Those measurements are essential for making multiple circuits work together properly, so that more complex devices can be built. We have used our light-based tools as a biological function generator and oscilloscope in order to similarly analyze genetic circuits.”
...."

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Gerd Moe-Behrens
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How to Make a Synthetic Multicellular Computer

by
Macia J, Sole R

"Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined."


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Gerd Moe-Behrens
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Modular Riboswitch Toolsets for Synthetic Genetic Control in Diverse Bacterial Species

by
Robinson CJ, Vincent HA, Wu MC, Lowe PT, Dunstan MS, Leys D, Micklefield J.

"Ligand-dependent control of gene expression is essential for gene functional analysis, target validation, protein production and metabolic engineering. However, the expression tools currently available are difficult to transfer between species and exhibit limited mechanistic diversity. Here we demonstrate how the modular architecture of purine riboswitches can be exploited to develop orthogonal and chimeric switches that are transferable across diverse bacterial species, modulating either transcription or translation, to provide tuneable activation or repression of target gene expres-sion, in response to synthetic non-natural effector molecules. Our novel riboswitch-ligand pairings are shown to regulate physiologically important genes required for bacterial motility in Escherichia coli and cell morphology in Bacillus subtilis. These findings are relevant for future gene function studies and antimicrobial target validation, whilst providing new modular and orthogonal regulatory components for deployment in synthetic biology regimes."

 http://bit.ly/1sXYZtg
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Sequence Elements Distal to the Ligand Binding Pocket Modulate the Efficiency of a Synthetic Riboswitch

by
Weigand JE, Gottstein-Schmidtke SR, Demolli S, Groher F, Duchardt-Ferner E, Wöhnert J, Suess B.

"Synthetic riboswitches can serve as sophisticated genetic control devices in synthetic biology, regulating gene expression through direct RNA-ligand interactions. We analyzed a synthetic neomycin riboswitch, which folds into a stem loop structure with an internal loop important for ligand binding and regulation. It is closed by a terminal hexaloop containing a U-turn and a looped-out adenine. We investigated the relationship between sequence, structure, and biological activity in the terminal loop by saturating mutagenesis, ITC, and NMR. Mutants corresponding to the canonical U-turn fold retained biological activity. An improvement of stacking interactions in the U-turn led to an RNA element with slightly enhanced regulatory activity. For the first position of the U-turn motif and the looped out base, sequence-activity relationships that could not initially be explained on the basis of the structure of the aptamer-ligand complex were observed. However, NMR studies of these mutants revealed subtle relationships between structure and dynamics of the aptamer in its free or bound state and biological activity."

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Sensors for Micro Bio Robots via Synthetic Biology

by
Edward B. Steager, Denise Wong, Deepak Mishra, Ron Weiss and Vijay Kumar

"Microscale robots offer an unprecedented oppor- tunity to perform tasks at resolutions approaching 1 μm, but the great majority of research to this point focuses on actuation and control. Potential applications for microrobots can be considerably expanded by integrating sensing, signal processing and feedback into the system. In this work, we demonstrate that technologies from the field of synthetic biology may be directly integrated into microrobotic systems to create cell- based programmable mobile sensors, with signal processors and memory units. Specifically, we integrate genetically engineered, ultraviolet light-sensing bacteria with magnetic microrobots, creating the first controllable biological microrobot that is capable of exploring, recording and reporting on the state of the microscale environment. We demonstrate two proof-of-concept prototypes: (a) an integrated microrobot platform that is able to sense biochemical signals, and (b) a microrobot platform that is able to deploy biosensor payloads to monitor biochemical signals, both in a biological environment. These results have important implications for integrated micro-bio-robotic systems for applications in biological engineering and research."

http://bit.ly/1vAxxzE
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A synthetic biology approach to bio-chem-ICT: first moves towards chemical communication between synthetic and natural cells

by
iordano Rampioni, Fabio Mavelli, Luisa Damiano, Francesca D’Angelo, Marco Messina, Livia Leoni, Pasquale Stano

"In this article we present novel aspects of the impact that synthetic biology (SB) can express in a field traditionally based on computer science: information and communication technologies (ICTs), an area that we will consider taking into account also possible implications for artificial intelligence (AI) research. In the first part of this article we will shortly introduce some recent theoretical and experimental issues related to our approach in SB, discussing their relevance and potentiality in the field. Next, we define an original SB research programme that aims at contributing to the development of bio-chem-ICTs and AI based on chemical communication between natural and synthetic cells. In particular we present (i) a mathematical model that allows us to simulate the main features of the system under construction; and (ii) preliminary wet-lab experiments showing the feasibility of our research programme. Based on the bottom-up construction of synthetic cells, the traits of this novel approach and their connections with recent conceptual and technological trends are finally discussed."


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Rapid and tunable post-translational coupling of genetic circuits

by
Arthur Prindle, Jangir Selimkhanov, Howard Li, Ivan Razinkov, Lev S. Tsimring & Jeff Hasty

"One promise of synthetic biology is the creation of genetic circuitry that enables the execution of logical programming in living cells. Such ‘wet programming’ is positioned to transform a wide and diverse swathe of biotechnology ranging from therapeutics and diagnostics to water treatment strategies. Although progress in the development of a library of genetic modules continues apace1, 2, 3, 4, a major challenge for their integration into larger circuits is the generation of sufficiently fast and precise communication between modules5, 6. An attractive approach is to integrate engineered circuits with host processes that facilitate robust cellular signalling7. In this context, recent studies have demonstrated that bacterial protein degradation can trigger a precise response to stress by overloading a limited supply of intracellular proteases8, 9, 10. Here we use protease competition to engineer rapid and tunable coupling of genetic circuits across multiple spatial and temporal scales. We characterize coupling delay times that are more than an order of magnitude faster than standard transcription-factor-based coupling methods (less than 1 min compared with ~20–40 min) and demonstrate tunability through manipulation of the linker between the protein and its degradation tag. We use this mechanism as a platform to couple genetic clocks at the intracellular and colony level, then synchronize the multi-colony dynamics to reduce variability in both clocks. We show how the coupled clock network can be used to encode independent environmental inputs into a single time series output, thus enabling frequency multiplexing (information transmitted on a common channel by distinct frequencies) in a genetic circuit context. Our results establish a general framework for the rapid and tunable coupling of genetic circuits through the use of native ‘queueing’ processes such as competitive protein degradation."

 http://bit.ly/1hGY7NV
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Slime mold microfluidic logical gates

by
Andrew Adamatzky, Theresa Schubert

"We demonstrate how logical operations can be implemented in ensembles of protoplasmic tubes of acellular slime mold Physarum polycephalum. The tactile response of the protoplasmic tubes is used to actuate analogs of two- and four-input logical gates and memory devices. The slime mold tube logical gates display results of logical operations by blocking flow in mechanically stimulated tube fragments and redirecting the flow to output tube fragments. We demonstrate how XOR and NOR gates are constructed. We also exemplify circuits of hybrid gates and a memory device. The slime mold based gates are non-electronic, simple and inexpensive, and several gates can be realized simultaneously at sites where protoplasmic tubes merge."


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"Programmable bacteria detect and record an environmental signal in the mammalian gut*

by
Jonathan W. Kotula, S. Jordan Kernsa, Lev A. Shaket, Layla Sirajb, James J. Collins, Jeffrey C. Way, and Pamela A. Silver

"Significance

The human microbiota represents the trillions of bacteria that live on the skin, in the oral, nasal, and aural cavities, and throughout the gastrointestinal tract. The species that live in the gastrointestinal tract, the gut microbiota, closely interact with host cells and have a profound impact on health. To develop tools to effectively monitor the gut microbiota and ultimately help in disease diagnosis, we have engineered Escherichia coli to sense and record environmental stimuli, and demonstrated that E. coli with such memory systems can survive and function in the mammalian gut. This work demonstrates that E. coli can be engineered into living diagnostics capable of nondestructively probing the mammalian gut.

Abstract
The mammalian gut is a dynamic community of symbiotic microbes that interact with the host to impact health, disease, and metabolism. We constructed engineered bacteria that survive in the mammalian gut and sense, remember, and report on their experiences. Based on previous genetic memory systems, we constructed a two-part system with a “trigger element” in which the lambda Cro gene is transcribed from a tetracycline-inducible promoter, and a “memory element” derived from the cI/Cro region of phage lambda. The memory element has an extremely stable cI state and a Cro state that is stable for many cell divisions. When Escherichia coli bearing the memory system are administered to mice treated with anhydrotetracycline, the recovered bacteria all have switched to the Cro state, whereas those administered to untreated mice remain in the cI state. The trigger and memory elements were transferred from E. coli K12 to a newly isolated murine E. coli strain; the stability and switching properties of the memory element were essentially identical in vitro and during passage through mice, but the engineered murine E. coli was more stably established in the mouse gut. This work lays a foundation for the use of synthetic genetic circuits as monitoring systems in complex, ill-defined environments, and may lead to the development of living diagnostics and therapeutics."


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I'm here with limited knowledge,  but unlimited interest and rudimentary questions:
Can the DNA mutate during a life span of a species? 
If yes how is biometric authentication possible?
If no how is genetic engineering possible?
I think it will take me hours to research this information on the internet, but hoping someone here can provide a paragraph answer with links that I can read in minutes. 
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I will  try a rough answer: Somatic mutations (often in single cells) are possible during your lifespan and can have serious consequences such as cancer. http://en.wikipedia.org/wiki/Somatic_mutation The DNA sample is most likely not taken from the cell with a mutation. There will be in any case enough unique information left to identify you.  http://en.wikipedia.org/wiki/DNA_profiling
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