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Systems and Synthetic Biology: How the Cell Solves Problems, Fall 2010

Systems and Synthetic Biology:  How the Cell Solves Problems, Fall 2010 | SynBioFromLeukipposInstitute | Scoop.it

MIT OpenCourseWare

MIT OpenCourseWare (OCW) is a web-based publication of virtually all MIT course content. OCW is open and available to the world and is a permanent MIT activity.
"A millennial challenge in biology is to decipher how vast arrays of molecular interactions inside the cell work in concert to produce a cellular function. Systems biology, a new interdisciplinary field of science, brings together biologists and physicists to tackle this grand challenge through quantitative experiments and models. In this course, we will discuss the unifying principles that all organisms use to perform cellular functions. We will also discuss key challenges faced by a cell in both single and multi-cellular organisms. Finally, we will discuss how researchers in the field of synthetic biology are using the new knowledge gained from studying naturally-occurring biological systems to create artificial gene networks capable of performing new functions."
http://bit.ly/mJWClZ

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All in a day’s work: Design and print your own robot - MIT News Office

All in a day’s work: Design and print your own robot - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it

MIT project, funded with $10 million NSF grant, could transform robotic design and production...

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PLoS ONE: Comprehensive Analysis of Gene-Environmental Interactions with Temporal Gene Expression Profiles in Pseudomonas aeruginosa

PLoS ONE: Comprehensive Analysis of Gene-Environmental Interactions with Temporal Gene Expression Profiles in Pseudomonas aeruginosa | SynBioFromLeukipposInstitute | Scoop.it

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Kangmin Duan, William M. McCullough, Michael G. Surette, Tony Ware, Jiuzhou Song
"To explore gene-environment interactions, based on temporal gene expression information, we analyzed gene and treatment information intensively and inferred interaction networks accordingly. The main idea is that gene expression reflects the response of genes to environmental factors, assuming that variations of gene expression occur under different conditions. Then we classified experimental conditions into several subgroups based on the similarity of temporal gene expression profiles. This procedure is useful because it allows us to combine diverse gene expression data as they become available, and, especially, allowing us to lay the regulatory relationships on a concrete biological basis. By estimating the activation points, we can visualize the gene behavior, and obtain a consensus gene activation order, and hence describe conditional regulatory relationships. The estimation of activation points and building of synthetic genetic networks may result in important new insights in the ongoing endeavor to understand the complex network of gene regulation."
http://bit.ly/IULQr1

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Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice

Remotely controlled gene expression

 

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Sarah A. Stanley, Jennifer E. Gagner, Shadi Damanpour, Mitsukuni Yoshida, Jonathan S. Dordick, Jeffrey M. Friedman

"Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca2+-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells."
http://bit.ly/L8uyJS

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A Startup Uses the Cloud to Unravel DNA - Technology Review

A Startup Uses the Cloud to Unravel DNA - Technology Review | SynBioFromLeukipposInstitute | Scoop.it

DNAnexus thinks cloud computing can help analyze sequenced DNA and push personalized medicine forward.

 
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Jay Keasling to deliver final Heuermann lecture

Jay Keasling to deliver final Heuermann lecture | SynBioFromLeukipposInstitute | Scoop.it
Jay Keasling talk "The Bold Future of Alternative Energy"

"Nebraska native and synthetic biology pioneer Jay Keasling will deliver "The Bold Future of Alternative Energy" as the final Heuermann Lecture series Tuesday.
Keasling, CEO of the Joint BioEnergy Institute in Emeryville, Calif., will speak at 2:30 p.m. in the Hardin Hall Auditorium on the University of Nebraska-Lincoln East Campus. A 2 p.m. reception precedes the lecture.
Keasling and colleagues have engineered a strain of E. coli bacteria to produce biodiesel fuel from biomass such as switchgrass without the need of enzyme additives. Now they are seeking ways to make their discovery economically competitive.
Keasling is the 2010 recipient of the Presidential Green Chemistry Challenge Award from the U.S. Environmental Protection Agency and numerous other awards.
Heuermann lectures focus on providing and sustaining food, natural resources and renewable energy and securing the sustainability of rural communities. For more information, visit http://heuermannlectures.unl.edu."
http://bit.ly/J0Wc8p

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From Soil Microbe to Super-Efficient Biofuel Factory? « Berkeley Lab News Center

From Soil Microbe to Super-Efficient Biofuel Factory? « Berkeley Lab News Center | SynBioFromLeukipposInstitute | Scoop.it

"Is there a new path to biofuels hiding in a handful of dirt? Lawrence Berkeley National Laboratory (Berkeley Lab) biologist Steve Singer leads a group that wants to find out. They’re exploring whether a common soil bacterium can be engineered to produce liquid transportation fuels much more efficiently than the ways in which advanced biofuels are made today.

The scientists are working with a bacterium called Ralstonia eutropha. It naturally uses hydrogen as an energy source to convert CO2 into various organic compounds.

The group hopes to capitalize on the bacteria’s capabilities and tweak it to produce advanced biofuels that are drop-in replacements for diesel and jet fuel. The process would be powered only by hydrogen and electricity from renewable sources such as solar or wind.

The goal is a biofuel—or electrofuel, as this new approach is called—that doesn’t require photosynthesis...."

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Artemisia annua: A Vital Partner in the Global Fight against Malaria | Bio 2.0 | Learn Science at Scitable

Artemisia annua: A Vital Partner in the Global Fight against Malaria | Bio 2.0 | Learn Science at Scitable | SynBioFromLeukipposInstitute | Scoop.it

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Eric Sawyer
"A number of months ago I wrote a brief post on artemisinin, often touted as the synthetic biology success story. Here is a much more thoroughly researched take on the topic, including recent news that this "miracle" drug is becoming susceptible to malaria parasite resistance.
Artemisia annua, known commonly as sweet wormwood, sweet Annie, and qinghao, is a shrub native to China long used both ornamentally and for medicinal purposes. A. annua is now cultivated globally as the only source of a potent anti-malarial drug, artemisinin. The drug is part of a cocktail of phytochemicals stored in glands on the leaves epidermis ("glandular trichomes,") which are used to deter browsers. Artemisinin has proved effective in the onslaught against the highly adaptable malaria parasite, which has already become resistant to many other drugs....."

http://bit.ly/IYi56T

 
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MIT and Harvard announce edX - MIT News Office

MIT and Harvard announce edX - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it
Joint partnership builds on MITx and Harvard distance learning; aims to benefit campus-based education and beyond.
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Synthetic biology could become the defining technology of the 21st century -Thinking Big: Synthetic Biology - Fidelity Investments

Synthetic biology could become the defining technology of the 21st century

Thinking Big: Synthetic Biology - Fidelity Investments
Video
"Goats are making silk stronger than steel, and we see opportunity. In this video from http://go.fidelity.com/ThinkBig about synthetic biology, Fidelity analyst Robert Chan explains why.

So what is synthetic biology? It's an approach to creating new organisms that fulfill specific functions, using nature as a manufacturing platform and DNA as the raw material. To date, scientists have created goats making spider silk in their milk (it's five times stronger than steel), salmon that grow twice as fast as normal, and bacteria that produce anti-malarial drugs and biodiesel. Each invention could radically increase the supply of these vital products.

As the science evolves -- it is still in a very early, experimental phase -- synthetic biology could become the defining technology of the 21st century, bringing with it new thinking, new questions, and new opportunities.

At Fidelity, we dig deeper into the big issues and hidden trends, using our global reach and expertise to give you smart investing ideas. Put the power of our insights to work for you at http://go.fidelity.com/ThinkBig.

Fidelity Brokerage Services LLC, Member NYSE, SIPC, 900 Salem Street, Smithfield, RI 02917 609830.4.0"http://bit.ly/IuqrX1

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Soapbox Science: Tool Tales: Leukippos – Synthetic Biology Lab in the Cloud : Soapbox Science

Soapbox Science: Tool Tales: Leukippos – Synthetic Biology Lab in the Cloud : Soapbox Science | SynBioFromLeukipposInstitute | Scoop.it
Science Online New York (SoNYC) encourages audience participation in the discussion of how science is carried out and communicated online.
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Playing with genes | COSMOS magazine

Playing with genes | COSMOS magazine | SynBioFromLeukipposInstitute | Scoop.it

by David Smith

"I KNOW IT’S BAD coffee-shop etiquette, but I keep peaking at the laptop computer screen of the young woman beside me. I see long stretches of A’s, T’s, G’s and C’s and a large colorful map of chromosomes. She’s definitely a geneticist.

“Sorry to disturb you,” I say, tilting my own laptop screen towards her, revealing a genome diagram, “but it looks like we’re both working on similar things.” Soon I’m telling her about my postdoctoral research on jellyfish genomes and she’s describing to me her work on salmon genetics. I ask her if she’s a PhD student. She laughs and says, “I’m actually interning as an investment analyst.”

She then explains how a few years ago a friend taught her some basic bioinformatics skills and how to download DNA sequences from the Internet. “Ever since, I’ve been assembling and analyzing genomes in my spare time. I have no formal training in biology, but I’ve learned the basics through a few introductory textbooks that I ordered online. It’s a weird hobby, but a great way to unwind from work and learn about evolution.”..."

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Synthetic Biology's Hunt for the Genetic Transistor - IEEE Spectrum

Synthetic Biology's Hunt for the Genetic Transistor - IEEE Spectrum | SynBioFromLeukipposInstitute | Scoop.it

By JULIUS B. LUCKS, ADAM P. ARKIN

"In 1977, a small group of researchers in California changed the world when they wrangled a common gut bacterium into producing a human protein. Using every technique in the book—and inventing some of their own—they scavenged, snipped, and glued together genetic components to synthesize a tiny filament of DNA. They then inserted the new segment into some Escherichia coli cells, tricking them into making the human hormone somatostatin.
A year later, these scientists had an E. coli strain that produced insulin, an invaluable drug in the treatment of diabetes. With that, the era of biotechnology was born. A plethora of novel—or at least cheaper—drugs seemed to loom on the horizon.
Thirty-odd years on, molecular biologists have delivered on many parts of that early promise, engineering microbes to produce a wide range of pharmaceuticals, including experimental antimalarial medicines and antibiotics. A quick glance in the pantry or storage closet is likely to reveal other products of genetic engineering, too, including foods, food additives and colorings, and even laundry detergent. The list goes on and on.
The economic impact of all this has been enormous. Genetic engineering and other forms of biotechnology account for some 40 percent of the recent growth in the U.S. gross domestic product, for example. The biotech sectors in other countries have also made sizable contributions to their economies. And you can expect that trend to continue as genetically engineered organisms tackle even more diverse challenges, such as producing renewable fuels and cleaning up toxic waste.
Genetic engineers have indeed accomplished a great deal....."
http://bit.ly/IiBksg

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Biochemist creates CO2-eating light that runs on algae | Geek.com

Biochemist creates CO2-eating light that runs on algae | Geek.com | SynBioFromLeukipposInstitute | Scoop.it

Video

"Our atmosphere is filling up with CO2 and we seem to be the major cause of that. The generally accepted solution seems to be cutting back on emissions as quickly as possible, but implementing such cuts is problematic because everyone has to agree to do more, which essentially ends up costing a lot of time and money.

There is an alternative to such measures, though. Instead of relying entirely on cutting emissions, why don’t we start taking CO2 out of the atmosphere? That’s exactly what biochemist Pierre Calleja is trying to do, and his solution almost sounds too good to be true.

Calleja has developed a lighting system that requires no electricity for power. Instead it draws CO2 from the atmosphere and uses it to produce light as well as oxygen as a byproduct. The key ingredient to this eco-friendly light? Algae."

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Automated Design of Genetic Toggle Switches With Predetermined Bistability

by

Shuobing Chen, Haoqian Zhang, Handuo Shi, Weiyue Ji, Jingchen Feng, Yan Gong, Zhenglin Yang, Qi Ouyang
Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijng, 100871, China

"Synthetic biology aims to rationally construct biological devices with required functionalities. Methods that automate the design of genetic devices without post-hoc adjustment, therefore, are highly desired. Here we provide a method to predictably design genetic toggle switches with predetermined bistability. To accomplish this task, a biophysical model that links Ribosome Binding Site (RBS) DNA sequence to toggle switch bistability was first developed by integrating a stochastic model with RBS design method. Then, to parameterize the model, a library of genetic toggle switch mutants was experimentally built, followed by establishing the equivalence between RBS DNA sequences and switch bistability. To test this equivalence, RBS nucleotide sequences for different specified bistability were in silico designed and experimentally verified. Results show that the deciphered equivalence is highly predictive for the toggle switch design with predetermined bistability. This method can be generalized to quantitative design of other probabilistic genetic devices in synthetic biology."

http://bit.ly/ItPEhH

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Revolution in Art & Design using 3D Printing | Objet for Neri Oxman

As seen on the Objet blog: http://blog.objet.com/

In this insightful interview, Neri Oxman,architect, designer and professor of Media Arts and Sciences and Director of the Mediated Matter group at the MIT Media Lab, explains the differences between 'additive' and 'subtractive' manufacturing. Inspired by things that 'grow' in nature, Oxman uses the world's most advanced 3D printing technology - the Objet Connex500 multi-material 3D printer to produce some incredible models which will be on display at the Pompidou Center until August 6th 2012 at the 'Multiversites Creatives' exhibit. Neri also explains 3D printing within the wider paradigm shift in technology and manufacturing - comparing it to the Gutenberg 2D print revolution of the 1440's.

For more information about Objet: http://www.objet.com/

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Search for Pore-fection

GENOME SEQUENCING
by

Elizabeth Pennisi
"Oxford Nanopore Technologies is set to achieve the first commercialization of a long-awaited and oft-doubted technology called nanopore sequencing. The technology, based on protein pores so tiny that 25,000 of them can fit on the cross section of a human hair, could be the next big thing in genome sequencing and analysis. Although they've gotten much cheaper and smaller in recent years, machines that read DNA and RNA still usually cost hundreds of thousands of dollars, take up entire lab benches, and require much upfront and postsequencing processing to generate a genome. Nanopore sequencing could change all that. But some scientists say many technical hurdles remain to be overcome before nanopore devices produce actual sequence data."

http://bit.ly/IPqcl6

 
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Robust Signal Processing in Living Cells

Robust Signal Processing in Living Cells | SynBioFromLeukipposInstitute | Scoop.it

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Ralf Steuer, Steffen Waldherr, Victor Sourjik, and Markus Kollmann

"Cellular signaling networks have evolved an astonishing ability to function reliably and with high fidelity in uncertain environments. A crucial prerequisite for the high precision exhibited by many signaling circuits is their ability to keep the concentrations of active signaling compounds within tightly defined bounds, despite strong stochastic fluctuations in copy numbers and other detrimental influences. Based on a simple mathematical formalism, we identify topological organizing principles that facilitate such robust control of intracellular concentrations in the face of multifarious perturbations. Our framework allows us to judge whether a multiple-input-multiple-output reaction network is robust against large perturbations of network parameters and enables the predictive design of perfectly robust synthetic network architectures. Utilizing the Escherichia coli chemotaxis pathway as a hallmark example, we provide experimental evidence that our framework indeed allows us to unravel the topological organization of robust signaling. We demonstrate that the specific organization of the pathway allows the system to maintain global concentration robustness of the diffusible response regulator CheY with respect to several dominant perturbations. Our framework provides a counterpoint to the hypothesis that cellular function relies on an extensive machinery to fine-tune or control intracellular parameters. Rather, we suggest that for a large class of perturbations, there exists an appropriate topology that renders the network output invariant to the respective perturbations."
http://1.usa.gov/ILkLXN

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Bristol University | News from the University | Clive Bowsher

Bristol University | News from the University | Clive Bowsher | SynBioFromLeukipposInstitute | Scoop.it

"A mathematician from the University of Bristol has teamed up with a biologist from the University of Edinburgh to address a major problem in molecular biology.

Dr Clive Bowsher, Lecturer at the School of Mathematics, and Professor Peter Swain at Synthetic and Systems Biology Edinburgh co-authored a paper in the Proceedings of the National Academy of Sciences showing how to separate ‘signal’ from ‘noise’ when studying the mechanisms of living cells.
Cells make decisions in fluctuating environments using inherently noisy biochemical mechanisms. Such effects create considerable, unpredictable variation – known as ‘stochasticity’– both over time and between genetically identical cells. To understand how cells exploit and control these biochemical fluctuations, scientists must identify the sources of stochasticity, quantify their effects, and distinguish variation that carries information about the biological environment from confounding noise...."
http://bit.ly/J6yV6I

refers to:

Identifying sources of variation and the flow of information in biochemical networks
by
Clive G. Bowshera, and Peter S. Swain
"To understand how cells control and exploit biochemical fluctuations, we must identify the sources of stochasticity, quantify their effects, and distinguish informative variation from confounding “noise.” We present an analysis that allows fluctuations of biochemical networks to be decomposed into multiple components, gives conditions for the design of experimental reporters to measure all components, and provides a technique to predict the magnitude of these components from models. Further, we identify a particular component of variation that can be used to quantify the efficacy of information flow through a biochemical network. By applying our approach to osmosensing in yeast, we can predict the probability of the different osmotic conditions experienced by wild-type yeast and show that the majority of variation can be informational if we include variation generated in response to the cellular environment. Our results are fundamental to quantifying sources of variation and thus are a means to understand biological “design.”..."
http://bit.ly/Kv4TpB

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MIT and Harvard launch a ‘revolution in education’ - MIT News Office

MIT and Harvard launch a ‘revolution in education’ - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it

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David L. Chandler, MIT News Office

"MIT President Susan Hockfield and Harvard University President Drew Faust, accompanied by top officials from both institutions, announced on Wednesday a new collaboration that will unite the Cambridge-based universities in an ambitious new partnership to deliver online education to learners anywhere in the world.

The new venture, called edX, will provide interactive classes from both Harvard and MIT — for free — to anyone in the world with an Internet connection. But a key goal of the project, Faust said, is “to enhance the educational experience of students who study in our classrooms and laboratories.”..."

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Publishing risky research : Nature : Nature Publishing Group

NATURE | EDITORIAL

"This week sees the online publication of the paper 'Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets' by the Japanese–US team headed by Yoshihiro Kawaoka at the University of Wisconsin-Madison (M. Imai et al. Nature 10.1038/nature10831 (2012). See also pages 7 and 13, and H.-L. Yen and J. S. M. Peiris Nature http://dx.doi.org/10.1038/nature11192; 2012). Kawaoka's paper was one of two submitted last August, reporting mammalian transmissibility of avian flu as a result of artificial genetic manipulation, the principal scientific interest of which arises from the small number of mutations found to be necessary. The other paper, by a team headed by Ron Fouchier at the Erasmus Medical Centre in Rotterdam, the Netherlands, is expected to appear soon in Science....."
http://bit.ly/IHaBdE

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A synthetic post-transcriptional controller to explore the modular design of gene circuits - ACS Synthetic Biology (ACS Publications)

A synthetic post-transcriptional controller to explore the modular design of gene circuits - ACS Synthetic Biology (ACS Publications) | SynBioFromLeukipposInstitute | Scoop.it

by
Francesca Ceroni, Simone Furini, Alessandra Stefan, Alejandro Hochkoeppler, and Emanuele Giordano
"The assembly from modular parts is an efficient approach for creating new devices in Synthetic Biology. In the Bottom-up designing strategy, modular parts are characterized in advance, and then mathematical modelling is used to predict the outcome of the final device. A prerequisite for Bottom-up design is that the biological parts behave in modular way when assembled together. We designed a new synthetic device for post-transcriptional regulation of gene expression, and tested if the outcome of the device can be described from the features of its components. Modular parts showed unpredictable behaviour when assembled in different complex circuits. This prevented a modular description of the device that was possible only under specific conditions. Our findings shed doubts into the feasibility of a pure Bottom-up approach in Synthetic Biology, highlighting the urgency for new strategies for the rational design of synthetic devices."

http://bit.ly/IEFUWE

 
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Refining Regulatory Net... [IEEE/ACM Trans Comput Biol Bioinform. 2012] - PubMed - NCBI

by
Zhang X, Moret BM.
"The experimental determination of transcriptional regulatory networks in the laboratory remains difficult and time-consuming, while computational methods to infer these networks provide only modest accuracy. The latter can be attributed partly to the limitations of a single-organism approach. Computational biology has long used comparative and evolutionary approaches to extend the reach and accuracy of its analyses. In this paper, we describe ProPhyC, a probabilistic phylogenetic model and associated inference algorithms, designed to improve the inference of regulatory networks for a family of organisms by using known evolutionary relationships among these organisms. ProPhyC can be used with various network evolutionary models and any existing inference method. Extensive experimental results on both biological and synthetic data confirm that our model (through its associated refinement algorithms) yields substantial improvement in the quality of inferred networks over all current methods. We also compare ProPhyC with a transfer learning approach we design. This approach also uses phylogenetic relationships while inferring regulatory networks for a family of organisms. Using similar input information but designed in a very different framework, this transfer learning approach does not perform better than ProPhyC, which indicates that ProPhyC makes good use of the evolutionary information."
http://1.usa.gov/IVIIef

 
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Engineered networks of synthetic and natural proteins to control cell migration - ACS Synthetic Biology (ACS Publications)

Engineered networks of synthetic and natural proteins to control cell migration - ACS Synthetic Biology (ACS Publications) | SynBioFromLeukipposInstitute | Scoop.it

by
Evan Mills, Elizabeth Pham, Seema Nagaraj, and Kevin Truong
"Mammalian cells re-programmed with engineered transgenes have the potential to be useful therapeutic platforms because they can support large genetic networks, can be taken from a host or patient, and perform useful functions such as migration and secretion. Successful engineering of mammalian cells will require the development of modules that can perform well-defined, reliable functions, such as directed cell migration toward a chemical or physical signal. One inherently modular cellular pathway is the Ca2+ signaling pathway: protein modules that mobilize and respond to Ca2+ are combined across cell types to create complexity. We have designed a chimera of Rac1, a GTPase that controls cell morphology and migration, and calmodulin (CaM), a Ca2+-responsive protein, to control cell migration. The Rac1-CaM chimera (named RACer) controlled lamellipodia growth in response to Ca2+. RACer was combined with LOVS1K (a previously engineered light sensitive Ca2+-mobilizing module) and cytokine receptors to create protein networks where blue light and growth factors regulated cell morphology and thereby, cell migration. To show the generalizability of our design, we created a Cdc42-CaM chimera that controls filopodia growth in response to Ca2+. The insights that have been gained into Ca2+ signaling and cell migration will allow future work to combine engineered protein system to enable re-programmed cell-sensing of relevant therapeutic targets in vivo."

http://bit.ly/ImqYvf

 
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"Why join the navy, if you can be a pirate?"

Steve Jobs

 
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