SynBioFromLeukipposInstitute

"Britain's legacy of nuclear waste dates back 60 plus years and a long term solution to deal with it hasn't yet been found. After this week's announcement that the UK will have a new nuclear power station, Hinkley C in Somerset, Dr Adam Rutherford asks Professor Sue Ion, former Director of Technology at British Nuclear Fuels and Chair of the European Commission's Science and Technology Committee, Euratom, how much extra waste this new plant will add to the radioactive stockpile.

Eighteen years ago the first planet outside of our solar system was discovered, "51 Pegasi b". This week the tally of exoplanets passed one thousand, and as astronomer Dr Stuart Clark tells Adam, an earth twin isn't part of the planetary list.....yet.

Show Us Your Instrument: Public Astronomer Dr Marek Kukula introduces the original Six Pip Masterclock at the Greenwich Observatory. This clock was used in the 1920s to send the time signals down a telephone line to the BBC, for transmission to the whole country over the radio. That's not the case now, and Adam goes down into the basement of Broadcasting House in London in search of the atomic clock that's now used to generate the Greenwich Time Signal and the famous BBC pips.

iGEM is a global biology competition that allows students to build their own organisms. The UK has two teams going to the grand final next week. Adam goes to meet the team from Imperial College London, who have made a bacterium which produces plastic."

http://bbc.in/1cgk2z6

by
Ryan Bethencourt 

"What is biocoding? For those of you who have been following the biotechnology industry, you’ll have heard of the rapid advances in genome sequencing. Our ability to read the language of life has advanced dramatically, but only recently have we been able to start writing the language of life at scale.

 The first large-scale biocoding success was in 2010, when Craig Venter (one of my scientific heroes) wrote up the genome of an entirely synthetic organism, booted it up and created de novo life. Venter’s new book, Life at the Speed of Light, discusses the creation of the first synthetic life form. In his book and in video interviews, Venter talks about the importance of ensuring the accuracy of the DNA code they designed. One small deletion of a base (one of the four letters that make up the biological equivalent of 1s and 0s) resulted in a reading frame shift that left them with gibberish genomes, a mistake they were able to find and correct. One of the most amusing parts of Venter’s work was that they were able to encode sequences in the DNA to represent each letter of the English alphabet. Their watermark included the names of their collaborators, famous quotes, an explanation of the coding system used, and a URL for those who crack the code written in the DNA. Welcome to the future — and let me know if you crack the code! Biocoding is just the beginning of the rise of the true biohackers. This is a community of several thousand people, with skill sets ranging from self-taught software hackers to biology postdocs who are impatient with the structure of traditional lab work. Biohackers want to tinker; do fun science; and, in the process, accelerate the pace of biotech innovation. There are plenty of differences between writing computer code and writing code in the building blocks of life, but the important thing is that it can be done and is being done now by citizen scientists working both from shared biohacker labs (like Biocurious, Genspace, and Counter Culture Labs) and at home (for example, Cathal Garvey, who works out of a spare bedroom in his mother’s home). Drew Endy’s short video about Engineering Biology gives a great overview of what we can accomplish when we start programming the genetic code. One of his projects is genetically encoded data storage — but it’s not just about replacing dry silicon with wet carbon; it’s about what can happen when you can do computing in an environment where you couldn’t possibly place silicon: inside a living cell. Biotech is the wet nanotech we’ve been waiting for. It’s a little less logical and a lot buggier than we’d like, but we now have the tools to write DNA, insert this code into a cell, reboot the cell and make those cells produce custom-designed proteins and substances, and engineer biology. The potential for synthetic biology and biotechnology is vast. The biocoding era will be as transformative as the computer era, and we all have an opportunity to create the future together. Biocoder is a new O’Reilly quarterly newsletter chronicling the rise of DIY bio, synthetic bio, biohackers, Grinders, and the new innovations being developed at the edges of the biotech industry. Check out Biocoder and download it for free."

 http://oreil.ly/16tARi5

http://bit.ly/1aECsmk

http://bit.ly/17wD4cM

by
Matthew Swayne

"Synthetic life could create real benefits.

For more than half a century scientists have looked on the DNA molecule as life's blueprint. Now biological engineers are beginning to see the molecule not as a static plan, but more like a snippet of life's computer code that they can program.

Penn State researchers are unraveling the mystery of how nature codes and recodes this program to address some of the world's biggest challenges, says Howard Salis, assistant professor of biological engineering and chemical engineering.

"You can engineer DNA to reprogram the metabolism of simple organisms and you can program them to make what you want, or to make it more efficiently, says Salis. "The trick is to understand how the organism interprets its DNA, and then to optimize new DNA sequences to rationally control its behavior."

This rapidly developing field, often referred to as synthetic biology, may one day allow biological engineers to design living systems just as reliably as engineers currently design and build airplanes, cars and trains, according to Salis. It also holds the key to products such as inexpensive biofuels, environmentally friendly plastics, and less expensive pharmaceuticals.

"Decoding the function of DNA -- what the DNA makes the organism do -- and then recoding it with a new human-desired function is central to synthetic biology," he says…"

BioCoder is a quarterly newsletter for DIYbio, synthetic bio, and anything related http://oreil.ly/165CFmA

by

Jessica Stoller-Conrad

"

Embracing the idea that molecules can be programmed much like a computer, researchers can now perform remarkable feats on a very small scale. New Caltech faculty member Lulu Qian, assistant professor of bioengineering, performs research in the field of molecular programming because it allows her to design synthetic molecular systems with neural-network-like behaviors and tiny robots, both from the programmed interactions of DNA molecules. Originally from Nanjing, China, Qian received her bachelor's degree from Southeast University in 2002 and her PhD from Shanghai Jiao Tong University in 2007. After working as a postdoctoral scholar at Caltech in the laboratory of Shuki Bruck, Qian became a visiting fellow at Harvard University; she returned to Caltech and joined the faculty in July. Recently, Qian answered a few questions about her research, and how it feels to be back at Caltech.

What do you work on?

I work on rationally designing and creating molecular systems with programmable behaviors. I am interested in programming biological molecules—like DNA and RNA—to recognize molecular events from the biochemical environment, process information, make decisions, take actions, and to learn and evolve. Molecular programming is not just about using computer programs to aid the design and analysis of molecular systems; it is more about adapting the principles of computer science to create biochemical systems that can carry out instructions to perform tasks at the molecular level. For example, I develop simple and standard molecular components that can be used to perform a variety of tasks and systematic ways to configure the behavior of interacting molecules to carry out one computational or mechanical task or another. These custom-designed molecules can be ordered from a commercial supplier and mixed in a test tube to generate a "molecular program." 

Using this approach, I have designed DNA circuits that can solve basic logic problems, and I have constructed a DNA neural network that can perform simple associative memory functions—much like a network of neurons in the brain, though in a rudimentary way. In my future research, I would like to improve the speed, robustness, and complexity of these implementations and to explore the possibility of creating molecular systems with learning capabilities, while also beginning new work in the field of molecular robots—tiny, nanoscale machines made of DNA that can perform a designed task such as sorting cargo or solving a maze.

What do you find most exciting about your research?

I am driven by curiosity—outside of the lab, I like Legos and puzzles—and I view life as a program, one that is much more sophisticated than any other program that we know of so far. The sequence of nucleotides that make up DNA—As, Ts, Cs, and Gs—encodes the program within a genome, orchestrating molecules to sense, to compute, to respond, and to grow. Because of their different lengths and sequences, one genome produces a bacterium while another produces a plant, or an insect, or a mammal. The genetic program describes how to make molecules, and molecules are machines that can achieve complex tasks to regulate the behaviors of individual cells. To better appreciate the molecular programs that nature creates, I want to understand what possible behaviors a network of interacting molecules can exhibit and how we can rationally design such behaviors.

But, I am also driven by my engineering nature. I want to design and build molecular systems with increasing complexity and sophistication. For example, you could imagine using such molecular machines to make a nanoscale factory that manufactures novel chemicals in a test tube. These chemicals could become new materials or new drugs. You could also imagine embedding such molecular machines into individual cells so that you could collect information from the molecular environment and regulate the cell's behavior. Such regulation could lead to responsive biosynthesis—the production of proteins or other molecules in response to a stimulus—or localized diagnostics followed by therapeutics.

How did you get into your field?

I started programming computers when I was 13 years old, and I have loved it ever since then. My dad was a philosopher, and because of his influence, I got curious about fundamental questions such as who I am and why I think the way that I do. At first, I tried to look for these answers in molecular biology, but as a programmer, biology was difficult for me to understand. Unlike in programming, you cannot just define a few logical principles to understand the behavior of an entire biological system or organism. At the time, biology was not as fun for me—or as logical—as computer programming.

But just before I went to graduate school, I discovered the first publication in DNA computing by Len Adleman at the University of Southern California. He used DNA molecules as a computing substrate to solve a hard math problem. The moment that I finished reading this paper, I felt completely excited. It was the first time that I saw a strong relationship between molecules that are traditionally only used in biology—like DNA and RNA—and computer programming. That was when I started working in my field.   

Why are you excited to be at Caltech?

After working at other institutions, Caltech has been a very special place for me. I like that Caltech is small and is an environment in which we're encouraged to pursue fundamental research and appreciate the beauty of science. I am most excited about doing great science here. There are very talented students—I am looking for the most fun and creative minds to join my lab—and I have visionary colleagues. We have an excellent molecular programming community at Caltech, including Erik Winfree in computer science, Shuki Bruck in electrical engineering, Richard Murray in control and dynamical systems, Niles Pierce and Paul Rothemund in bioengineering, and now myself. And we now have this new division, Biology and Biological Engineering, which I believe will bring fundamental engineering to biological sciences and create interdisciplinary research activities.

- See more at: http://www.caltech.edu/content/programming-dna-molecular-robots-interview-lulu-qian#sthash.NSli3vtS.dpuf";

http://bit.ly/17ci8LK

by
Belen Calles and Víctor de Lorenzo 

"The σ54-dependent prokaryotic regulator XylR implements a one-input/one-output actuator that transduces the presence of the aromatic effector m-xylene into transcriptional activation of the cognate promoter Pu. Such a signal conversion involves the effector-mediated release of the intramolecular repression of the N-terminal A domain on the central C module of XylR. On this background, we set out to endow this regulator with additional signal-sensing capabilities by inserting a target site of the viral protease NIa in permissive protein locations that once cleaved in vivo could either terminate XylR activity or generate an effector-independent, constitutive transcription factor. To find optimal protein positions to this end, we saturated the xylR gene DNA with a synthetic transposable element designed for randomly delivering in-frame polypeptides throughout the sequence of any given protein. This Tn5-based system supplies the target gene with insertions of a selectable marker that can later be excised, leaving behind the desired (poly) peptides grafted into the protein structure. Implementation of such knock-in-leave-behind (KILB) method to XylR was instrumental to produce a number of variants of this transcription factor (TF) that could compute in vivo two inputs (m-xylene and protease) into a single output following a logic that was dependent on the site of the insertion of the NIa target sequence in the TF. Such NIa-sensitive XylR specimens afforded the design of novel regulatory nodes that entered protease expression as one of the signals recognized in vivo for controlling Pu. This approach is bound to facilitate the functionalization of TFs and other proteins with new traits, especially when their forward engineering is made difficult by, for example, the absence of structural data…."

http://bit.ly/17JcT2P

by
April Flowers 

"A team of scientists from Harvard and Yale have recorded the entire genome of the bacteria E. coli, and in a dramatic demonstration of the potential of rewriting an organism’s genetic code, they have improved the bacterium’s ability to resist viruses.

 “This is the first time the genetic code has been fundamentally changed,” according to Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale. “Creating an organism with a new genetic code has allowed us to expand the scope of biological function in a number of powerful ways.” Creating this genomically recoded organism raises the possibility that future researchers might be able to retool nature and create potent new proteins to accomplish a wide variety of purposes — from combating disease to generating new classes of materials. The findings from this groundbreaking study, which changes the rules of biology, were published in Science. Isaacs and co-author George Church of Harvard Medical School led this research, which is a product of years of studies in the emerging field of synthetic biology, which seeks to re-design natural biological systems for useful purposes. Encoded by DNA’s instructional manual and made up of 20 amino acids, proteins carry out various important functional roles in the cell. A full set of 64 triplet combinations of the four nucleic acids that comprise the backbone of DNA encode amino acids. Triplets are sets of three nucleotides, called codons, and they are the genetic alphabet of life. For this study, the research team examined the possibility of expanding upon nature’s handywork by substituting different codons or letters throughout the genome and then reintroducing entirely new letters to create amino acids not found in nature. This landmark study represents the first time that the genetic code has been completely changed across an organism’s genome. The research team first swapped all 321 instances of a specific codon, or “genetic three-letter word,” in E. coli for a supposedly identical word. Then they recoded the original word with a new meaning and new amino acid to eliminate its natural stop sign that terminates protein production. This novel genome allowed the bacteria to resist viral infection by limiting the production of natural proteins that viruses use to infect cells. They then converted the “stop” codon into one that encodes new amino acids, inserted it into the genome in a sort of “plug and play” fashion. The results set the stage for using the recoded E. coli as a living foundry, capable of biomanufacturing new classes of “exotic” proteins and polymers. The recoded molecules could be the foundation for a new generation of materials, nanostructures, therapeutics, and drug delivery vehicles, Isaacs said. “Since the genetic code is universal, it raises the prospect of recoding genomes of other organisms,” Isaacs said. “This has tremendous implications in the biotechnology industry and could open entirely new avenues of research and applications.”…."

http://bit.ly/17CvXQi

by
María Abad,Lluc Mosteiro,Cristina Pantoja,Marta Cañamero,Teresa Rayon,Inmaculada Ors,Osvaldo Graña,Diego Megías,Orlando Domínguez,Dolores Martínez,Miguel Manzanares,Sagrario Ortega& Manuel Serrano

"Reprogramming of adult cells to generate induced pluripotent stem cells (iPS cells) has opened new therapeutic opportunities; however, little is known about the possibility of in vivo reprogramming within tissues. Here we show that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney reveal groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, we demonstrate that haematopoietic cells can also be reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells in the blood and, at the transcriptome level, these in vivo generated iPS cells are closer to embryonic stem cells (ES cells) than standard in vitro generated iPS cells. Moreover, in vivo iPS cells efficiently contribute to the trophectoderm lineage, suggesting that they achieve a more plastic or primitive state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic markers. We conclude that reprogramming in vivo is feasible and confers totipotency features absent in standard iPS or ES cells. These discoveries could be relevant for future applications of reprogramming in regenerative medicine."


http://bit.ly/1gqWvgQ

by
Denisa Kera

"Highlights

• Novel forms of public engagement in bio and nanotechnologies in the DIYbio and Hackerspaces.

• Decentralized, participatory, and design oriented practices based on open science and open access paradigms.
•Alternative R&D approaches bring experimental forms of ethical deliberation and regulation.
AbstractTypically nanotechnology and synthetic biology are discussed in terms of novel life forms and materials created in laboratories, or by novel convergences of technologies (ICTs and biological protocols) and science paradigms (engineering and biology) they initiated. Equally inspiring is their ability to generate novel institutions and global communities around emergent sciences, which radicalize the forms of public engagement and ethical deliberation. We are starting to witness alternative (iGEM competitions) and almost underground R&D engagements with Synthetic Biology (DIYbio movement), which inspired the emerging bottom-up involvements in nanotechnologies in projects, such as the NanoSmanoLab in Slovenia. These bottom-up involvements use tinkering and design as models for both research and public engagement. They democratize science and initiate a type of grassroots “science diplomacy”, supporting research in developing countries. We will discuss several recent examples, which demonstrate these novel networks (“Gene gun” project by Rüdiger Trojok from the Copenhagen based hackerspace, Labitat.dk, the “Bioluminescence Project” by Patrik D'haeseleer from Biocurious biotech hackerspace in Sunnyvale, CA, and the “Biodesign for the real world” project by members of the Hackteria.org). They all use design prototypes to enable collaborative and global tinkering, in which science and community are brought together in open biology laboratories and DIYbio hackerspaces, such as Hackteria.org or Biocurious. In these projects research protocols encompass broader innovative, social and ethical norms. Hackerspaces represent a unique opportunity for a more inclusive, experimental, and participatory policy that supports both public and global involvements in emergent scientific fields....

"
http://bit.ly/1aOnQ5p

by
Timothy S Gardner, Kristy Hawkins

"In this article, we relate the story of Synthetic Biology's birth, from the perspective of a co-founder, and consider its original premise — that standardization and abstraction of biological components will unlock the full potential of biological engineering. The standardization ideas of Synthetic Biology emerged in the late 1990s from a convergence of research on cellular computing, and were motivated by an array of applications from tissue regeneration to bio-sensing to mathematical programming. As the definition of Synthetic Biology has grown to be synonymous with Biological Engineering and Biotechnology, the field has lost sight of the fact that its founding premise has not yet been validated. While the value of standardization has been proven in many other engineering disciplines, none of them involve self-replicating systems. The engineering of self-replicating systems will likely benefit from standardization, and also by embracing the forces of evolution that inexorably shape such systems."

http://bit.ly/19Sm9Y8

by
Kyung-Ho Lee, Dr. Dong-Myung Kim

"Synthetic biology is built on the synthesis, engineering, and assembly of biological parts. Proteins are the first components considered for the construction of systems with designed biological functions because proteins carry out most of the biological functions and chemical reactions inside cells. Protein synthesis is considered to comprise the most basic levels of the hierarchical structure of synthetic biology. Cell-free protein synthesis has emerged as a powerful technology that can potentially transform the concept of bioprocesses. With the ability to harness the synthetic power of biology without many of the constraints of cell-based systems, cell-free protein synthesis enables the rapid creation of protein molecules from diverse sources of genetic information. Cell-free protein synthesis is virtually free from the intrinsic constraints of cell-based methods and offers greater flexibility in system design and manipulability of biological synthetic machinery. Among its potential applications, cell-free protein synthesis can be combined with various man-made devices for rapid functional analysis of genomic sequences. This review covers recent efforts to integrate cell-free protein synthesis with various reaction devices and analytical platforms."


http://bit.ly/GWXcyp