SynBioFromLeukipposInstitute

By Lux Research 

"With synthetic biology (synbio) rapidly gaining momentum, and a landmark U.S. Supreme Court judgment striking down an age-old biological patenting system, biotechnology companies need to incorporate open-source into their innovation plans in order to succeed in the emerging landscape, according to Lux Research.

 Just as software patent battles are hobbling innovators like Google, Apple and Samsung in a multibillion-dollar morass, many classes of biotech patents are increasingly seen as a legally dubious, high-cost hindrance to innovation – as the Supreme Court acknowledged in its recent AMP vs. Myriad decision. But that’s not necessarily bad news for business or consumers. Alternatives to patents, like open-source computer code, standard protocols like GSM and HTML, and modular software have transformed information technology and accelerated product innovation in the space. Similarly, open-source genetic codes, such as modular DNA sequences, could hasten to market better drugs, biobased materials and useful organisms..."

 http://bit.ly/1fqIfyE

*What can biological computers be used for?* I am running a crowd funding campaign http://bit.ly/17dUxv8 to raise money (bit coins) and support (Tweets) for CytoComp, a biological computer As this concept might be new for many, I wish in the following to explain a bit what biological computer can be used to. I will in the following also make some posts to focus on certain diseases. *Potential applications of biological computers*Biological computers possess some distinct advantages over silicon computers . These systems can self-assemble and self- reproduce, which might provide some economic advantages. Moreover, cells can be engineered to sense and respond to environmental signals, even under extreme conditions such as high temperature, high pressure, radioactivity or toxic chemicals. Biological systems have the ability to adapt to new information from a changed environment.The ultimate goals of biocomputing are the monitoring and control of biological systems. *Monitoring of biological systems*Biological systems need to be monitored in respect to disease diagnostic, to drug screening, to understand experimental systems, and to observe the environment.In line with this, a biocomputer has been utilized to detect multiple disease indicators, such as mRNA of disease-related genes associated with small-cell lung cancer and prostate cancer. Moreover, they can be used in experimental models, such as conditional transgenes or inducible expression systems. Environmental monitoring is another interesting application. A cell based biosensor using logic gates has been used to detect arsenic, mercury and copper ion levels. *Control of biological systems*Biocomputers can potentially be used to control development, cell differentiation and re-programming, as all these processes depend on gene regulatory networks. Another application area is tissue engineering and tissue regeneration. Metabolic engineering has the potential to produce from simple, inexpensive starting materials a large number of chemicals that are currently derived from nonrenewable resources or limited natural resources. The metabolic flux can potentially be controlled by a biocomputer . Interesting might also be to control the immune system by a biocomputer, e.g. in transplantation medicine . An important application area is the control of malign growth. Some interesting experiments with logic based biological devices have been executed to detect cancer cells (e.g. small-cell lung cancer, prostate cancer, HeLa cells), and to induce selective apoptosis of these cells. Furthermore, biocomputers can be used to engineer context-dependent programmable drugs. A biocomputer with a context-sensing mechanism, which can simultaneously sense different types of molecules, has been engineered. In the future it might be used to detect a broad range of molecular disease symptoms, and react with the release of a drug molecule suitable for the treatment of the specific condition. In line with this concept a programmable NOR-based device has been developed capable of differentiating between prokaryotic cell strains based on their unique expression profile.

Ref: Moe-Behrens GHG (2013) The biological microprocessor, or how to build a computer with biological parts. Computational and Structural Biotechnology Journal. 7 (8): e201304003. This open-access article can be downloaded for free here http://bit.ly/1cwM43X ;

by

F. Ann Ran, Patrick D. Hsu, Chie-Yu Lin, Jonthan S. Gootenberg, Silvana Konermann, Alexandro E. Trevino, David A. Scott, Azusa Inoue, Shogo Matoba, Yi Zhang, Feng Zhang

"Targeted genome editing technologies have enabled a broad range of research and medical applications. The Cas9 nuclease from the microbial CRISPR-Cas system is targeted to specific genomic loci by a 20 nt guide sequence, which can tolerate certain mismatches to the DNA target and thereby promote undesired off-target mutagenesis. Here, we describe an approach that combines a Cas9 nickase mutant with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity, simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and extends the number of specifically recognized bases for target cleavage. We demonstrate that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency. This versatile strategy enables a wide variety of genome editing applications that require high specificity."

http://bit.ly/15r5dAg

 Thanks for your help so far for the CytoComp crowd funding campaign. CytoComp has jumped on place 4 on the Top10Social (Twitter)  Place 3 has just one Tweet more. It would be awesome, if you could help to change this. Please go to this page: http://cytocomp-bitstarter-mooc.herokuapp.com and push the Twitter button (maybe behind edX You ca follow the success on the leader board here: http://startupmooc.org 

by
Qingyang Liu  and Alexander Deiters

"Synthetic oligonucleotides have been extensively applied tocontrol a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson–Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanisms of biological processes, researchers need tools that allow for the perturbation of these processes with Nature’s precision.

 Light represents an excellent external regulatory element since irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photolabile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photoregulation of DNA function. Using this approach, we have both activated and deactivated gene expression optochemically at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations."

http://bit.ly/18o8p1e

The top 20 most influential people in synthetic biology http://bit.ly/1doauCu

by
Florian Lienert, Joseph P. Torella, Jan-Hung Chen, Michael Norsworthy, Ryan R. Richardson and Pamela A. Silver

"Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals."

http://bit.ly/14RgL4f

by
Melissa Hogenboom

"A UK team is building an "artificial" chromosome to be inserted into the world's first synthetic yeast.

Teams worldwide are making the other parts of its genome, which will be assembled to make the yeast strain Saccharomyces cerevisiae.

Once complete, new strains of synthetic yeast could help make products such as vaccines, biofuels and chemicals.

The UK government has announced a grant of almost £1m towards the project, which aims to be complete by 2017.

Synthetic biology involves assembling artificial genes to create new materials in a similar way that engineers build machines using many parts. Some even think it can form the basis of a new industrial revolution…"

http://bbc.in/19WeFk1

by
Hui Yang, Haoyi Wang, Chikdu S. Shivalila, Albert W. Cheng, Linyu Shi, Rudolf Jaenisch

"Highlights

One-step generation of mice with reporters in endogenous genesOne-step generation of conditional mutant miceOff-target analysis suggests high specificity of the CRISPR/Cas9 systemSummary The type II bacterial CRISPR/Cas system is a novel genome-engineering technology with the ease of multiplexed gene targeting. Here, we created reporter and conditional mutant mice by coinjection of zygotes with Cas9 mRNA and different guide RNAs (sgRNAs) as well as DNA vectors of different sizes. Using this one-step procedure we generated mice carrying a tag or a fluorescent reporter construct in the Nanog, the Sox2, and the Oct4 gene as well as Mecp2 conditional mutant mice. In addition, using sgRNAs targeting two separate sites in the Mecp2 gene, we produced mice harboring the predicted deletions of about 700 bps. Finally, we analyzed potential off-targets of five sgRNAs in gene-modified mice and ESC lines and identified off-target mutations in only rare instances."

http://bit.ly/1duolGz

Many people wish to contribute to the CytoComp crowd funding campaign http://cytocomp-bitstarter-mooc.herokuapp.com, but do not know how to use with Bitcoins. As this is a potential currency of the future, I wrote a brief introduction to Bitcoins: The basics about bitcoins BTC:  1) Get a bit coin account: go to this page https://coinbase.com and register (email and a password) That`s it.  2) Buy bit coins: http://howtobuybitcoins.info - lets you search your country more info:http://www.buybitcoinswiki.com/how-to-buy-bitcoins/ https://en.bitcoin.it/wiki/Buying_Bitcoins_(the_newbie_version) and if you are in the US coin base offers you instant bit coin purchase http://blog.coinbase.com/post/55203204550/instant-bitcoin-purchases-at-coinbase 3) BTC exchange rates:http://bitcoinity.org/markets 4) learn more (depending on your time): a) 2 min introduction https://www.weusecoins.com/en/ b) 10 min http://techcrunch.com/2013/04/11/bitcoin/ c) several hours https://www.secondmarket.com/education/learn/bitcoin-education-center d) several daysUdemyhttps://www.udemy.com/bitcoin-or-how-i-learned-to-stop-worrying-and-love-crypto/Khan Academy http://www.khanacademy.org/economics-finance-domain/core-finance/money-and-banking/bitcoin/v/bitcoin-what-is-it6 new bitcoin educational resourceshttp://www.forbes.com/sites/jonmatonis/2013/05/13/6-new-bitcoin-educational-resources/  ;

*Biology is the Technology of the Century*

"According to Pamela Silver, “if more than 10 percent of your experiments work, you’re doing the wrong experiments”—a sentiment that summarizes her overall philosophy of science. For Silver, it’s all about risk. Not only can big risk lead to big payoff (if you’re lucky), but it’s also where all the fun is. From her childhood in the then-fledgling Silicon Valley where she rubbed shoulders not only with technology luminaries but also with members of the Grateful Dead, to her current work as a pioneer in the field of synthetic biology, Silver’s career can be best described as one long pursuit of her scientific fascinations. Here, Silver discusses her approach to running a lab, her thoughts on the future of science, and why we should be able to engineer biology the same way we engineer electronics.  "
http://bit.ly/188Ejjt

Meet Pamela Silver 

at
#genobiotech13 

 November 21-23rd 2013 in Monterrey, Nuevo León, México.
http://bit.ly/1fjzMNK

I just got invited to give a talk about biological computing at an exiting conference with many great speakers:

#genobiotec

1 - Eric Davidson, California Institute of Technology.

2 - Pamela A. Silver, Harvard University
Designing Biological Systems for Health and Livability.

3 - James Ferrell, Stanford University
Bistability and trigger waves in the regulation of mitosis

4 - Julio Collado Vidés, Universidad Nacional Autónoma de México
Accelerating information access: challenges in genomics and the 21st century

5 - Mauricio Antunes, Colorado State University, Engineering synthetic sensing and signal transduction traits in plants

6 -  Octavio Mondragón-Palomino, Massachusetts Institute of Technology, Circuit design in synthetic biology

7 - J. Ruben Morones-Ramírez, Universidad Autónoma de Nuevo León

8 - Caroline Ajo-Franklin, Lawrence Berkeley National Laboratory, 

9 - Farren Isaacs, Yale University

10 - Peng Yin, Harvard University, Programming Nucleic Acids Self-Assembly

11 - Gerd Moe-Behrens, Leukippos Institute, CytoComp, The biological microprocessor, or how to build a computer with biological parts

PS the page get`s soon updated also with another speaker from Amyris 
--------------------------------------------------

13 Nov21-23 Monterrey,
Nuevo León,
 México.

 http://bit.ly/1fjzMNK

The BioBricks Foundation is now making all videos recorded and edited at SB6 available for FREE online

 http://bit.ly/10ohQxq   ;

by
Leroy Cronin

"In our laboratory we have been developing new approaches to discover the 'transition-to-evolvability' in chemistry. This is because we can discover or engineer an abiotic system that can evolve (we could define this as an inorganic chemical cell -ICHELL) we might be able to suggest that synthetic biology can exist in many chemical forms, of which the terrestrial biology found on planet earth is one subset."

 

http://bit.ly/1446XzQ