SynBioFromLeukipposInstitute

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Evan J Olson & Jeffrey J Tabor

"Systems biologists aim to understand how organism-level processes, such as differentiation and multicellular development, are encoded in DNA. Conversely, synthetic biologists aim to program systems-level biological processes, such as engineered tissue growth, by writing artificial DNA sequences. To achieve their goals, these groups have adapted a hierarchical electrical engineering framework that can be applied in the forward direction to design complex biological systems or in the reverse direction to analyze evolved networks. Despite much progress, this framework has been limited by an inability to directly and dynamically characterize biological components in the varied contexts of living cells. Recently, two optogenetic methods for programming custom gene expression and protein localization signals have been developed and used to reveal fundamentally new information about biological components that respond to those signals. This basic dynamic characterization approach will be a major enabling technology in synthetic and systems biology."


 bit.ly/SV3C6G

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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

http://bit.ly/1naf7iH

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D. Ewen Cameron, Caleb J. Bashor and James J. Collins

"The ability to rationally engineer microorganisms has been a long-envisioned goal dating back more than a half-century. With the genomics revolution and rise of systems biology in the 1990s came the development of a rigorous engineering discipline to create, control and programme cellular behaviour. The resulting field, known as synthetic biology, has undergone dramatic growth throughout the past decade and is poised to transform biotechnology and medicine. This Timeline article charts the technological and cultural lifetime of synthetic biology, with an emphasis on key breakthroughs and future challenges."

http://bit.ly/1kHBEBV

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Christina Agapakis 

"According to the New York Times, synthetic biology is creating DNA out of thin air. A recent article about synthetic biology and consumer goods describes DNA synthesis as a process where “DNA is created on computers and inserted into organisms.” Computers are pretty cool and really useful in synthetic biology labs, but it takes a lot more than a computer to turn a text file full of A’s T’s C’s and G’s into DNA.

http://bit.ly/1nGXQkr

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 http://bit.ly/1qyVPaW

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Mark Thomas Smith, Kristen M. Wilding, Jeremy M. Hunt, Anthony M. Bennett, Bradley C. Bundy

"The engineering of and master over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology."

 http://bit.ly/1pF35Em

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Jeffrey C. Way, James J. Collins, Jay D. Keasling, and Pamela A. Silver

"Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standard- ized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field’s accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering."

http://bit.ly/1pC96Se

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Wendisch VF.

"Amino acids are produced at the multi-million-ton-scale with fermentative production of l-glutamate and l-lysine alone being estimated to amount to more than five million tons in the year 2013. Metabolic engineering constantly improves productivities of amino acid producing strains, mainly Corynebacterium glutamicum and Escherichia coli strains. Classical mutagenesis and screening have been accelerated by combination with intracellular metabolite sensing. Synthetic biology approaches have allowed access to new carbon sources to realize a flexible feedstock concept. Moreover, new pathways for amino acid production as well as fermentative production of non-native compounds derived from amino acids or their metabolic precursors were developed. These include dipeptides, α,ω-diamines, α,ω-diacids, keto acids, acetylated amino acids and ω-amino acids."

 http://bit.ly/1nBUSO3

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Pietro Genovese, Giulia Schiroli, Giulia Escobar, Tiziano Di Tomaso,Claudia Firrito, Andrea Calabria, Davide Moi, Roberta Mazzieri, Chiara Bonini, Michael C. Holmes, Philip D. Gregory, Mirjam van der Burg,Bernhard Gentner, Eugenio Montini, Angelo Lombardo & Luigi Naldini

"Targeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene transfer and limited proficiency of the homology-directed DNA repair pathway constrain gene targeting in human HSCs. By tailoring delivery platforms and culture conditions we overcame these barriers and provide stringent evidence of targeted integration in human HSCs by long-term multilineage repopulation of transplanted mice. We demonstrate the therapeutic potential of our strategy by targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy donors and a subject with X-linked severe combined immunodeficiency (SCID-X1). Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional lymphoid cells that possess a selective growth advantage over those carrying disruptive IL2RG mutations. These results open up new avenues for treating SCID-X1 and other diseases."


 http://bit.ly/1jnl7U2