SynBioFromLeukipposInstitute

by

Tore Dehli, Christian Solem and Peter Ruhdal Jensen

"Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression levels using libraries of synthetic promoters now exist."
http://bit.ly/RXfkre

http://1.usa.gov/VzcuiP

http://bit.ly/T8lWBX

by

Wang J, Xiong Z, Meng H, Wang Y, Wang Y.

"As a discipline to design and construct organisms with desired properties, synthetic biology has generated rapid progresses in the last decade. Combined synthetic biology with the traditional process, a new universal workflow for drug development has been becoming more and more attractive. The new methodology exhibits more efficient and inexpensive comparing to traditional methods in every aspect, such as new compounds discovery & screening, process design & drug manufacturing. This article reviews the application of synthetic biology in antibiotics development, including new drug discovery and screening, combinatorial biosynthesis to generate more analogues and heterologous expression of biosynthetic gene clusters with systematic engineering the recombinant microbial systems for large scale production."

http://1.usa.gov/RdVHw6

 http://bit.ly/S4d2ag

http://1.usa.gov/Tj6HMN

http://bit.ly/R0nez8

by

Chen D, Arkin AP.

"Natural biological systems have evolved a diverse array of switches to realize their strategies for environmental response and development. Emerging applications of synthetic biology have begun to exploit such switches to achieve increasingly sophisticated designed behaviors. However, not all switch architectures allow facile design of the switching and memory properties. Furthermore, not all designs are built from components for which large families of variants exist, a requirement for building many orthogonal switch variants. Therefore, there is a critical need from genetic engineers for scalable strategies that yield custom bistable switches. Here, we use a sigma factor and its cognate anti-sigma factor to experimentally verify that ultrasensitivity from sequestration combined with positive feedback is sufficient to build a bistable switch. We show that sequestration allows us to predictably tune the switching boundaries, and we can easily tune our switch to function as a set-reset latch that can be toggled between two states by a pulse of inducer input."

http://1.usa.gov/Tz3kBB

http://1.usa.gov/QDzlnI

by

Amit R.

"One of the greatest challenges facing synthetic biology is to develop a technology that allows gene regulatory circuits in microbes to integrate multiple inputs or stimuli using a small DNA sequence "foot-print", and which will generate precise and reproducible outcomes. Achieving this goal is hindered by the routine utilization of the commonplace σ(70) promoters in gene-regulatory circuits. These promoters typically are not capable of integrating binding of more than two or three transcription factors in natural examples, which has limited the field to developing integrated circuits made of two-input biological "logic" gates. In natural examples the regulatory elements, which integrate multiple inputs are called enhancers. These regulatory elements are ubiquitous in all organisms in the tree of life, and interestingly metazoan and bacterial enhancers are significantly more similar in terms of both Transcription Factor binding site arrangement and biological function than previously thought. These similarities imply that there may be underlying enhancer design principles or grammar rules by which one can engineer novel gene regulatory circuits. However, at present our current understanding of enhancer structure-function relationship in all organisms is limited, thus preventing us from using these objects routinely in synthetic biology application. In order to alleviate this problem, in this book chapter, I will review our current view of bacterial enhancers, allowing us to first highlight the potential of enhancers to be a game-changing tool in synthetic biology application, and subsequently to draw a road-map for developing the necessary quantitative understanding to reach this goal."

by

Dehli T, Solem C, Jensen PR.

"Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression levels using libraries of synthetic promoters now exist."

http://1.usa.gov/XC0TwC

http://bit.ly/PGh4Jt