SynBioFromLeukipposInstitute

by

Elani Y, Demello AJ, Niu X, Ces O.

"Droplet interface bilayer (DIB) networks have vast potential in the field of membrane biophysics, synthetic biology, and functional bio-electronics. However a technological bottleneck exists in network fabrication: existing methods are limited in terms of their automation, throughput, versatility, and ability to form well-defined 3-D networks. We have developed a series of novel and low-cost methodologies which address these limitations. The first involves building DIB networks around the contours of a microfluidic chip. The second uses flow rate and droplet size control to influence droplet packing geometries within a microfluidic chamber. The latter method enables the controlled formation of various 3-D network arrays consisting of thousands of interconnected symmetric and asymmetric lipid bilayers for the first time. Both approaches allow individual droplet position and composition to be controlled, paving the way for complex on-chip functional network synthesis."

http://1.usa.gov/N60Oya

by

Christof Koch

"It has been argued that the technological capability to fully simulate the human brain on digital computers will exist within a decade. This is taken to imply that we will comprehend its functioning, eliminate all diseases, and “upload” ourselves to computers (1). Although such predictions excite the imagination, they are not based on a sound assessment of the complexity of living systems. Such systems are characterized by large numbers of highly heterogeneous components, be they genes, proteins, or cells. These components interact causally in myriad ways across a very large spectrum of space-time, from nanometers to meters and from microseconds to years. A complete understanding of these systems demands that a large fraction of these interactions be experimentally or computationally probed. This is very difficult."

http://bit.ly/RrY5x4

by

Mark Isalan

"The small genomes of some bacteria could provide the first complete understanding of a biological system. A new computer model brings this goal closer, by calculating every process in a dividing Mycoplasma cell...."

http://bit.ly/OMmShb

Podcast: Today Zach and Kelly talk to Dr. Jordan Miller, a postdoctoral student in Dr. Christopher Chen’s Tissue Microfabrication Lab at the University of Pennsylvania, about his recent breakthrough using 3D printing to create blood vessels.

comment on: Khalil AS, Lu TK, Bashor CJ, Ramirez CL, Pyenson NC, Joung JK and Collins JJ. A synthetic biology framework for programming eukaryotic transcription functions. Cell 150: 647-658 (2012).

PDF can be found here: http://www.bu.edu/abl/files/cell_khalil.pdf
http://bit.ly/MmoVo1

Our electronic devices are getting smaller and smaller while doing more and more, so much so that we will soon reach the practical limit of current materials. The electronics of tomorrow require alternatives, such as nanowires made of DNA that can serve as conductive paths and nanotransistors for miniature circuits. In the journal Angewandte Chemie, German scientists have now described a new method for the production of stable, conducting DNA nanowires.

 http://bit.ly/Oy5DRb

Important paper!

*A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions*

by
Ahmad S. Khalil, Timothy K. Lu, Caleb J. Bashor, Cherie L. Ramirez, Nora C. Pyenson, J. Keith Joung, James J. Collins

*Highlights*
- Zinc fingers can be used to wire orthogonal connections in yeast synthetic circuits
- Zinc finger TF design permits adjustable component properties for modulating outputs
- Protein-protein interactions can be used to engineer cooperativity in zinc finger TFs
- TF component properties can be combinatorially adjusted to reshape signal integration

*Summary*
Eukaryotic transcription factors (TFs) perform complex and combinatorial functions within transcriptional networks. Here, we present a synthetic framework for systematically constructing eukaryotic transcription functions using artificial zinc fingers, modular DNA-binding domains found within many eukaryotic TFs. Utilizing this platform, we construct a library of orthogonal synthetic transcription factors (sTFs) and use these to wire synthetic transcriptional circuits in yeast. We engineer complex functions, such as tunable output strength and transcriptional cooperativity, by rationally adjusting a decomposed set of key component properties, e.g., DNA specificity, affinity, promoter design, protein-protein interactions. We show that subtle perturbations to these properties can transform an individual sTF between distinct roles (activator, cooperative factor, inhibitory factor) within a transcriptional complex, thus drastically altering the signal processing behavior of multi-input systems. This platform provides new genetic components for synthetic biology and enables bottom-up approaches to understanding the design principles of eukaryotic transcriptional complexes and networks."

http://bit.ly/MBzzZD

Comment
*Researchers expand synthetic biology's toolkit: New method could enable reprogramming of mammalian cells*

"Through the assembly of genetic components into "circuits" that perform logical operations in living cells, synthetic biologists aim to artificially empower cells to solve critical problems in medicine, energy and the environment. To succeed, however, they'll need far more reliable genetic components than the small number of "off-the-shelf" bacterial parts now available.
Now a new method developed by Boston University biomedical engineers Ahmad S. Khalil and James J. Collins -- and collaborators at Harvard Medical School, Massachusetts General Hospital and MIT -- could significantly increase the number of genetic components in synthetic biologists' toolkit and, as a result, the size and complexity of the genetic circuits they can build. The development could dramatically enhance their efforts not only to understand how biological organisms behave and develop, but also to reprogram them for a variety of practical applications. Described in the August 2 online edition of Cell, the method offers a new paradigm for constructing and analyzing genetic circuits in eukaryotes -- or organisms whose cells contain nuclei, which include everything from yeasts to humans. Instead of constructing these circuits with off-the-shelf parts from bacteria and porting them into eukaryotes, as most synthetic biologists do, Khalil and his collaborators have engineered these circuits using modular, functional parts from the eukaryotes themselves...."
http://bit.ly/Np2iiF

PDF: http://bit.ly/Quzry8

by

A. Goldbeter, C. Gérard, D. Gonze, J.C. Leloup, G. Dupont

"Rhythms abound in biological systems, particularly at the cellular level where they originate from the feedback loops present in regulatory networks. Cellular rhythms can be investigated both by experimental and modeling approaches, and thus represent a prototypic field of research for systems biology. They have also become a major topic in synthetic biology. We review advances in the study of cellular rhythms of biochemical rather than electrical origin by considering a variety of oscillatory processes such as Ca++ oscillations, circadian rhythms, the segmentation clock, oscillations in p53 and NF-κB, synthetic oscillators, and the oscillatory dynamics of cyclin-dependent kinases driving the cell cycle. Finally we discuss the coupling between cellular rhythms and their robustness with respect to molecular noise."
http://bit.ly/OkcQ7e