SynBioFromLeukipposInstitute

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Ariadna Martos, Mercedes Jiménez, Germán Rivas, Petra Schwille

"The components of the bacterial division machinery assemble to form a dynamic ring at mid-cell that drives cytokinesis. The nature of most division proteins and their assembly pathway is known. Our knowledge about the biochemical activities and protein interactions of some key division elements, including those responsible for correct ring positioning, has progressed considerably during the past decade. These developments, together with new imaging and membrane reconstitution technologies, have triggered the ‘bottom-up’ synthetic approach aiming at reconstructing bacterial division in the test tube, which is required to support conclusions derived from cellular and molecular analysis. Here, we describe recent advances in reconstituting Escherichia coli minimal systems able to reproduce essential functions, such as the initial steps of division (proto-ring assembly) and one of the main positioning mechanisms (Min oscillating system), and discuss future perspectives and experimental challenges."

http://bit.ly/10uFvL3

by

Wendell A. Lim , Rebecca Alvania and Wallace F. Marshall

"‘Verum esse ipsum factum’, the true is in the made – Giambattista Vico

Synthetic Cell Biology sounds intriguing, but the name begs the question – why should we try to rebuild or reprogram the cell, especially when we barely understand how cells work? This issue of TiCB explores this emerging area in which scientists are taking apart, rebuilding, reprogramming, and repurposing parts of the cell. The reviews cover a wide range of scales, from microscopic molecular machines to macroscopic, multicellular tissues. These reviews highlight the fact that, in addition to its role in harnessing and unleashing the power of cells for new and future applications, synthetic biology also has an important role to play in facilitating the understanding of complex cellular processes. In short, we can learn much about cells through the process of trying to build them (or parts of them). And if we understand cells, we can start to really harness their power.

Cell biology has historically been primarily an observational science, inextricably linked with tools like the microscope, which first enabled humans to peer into the remarkable world of the cell, with its diversity of forms and complex and dynamic inner structure. Yet today, even as we know the genomic parts list of the cell, we realize that there is a huge gap in our mechanistic understanding of the logic of how these systems work. On the one hand, we can observe these beautiful systems that yield complex cellular structures, movements, and regulatory decisions; on the other, we have a list of molecular parts that somehow underlie these behaviors and decisions. But the middle ground linking how these parts fit together and work as a system is often missing. We have a serious gap in the mesoscopic mechanistic understanding of how microscopic molecules work together to yield complex macroscopic behavior.

Synthetic biology as applied to cell biology can help to address this gap, because in many ways it is a philosophical descendant of old-school reconstitution biochemistry. It offers a unique and powerful way to construct simple, stripped down, and manipulable molecular systems, which can then be used gain insight into the fundamental rules of how some complex biological process takes place. But now, thanks to the power of genetic engineering, much of this manipulation and perturbation of systems can take place in the milieu of the living cell, with its basic metabolic and transcriptional systems and complex spatial environments. The cell, or even artificially constructed cells, can serve as the new test tube for logical and systematic analysis of a process. As Vico first suggested (and Richard Feynman later reiterated), if we can build it, we can understand it.

Predictive, mechanistic understanding of how the parts of a cell work together to generate cell behaviors is not only interesting in its own right; it would provide a rational basis to turn cell biology into an engineering discipline. Synthetic cell biology has the promise of remarkable biotechnology applications. Many advances have been made in harnessing cells to create new and useful molecules, by cobbling together new strings of metabolic enzymes. But in many ways, this is only the tip of the iceberg of what cells could do. Current efforts have largely ignored the cell, its structure and regulation, as a tool to harness. Cells are some of the most powerful and capable devices we know, especially in producing complex products. Manipulation of cellular organelles, transport systems, and secretion systems and their regulation could, if properly applied, have dramatic effects on cell-based production of fuels, drugs, nutrients, and chemicals. Ultimately, learning how to reprogram the machinery of the cell extends far beyond biofermentation – it may lead to dramatic advances in designer cells (or cell-inspired devices) that can execute precision therapeutic or regenerative functions. It may even be possible to create new cells that have hybrid functions and structures that are completely novel. The next few decades offer tantalizing promise of how our understanding of cell biology could be applied, and it is time for cell biologists to start thinking creatively about how cells as machines could be harnessed..."

http://bit.ly/TfRAlP

By Crystal Gammon

"When researchers synthesized the poliovirus from scratch 10 years ago, it was a major feat in the rapidly growing field of synthetic biology. For the first time, scientists had chemically stitched together bits of DNA to create a functional virus without the guidance of a biological template.

Now the virologist who led that team, Eckard Wimmer of Stony Brook University, continues to push the field by constructing designer viruses and, potentially, designer vaccines. New York Genome Center spoke with Wimmer recently about the future of synthetic biology.

Q: What's the most important thing we can gain from designer viruses?

A: We’re developing pretty good candidates for new vaccines. Current vaccines, such as influenza, often don't work well in old folks, for example, so we’ve set out to make new ones.

With conventional molecular biology methods, you cannot make radically changed viral genomes. It’s very tedious. But when we work with computer scientists to synthesize a virus, we can think about making very large changes in the viral genome. We then model those changes to see what would work (and what wouldn’t) before synthesizing the vaccine candidates.

Q: How has computer science changed synthetic biology?

A: Our challenge is to design a virus that's attenuated enough it won’t cause disease, but is still recognized and acted upon by the immune system. We can now shorten this design part to almost an afternoon. The time from thinking about a new vaccine to getting it in a test tube is now less than five months. Classical methods took two to three years.

Q: What are the next big challenges in synthetic biology?...."
http://bit.ly/TdMOEK

by

Michel M. Maharbiz

"The ability to synthesize biological constructs on the scale of the organisms we observe unaided is probably one of the more outlandish, yet recurring, dreams humans have had since they began to modify genes. This review brings together recent developments in synthetic biology, cell and developmental biology, computation, and technological development to provide context and direction for the engineering of rudimentary, autonomous multicellular ensembles."

http://bit.ly/RbGfSV

Computational approaches to predicting essential proteins: a survey http://1.usa.gov/Ufm9Iv

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Petkau-Milroy K, Brunsveld L.

"The regulation of recognition events in nature via dynamic and reversible self-assembly of building blocks has inspired the emergence of supramolecular architectures with similar biological activity. Synthetic molecules of diverse geometries self-assemble in water to target biological systems for applications ranging from imaging and diagnostics, through to drug delivery and tissue engineering. Many of these applications require the ability of the supramolecular system to actively recognize specific cell surface receptors. This molecular recognition is typically achieved with ligands, such as small molecules, peptides, and proteins, which are introduced either prior to or post self-assembly. Advantages of the non-covalent organization of ligands include the responsive nature of the self-assembled structures, the ease of supramolecular synthesis and the possibility to incorporate a multiple array of different ligands through pre-mixing of the building blocks. This review aims to highlight the diversity of self-assembled nanostructures constructed from mono-disperse synthetic building blocks; with a particular focus on their design, self-assembly, functionalization with bioactive ligands and effects thereof on the self-assembly, and possible applications."

http://1.usa.gov/WhXGjg

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By Alexandra Daisy Ginsberg

"Synthetic biology has the potential to transform the manufacturing sector, but it requires a new way of thinking about the relationship between design and science, between nature and industry, and even between creator and product

Design is the transmission of ideas through things. But how do we judge whether new ideas are good things if the designs become invisible? Since the industrial revolution, design has been integral to the process of making things. It translates technology into the mass of useful stuff that marks progress in our everyday lives: the internal combustion engine into the car; the spring into the adjustable lamp; the transistor into the personal computer. Design separates what we make from what already exists: the natural, living stuff we want to control. But design is a plastic term with plastic morals. While we enjoy the conviction that 'to design is to be human', design today is mostly concerned with making products for us to consume, shy of responsibility for the functions to which it gives form and those forms' existence before and beyond their functional lives.

But now the mosquito is becoming a design object. Oxitec's RIDL male mosquitoes progeny die by genetic design. Grown in a factory, sorted by sex and released by the million, they mate with wild female mosquitoes to produce faulty offspring that will never hatch. It is a polite, British design solution to the tricky business of eradicating pathogens, on a geo-engineering scale. Swiss-designed bull sperm are also being trialled, encapsulated in cellulose before being inserted into a cow's uterus, unpackaged at ovulation as her hormones trigger precision-timed conception. Fewer deaths from dengue fever and cheaper dairy products may be the consumer's only experience of these designs. This is death and life as the stuff of design. .."

http://bit.ly/UQZOgS

*Nature Genetics Series: Computational Tools for complex genetic and genomic data*

"The scale and complexity of genetic and genomic data are ever-expanding, requiring biologists to apply increasingly more sophisticated computational tools in the analysis, interpretation and storage of these data. This series contains articles that focus on the application of these software tools in genetics and genomics."

http://bit.ly/T82b2d

by
Michael S. Strano

"DNA is central to the existence of all life on Earth and uniquely encodes the instructions for producing such life. But it has another set of remarkable properties shared by a much larger class of molecules, most of which are yet to be invented. These “chemically sequenced polymers” (CSPs) are built by adding distinct monomers one at a time and can be programmed in such a way as to assemble into arbitrarily complex and three-dimensional shapes. Nature is far ahead of us in the creation and utility of such molecules, but on page 932 of this issue, Langecker et al. (1) provide a glimpse of the structural precision and functionality they offer for programmed assembly."
http://bit.ly/RH5awu