RNA-based temperature sensing is common in bacteria that live in fluctuating environments. Most naturally-occurring RNA thermosensors are heat-inducible, have long sequences, and function by sequestering the ribosome binding site in a hairpin structure at lower temperatures. Here, we demonstrate the de novo design of short, heat-repressible RNA thermosensors. These thermosensors contain a cleavage site for RNase E, an enzyme native to Escherichia coli and many other organisms, in the 5' untranslated region of the target gene. At low temperatures, the cleavage site is sequestered in a stem-loop, and gene expression is unobstructed. At high temperatures, the stem-loop unfolds, allowing for mRNA degradation and turning off expression. We demonstrated that these thermosensors respond specifically to temperature and provided experimental support for the central role of RNase E in the mechanism. We also demonstrated the modularity of these RNA thermosensors by constructing a three-input composite circuit that utilizes transcriptional, post-transcriptional, and post-translational regulation. A thorough analysis of the 24 thermosensors allowed for the development of design guidelines for systematic construction of similar thermosensors in future applications. These short, modular RNA thermosensors can be applied to the construction of complex genetic circuits, facilitating rational reprogramming of cellular processes for synthetic biology applications.
The biosynthesis of benzylisoquinoline alkaloids such as morphine requires tyrosine oxidases, which are prone to overoxidation. A colorimetric readout that co-opts betaxanthin enzymes now enables discovery of an improved oxidase that, with other enzymes, makes reticuline in yeast.
Scientists have built a tiny, long-term memory cell that can both store and process information at the same time, just like the human brain. This is one of the first multi-state electronic memory cells, and it represents a crucial step towards building a bionic brain.
Not only does this new cell - which is 10,000 times thinner than a human hair - open up the potential to store and process way more data than ever before, scientists are even more excited about the fact that it has 'memristive' abilities. This means that it's able to retain remember and be influenced by information that has previously been stored on it - something that our current storage devices aren't capable of.
"This is the closest we have come to creating a brain-like system with memory that learns and stores analog information and is quick at retrieving this stored information," project leader Sharath Sriram, from RMIT University in Australia said in a press release. "The human brain is an extremely complex analog computer ... its evolution is based on its previous experiences, and up until now this functionality has not been able to be adequately reproduced with digital technology."
The cell's new abilities add another dimension beyond the on/off memory cells we currently use to store our data on conventional devices, such as USBs, which are only capable of storing one binary digit (either a 0 or a 1) at a time. The researchers are comparing this to the difference between a regular light switch, which either turns the light on or off, and a dimmer switch, which gives you access to all the shades of light in-between.
"It can give you much more flexibility in terms of what information you store and what functionality you get," one of the researchers, Hussein Nili, told Jessica Kidd over at ABC News.
Publishing in Advanced Functional Materials, the researchers explain that the cells are made out of a functional oxide material in the form of an ultra-thin film. The team created the material last year, and demonstrated that it was highly stable and reliable. But they've now successfully introduced controlled defects into the film, which allow the cell to be influenced by previous events.
(Phys.org) —Two of the most exciting areas of science and technology, synthetic biology and genetic engineering, have just taken a step towards a brave new future in which large-scale synthetic biological circuits composed of bioengineered logic...
Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z, 6-amino-5-nitro-2(1H)-pyridone and P, 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one) that were designed to form a Z:P pair with a standard “edge on” Watson–Crick geometry, but joined by rearranged hydrogen bond donor and acceptor groups. One duplex, with four Z:P pairs, was crystallized with a reverse transcriptase host and adopts primarily a B-form. Another contained six consecutive Z:P pairs; it crystallized without a host in an A-form. In both structures, Z:P pairs fit canonical nucleobase hydrogen-bonding parameters and known DNA helical forms. Unique features include stacking of the nitro group on Z with the adjacent nucleobase ring in the A-form duplex. In both B- and A-duplexes, major groove widths for the Z:P pairs are approximately 1 Å wider than those of comparable G:C pairs, perhaps to accommodate the large nitro group on Z. Otherwise, ZP-rich DNA had many of the same properties as CG-rich DNA, a conclusion supported by circular dichroism studies in solution. The ability of standard duplexes to accommodate multiple and consecutive Z:P pairs is consistent with the ability of natural polymerases to biosynthesize those pairs. This, in turn, implies that the GACTZP synthetic genetic system can explore the entire expanded sequence space that additional nucleotides create, a major step forward in this area of synthetic biology
by Kuntal Mukherjee, Souryadeep Bhattacharyya and Pamela Peralta-Yahya
"A key limitation to engineering microbes for chemical production is a reliance on low-throughput chromatography-based screens for chemical detection. While colorimetric chemicals are amenable to high-throughput screens, many value-added chemicals are not colorimetric and require sensors for high-throughput screening. Here, we use G-protein coupled receptors (GPCRs) known to bind medium-chain fatty acids in mammalian cells to rapidly construct chemical sensors in yeast. Medium-chain fatty acids are immediate precursors to the advanced biofuel fatty acid methyl esters, which can serve as a “drop-in” replacement for D2 diesel. One of the sensors detects even-chain C8–C12 fatty acids with a 13- to 17-fold increase in signal after activation, with linear ranges up to 250 μM. Introduction of a synthetic response unit alters both dynamic and linear range, improving the sensor response to decanoic acid to a 30-fold increase in signal after activation, with a linear range up to 500 μM. To our knowledge, this is the first report of a whole-cell medium-chain fatty acid biosensor, which we envision could be applied to the evolutionary engineering of fatty acid-producing microbes. Given the affinity of GPCRs for a wide range of chemicals, it should be possible to rapidly assemble new biosensors by simply swapping the GPCR sensing unit. These sensors should be amenable to a variety of applications that require different dynamic and linear ranges, by introducing different response units."
The first of a series of three 30 minute videos produced by the American Society for Cybernetics and Change Management Systems, directed by Pille Bunnell, 19...
Socrates Logos's insight:
*A pioneer in biological computing*: *Heinz Förster*
His work focused on cybernetics, the exploration of regulatory systems, and who founded in 1958 the Biological Computer Lab (BCL) at the Department of Electrical Engineering at the University of Illinois. The work of the BCL was focused on the similarities in cybernetic systems and electronics and especially biology inspired computing.
A Muller, K.M
An Unfinished Revolution: Heinz von Foerster and the Biological Computer Laboratory / BCL 1958–1976Vienna Edition Echoraum (2007)
H Foerster, WR Ashby
KE Schaefer (Ed.), Bioastronautics, The Macmillan Co, New York (1964), pp. 333–360
"Despite the many great achievements of computers, no man-made computer can learn from its environment, adapt to its surroundings, spontaneously self-organize, and solve complex problems that require these abilities as well as a biological brain. These abilities arise from the fact that the brain is a complex system capable of emergent behavior, meaning that the system involves interactions between many units resulting in macroscale behavior that cannot be attributed to any individual unit.
Unfortunately, conventional fabrication methods used for today's computers cannot be used to realize complex systems to their full potential due to scaling limits—the methods simply cannot make small enough interconnected units.
Now in a new paper published in Nanotechnology, researchers at UCLA and the National Institute for Materials Science in Japan have developed a method to fabricate a self-organized complex device called an atomic switch network that is in many ways similar to a brain or other natural or cognitive computing device.
"Complex phenomena and self-organization—though ubiquitous in nature, social behavior, and the economy—have never been successfully used in conventional computers for prediction and modelling," James Gimzewski, Chemistry Professor at UCLA, told Phys.org. "The device we have created is capable of rapidly generating self-organization in a small chip with high speed. Furthermore, it bypasses the issue of exponential machine complexity required as a function of problem complexity as in today's computers. Our first steps form the basis for a new type of computation that is urgently needed in our ever increasingly connected world."...."
The programmability of oligonucleotide hybridization offers an attractive platform for the design of assemblies with emergent properties or functions. Developments in DNA nanotechnologies have transformed our thinking about the applications of nucleic acids. Progress from designed assemblies to functional outputs will continue to benefit from functionalities added to the nucleic acids that can participate in reactions or interactions beyond hybridization. In that respect, peptide nucleic acids (PNAs) are interesting because they combine the hybridization properties of DNA with the modularity of peptides. In fact, PNAs form more stable duplexes with DNA or RNA than the corresponding natural homoduplexes. The high stability achieved with shorter oligomers (an 8-mer is sufficient for a stable duplex at room temperature) typically results in very high sequence fidelity in the hybridization with negligible impact of the ionic strength of the buffer due to the lack of electrostatic repulsion between the duplex strands. The simple peptidic backbone of PNA has been shown to be tolerant of modifications with substitutions that further enhance the duplex stability while providing opportunities for functionalization. Moreover, the metabolic stability of PNAs facilitates their integration into systems that interface with biology. Over the past decade, there has been a growing interest in using PNAs as biosupramolecular tags to program assemblies and reactions. A series of robust templated reactions have been developed with functionalized PNA. These reactions can be used to translate DNA templates into functional polymers of unprecedented complexity, fluorescent outputs, or bioactive small molecules. Furthermore, cellular nucleic acids (mRNA or miRNA) have been harnessed to promote assemblies and reactions in live cells. The tolerance of PNA synthesis also lends itself to the encoding of small molecules that can be further assembled on the basis of their nucleic acid sequences. It is now well-established that hybridization-based assemblies displaying two or more ligands can interact synergistically with a target biomolecule. These assemblies have now been shown to be functional in vivo. Similarly, PNA-tagged macromolecules have been used to prepare bioactive assemblies and three-dimensional nanostructures. Several technologies based on DNA-templated synthesis of sequence-defined polymers or DNA-templated display of ligands have been shown to be compatible with reiterative cycles of selection/amplification starting with large libraries of DNA templates, bringing the power of in vitro evolution to synthetic molecules and offering the possibility of exploring uncharted molecular diversity space with unprecedented scope and speed.
Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks1, 2, magnetic systems3, 4, modular robots5, 6 and synthetic molecular systems7, 8, 9 have been devised, such kinematic self-replicators10 are rare compared with examples of theoretical cellular self-replication11, 12, 13, 14, 15, 16, 17, 18. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium19. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition20. Here, we show that DNA T-motifs, which self-assemble into ring structures21, 22, can be designed to self-replicate through toehold-mediated strand displacement reactions23, 24. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication25 and derive a quantitative metric of the self-replicability of the rings.
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